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Sample records for prematurely expressing human

  1. Human milk for the premature infant

    Science.gov (United States)

    Underwood, Mark A.

    2012-01-01

    Synopsis Premature infants are a heterogeneous group with widely differing needs for nutrition and immune protection with risk of growth failure, developmental delays, necrotizing enterocolitis, and late-onset sepsis increasing with decreasing gestational age and birth weight. Human milk from women delivering prematurely has more protein and higher levels of many bioactive molecules compared to milk from women delivering at term. Human milk must be fortified for small premature infants to achieve adequate growth. Mother’s own milk improves growth and neurodevelopment and decreases the risk of necrotizing enterocolitis and late-onset sepsis and should therefore be the primary enteral diet of premature infants. Donor milk is a valuable resource for premature infants whose mothers are unable to provide an adequate supply of milk, but presents significant challenges including the need for pasteurization, nutritional and biochemical deficiencies and a limited supply. PMID:23178065

  2. CONSTRUCTION, EXPRESSION AND PURIFICATION OF RECOMBINANT PRE-MATURE PEPTIDE OF PLANTARICIN F FROM Lactobacillus plantarum S34 IN Escherichia coli

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    Kusdianawati Kusdianawati

    2015-09-01

    Full Text Available Plantaricin is one of bacteriocins that have the potential to be used as food preservative. Plantaricin is safe for human consumption because it can be easily degraded by proteolytic enzymes. The objective of this study was to express and purify recombinant pre-mature peptide of plantaricin F from Lactobacillus plantarum S34 in Escherichia coli. Plantaricin gene-specific primer was used to obtain pln F structural gene amplicon from L. plantarum S34. This amplicon was cloned in pET32a vector and expressed in E. coli BL21 (DE3 pLysS. Pre-mature plantaricin F peptide was expressed as Histagged-fusion protein and separated by Co2+-chelating affinity chromatography. L. plantarum S34-derived pre-mature plantaricin F peptide fused with thioredoxin-(His6tag had successfully been expressed in E. coli BL21 (DE3 pLysS using pET32a as an expression vector. The fused recombinant pln F as pre-mature state expressed had a molecular mass of +24 kDa, meanwhile the fused recombinant that contained only the leader peptide of pln F appeared as +20 kDa based on SDS-PAGE separations. The optimal production of fused recombinant pln F as soluble fraction was obtained when culture condition was added with 0.5 mM of IPTG and incubated at 22°C for 5 hours (OD~1. Furthermore, the expression of fused recombinant pln F as its pre-mature peptide pointed out that the pln F’s leader peptide could be proteolytically cleaved by a system in heterologous cells. Overall, heterologous pln F production as pre-mature peptide fused with thioredoxin-(His6tag had been well established. From this research, we expect plantaricin F can be expressed and purified in E. coli.

  3. DNA-Related Pathways Defective in Human Premature Aging

    OpenAIRE

    Bohr, Vilhelm A.

    2002-01-01

    One of the major issues in studies on aging is the choice of biological model system. The human premature aging disorders represent excellent model systems for the study of the normal aging process, which occurs at a much earlier stage in life in these individuals than in normals. The patients with premature aging also get the age associated diseases at an early stage in life, and thus age associated disease can be studied as well. It is thus of great interest to understand the molecular path...

  4. Group B streptococcus activates transcriptomic pathways related to premature birth in human extraplacental membranes in vitro.

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    Park, Hae-Ryung; Harris, Sean M; Boldenow, Erica; McEachin, Richard C; Sartor, Maureen; Chames, Mark; Loch-Caruso, Rita

    2018-03-01

    Streptococcus agalactiae (group B streptococcus [GBS]) infection in pregnant women is the leading cause of infectious neonatal morbidity and mortality in the United States. Although inflammation during infection has been associated with preterm birth, the contribution of GBS to preterm birth is less certain. Moreover, the early mechanisms by which GBS interacts with the gestational tissue to affect adverse pregnancy outcomes are poorly understood. We hypothesized that short-term GBS inoculation activates pathways related to inflammation and premature birth in human extraplacental membranes. We tested this hypothesis using GBS-inoculated human extraplacental membranes in vitro. In agreement with our hypothesis, a microarray-based transcriptomics analysis of gene expression changes in GBS-inoculated membranes revealed that GBS activated pathways related to inflammation and preterm birth with significant gene expression changes occurring as early as 4 h postinoculation. In addition, pathways related to DNA replication and repair were downregulated with GBS treatment. Conclusions based on our transcriptomics data were further supported by responses of prostaglandin E2 (PGE2), and matrix metalloproteinases 1 (MMP1) and 3 (MMP3), all of which are known to be involved in parturition and premature rupture of membranes. These results support our initial hypothesis and provide new information on molecular targets of GBS infection in human extraplacental membranes.

  5. Human milk: medicine for premature babies.

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    Hilton, Sioned

    2011-12-01

    Following years of research there have been some significant developments in the understanding and subsequent support being offered to Neonatal Intensive Care Unit (NICU) families. In addition, ground breaking advances in the treatment of premature infants, with specific interest in the role of human milk, are now available. New information was presented by leading international researcher, Professor Meier, at an international symposium earlier this year. This article seeks to share this insightful information and provide support to those working in or around the NICU.

  6. Human parechovirus type 3 infection: Cause of apnea in infants born prematurely.

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    Nirei, Jun; Aizawa, Yuta; Okazaki, Minoru; Kobayashi, Akira; Onozuka, Junya; Numata, Osamu; Oishi, Tomohiro; Saitoh, Akihiko

    2016-05-01

    Four infants born prematurely presented with multiple apnea episodes caused by human parechovirus type 3 (HPeV3) infection. All patients required oxygen supplementation, and one patient required mechanical ventilation. HPeV3 infection might be included in the differential diagnosis of apnea in neonates and young infants, especially those born prematurely. © 2016 Japan Pediatric Society.

  7. Chronic Low Dose Rate Ionizing Radiation Exposure Induces Premature Senescence in Human Fibroblasts that Correlates with Up Regulation of Proteins Involved in Protection against Oxidative Stress

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    Olga Loseva

    2014-07-01

    Full Text Available The risks of non-cancerous diseases associated with exposure to low doses of radiation are at present not validated by epidemiological data, and pose a great challenge to the scientific community of radiation protection research. Here, we show that premature senescence is induced in human fibroblasts when exposed to chronic low dose rate (LDR exposure (5 or 15 mGy/h of gamma rays from a 137Cs source. Using a proteomic approach we determined differentially expressed proteins in cells after chronic LDR radiation compared to control cells. We identified numerous proteins involved in protection against oxidative stress, suggesting that these pathways protect against premature senescence. In order to further study the role of oxidative stress for radiation induced premature senescence, we also used human fibroblasts, isolated from a patient with a congenital deficiency in glutathione synthetase (GS. We found that these GS deficient cells entered premature senescence after a significantly shorter time of chronic LDR exposure as compared to the GS proficient cells. In conclusion, we show that chronic LDR exposure induces premature senescence in human fibroblasts, and propose that a stress induced increase in reactive oxygen species (ROS is mechanistically involved.

  8. The role of the human leukocyte antigen system in retinopathy of prematurity: a pilot study.

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    Flor-de-Lima, Filipa; Rocha, Gustavo; Proença, Elisa; Tafulo, Sandra; Freitas, Fátima; Guimarães, Hercília

    2013-12-01

    To assess the association between the human leukocyte antigen system and retinopathy of prematurity. Neonates of prematurity. A large-scale population-based study should be performed to clarify this association. ©2013 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  9. Innate Immunity and Human Milk MicroRNAs Content: A New Perspective for Premature Newborns

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    Erika Cione

    2017-02-01

    Full Text Available Context The premature newborns are prone to develop both early onset and late onset neonatal sepsis. The major causes of this phenomenon rely on the immaturity of the immune system, which has reduced capability to respond adequately to pathogens. Evidence Acquisition Titles and abstracts of previous papers were scanned before reading the full-text, in order to retrieve appropriate information. The databases used for searching were PubMed, Cochrane, and Embase for articles published before 1st of July, 2016. Secondary search for articles cited in reference lists were identified by the primary search. This review focused on neonatal sepsis incidence and the associated immune response with regards to microRNAs of human milk as a new microelement that enables regulation of innate immunity functions. Results Since human milk is a valuable source of microRNAs, a better understanding of its content will open a new therapeutic avenue for the clinical management of infectious diseases affecting premature newborns. The variation in miRNAs quantity in human milk needs to be considered. Mother’s milk can have different amounts of miRNAs and the identification of a microMilk batch richer of miRNAs can be a nutrition intervention method for modulating innate immunity in clinical management of premature newborns. Conclusions Routine translation of the microMilk concept for neonatal intensive care unit (NICU, in the management of premature newborns could be a way of defending premature newborns and Very Low Birth Weight (VLBW infants from both early and late sepsis.

  10. Association between human breast milk and retinopathy of prematurity.

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    Fonseca, Luciana Teixeira; Senna, Denise C; Eckert, Gabriela Unchalo; Silveira, Rita de Cássia; Procianoy, Renato Soibelmann

    2018-04-01

    To evaluate the possible protective effect of breast milk against retinopathy of prematurity by comparing the amount of breast milk received by patients who developed retinopathy of prematurity and those who did not and to determine both the required minimum amount of breast milk and the time of life during which neonates need to receive breast milk for this effect to be significant. Cohort study of newborns with a birth weight of prematurity of any degree was 31% (100 of 323 patients) and that of severe retinopathy of prematurity was of 9% (29 of 323 patients). The median amounts of breast milk received daily by patients with and without retinopathy of prematurity were 4.9 mL/kg (interquartile range, 0.3-15.4) and 10.2 mL/kg (1.5-25.5), respectively. The amount of breast milk received in the first 6 weeks of life was inversely associated with the incidence of both retinopathy of prematurity of any degree and severe retinopathy of prematurity in the univariate analyses. However, the statistical significance was maintained only during the sixth week of life in a per-period multivariate analysis controlling for confounding factors. Small amounts of breast milk are inadequate to prevent retinopathy of prematurity in premature newborns at risk for the disease.

  11. Human cytomegalovirus infections in premature infants by ...

    African Journals Online (AJOL)

    Freezing breast milk may be protective for the preterm infant until the titer of CMV antibody increases. However clinical importance of CMV infection in premature infants by breast-feeding is still unclear. This minireview focuses on recent advances in the study of CMV infection in premature infants by breastfeeding.

  12. Feeding premature neonate

    DEFF Research Database (Denmark)

    Dam, Mie S.; Juhl, Sandra M.; Sangild, Per T.

    2017-01-01

    Kinship, understood as biogenetic proximity, between a chosen animal model and a human patient counterpart, is considered essential to the process of ‘translating’ research from the experimental animal laboratory to the human clinic. In the Danish research centre, NEOMUNE, premature piglets are fed...... a novel milk diet (bovine colostrum) to model the effects of this new diet in premature infants. Our ethnographic fieldwork in an experimental pig laboratory and a neonatal intensive care unit (NICU) in 2013–2014 shows that regardless of biogenetics, daily practices of feeding, housing, and clinical care...... the researchers refer to as the ‘translatability’ of the results. In the NICU, parents of premature infants likewise imagine a kind of interspecies kinship when presented with the option to supplement mother's own milk with bovine colostrum for the first weeks after birth. However, in this setting the NICU...

  13. Human Metapneumovirus Infection is Associated with Severe Respiratory Disease in Preschool Children with History of Prematurity.

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    Pancham, Krishna; Sami, Iman; Perez, Geovanny F; Huseni, Shehlanoor; Kurdi, Bassem; Rose, Mary C; Rodriguez-Martinez, Carlos E; Nino, Gustavo

    2016-02-01

    Human metapneumovirus (HMPV) is a recently discovered respiratory pathogen of the family Paramyxoviridae, the same family as that of respiratory syncytial virus (RSV). Premature children are at high risk of severe RSV infections, however, it is unclear whether HMPV infection is more severe in hospitalized children with a history of severe prematurity. We conducted a retrospective analysis of the clinical respiratory presentation of all polymerase chain reaction-confirmed HMPV infections in preschool-age children (≤5 years) with and without history of severe prematurity (prematurity. Preschool children with a history of prematurity had more severe HMPV disease as illustrated by longer hospitalizations, new or increased need for supplemental O2, and higher severity scores independently of age, ethnicity, and history of asthma. Our study suggests that HMPV infection causes significant disease burden among preschool children with a history of prematurity leading to severe respiratory infections and increasing health care resource utilization due to prolonged hospitalizations. Copyright © 2016. Published by Elsevier B.V.

  14. Multimodel estimates of premature human mortality due to intercontinental transport of air pollution

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    Liang, C.; Silva, R.; West, J. J.; Sudo, K.; Lund, M. T.; Emmons, L. K.; Takemura, T.; Bian, H.

    2015-12-01

    Numerous modeling studies indicate that emissions from one continent influence air quality over others. Reducing air pollutant emissions from one continent can therefore benefit air quality and health on multiple continents. Here, we estimate the impacts of the intercontinental transport of ozone (O3) and fine particulate matter (PM2.5) on premature human mortality by using an ensemble of global chemical transport models coordinated by the Task Force on Hemispheric Transport of Air Pollution (TF HTAP). We use simulations of 20% reductions of all anthropogenic emissions from 13 regions (North America, Central America, South America, Europe, Northern Africa, Sub-Saharan Africa, Former Soviet Union, Middle East, East Asia, South Asia, South East Asia, Central Asia, and Australia) to calculate their impact on premature mortality within each region and elsewhere in the world. To better understand the impact of potential control strategies, we also analyze premature mortality for global 20% perturbations from five sectors individually: power and industry, ground transport, forest and savannah fires, residential, and others (shipping, aviation, and agriculture). Following previous studies, premature human mortality resulting from each perturbation scenario is calculated using a health impact function based on a log-linear model for O3 and an integrated exposure response model for PM2.5 to estimate relative risk. The spatial distribution of the exposed population (adults aged 25 and over) is obtained from the LandScan 2011 Global Population Dataset. Baseline mortality rates for chronic respiratory disease, ischemic heart disease, cerebrovascular disease, chronic obstructive pulmonary disease, and lung cancer are estimated from the GBD 2010 country-level mortality dataset for the exposed population. Model results are regridded from each model's original grid to a common 0.5°x0.5° grid used to estimate mortality. We perform uncertainty analysis and evaluate the sensitivity

  15. Promising markers for the detection of premature senescence tumor cells induced by ionizing radiation: Cathepsin D and eukaryotic translation elongation factor 1

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    Byun, Hae-Ok; Han, Na-Kyung; Lee, Jae-Seon [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2008-05-15

    Recently, it has been proved that induction of senescence could be a promising way of tumor treatment. Senescence was originally described in normal human cells undergoing a finite number of divisions before permanent growth arrest. It has now become regarded more broadly as a general biological program of terminal growth arrest. A variety of stresses such as ionizing radiation (IR), oxidative stress, oncogenic transformation, DNA damaging agents triggers stress-induced premature senescence, i.e. rapid and permanent cell growth arrest. Therefore, premature senescence is bona fide barrier to tumorigenesis and hallmark of premalignant tumors. However, there is lack of obvious markers for senescent tumor cells. To identify useful premature senescence markers for tumor cells, we monitored the changes of protein expression profile in IR-induced premature senescence MCF7 human breast cancer cells. We identified biomarkers which evidently changed their expression levels in ionizing radiation-induced senescenct tumor cells.

  16. Promising markers for the detection of premature senescence tumor cells induced by ionizing radiation: Cathepsin D and eukaryotic translation elongation factor 1

    International Nuclear Information System (INIS)

    Byun, Hae-Ok; Han, Na-Kyung; Lee, Jae-Seon

    2008-01-01

    Recently, it has been proved that induction of senescence could be a promising way of tumor treatment. Senescence was originally described in normal human cells undergoing a finite number of divisions before permanent growth arrest. It has now become regarded more broadly as a general biological program of terminal growth arrest. A variety of stresses such as ionizing radiation (IR), oxidative stress, oncogenic transformation, DNA damaging agents triggers stress-induced premature senescence, i.e. rapid and permanent cell growth arrest. Therefore, premature senescence is bona fide barrier to tumorigenesis and hallmark of premalignant tumors. However, there is lack of obvious markers for senescent tumor cells. To identify useful premature senescence markers for tumor cells, we monitored the changes of protein expression profile in IR-induced premature senescence MCF7 human breast cancer cells. We identified biomarkers which evidently changed their expression levels in ionizing radiation-induced senescenct tumor cells

  17. Digestion of Human Milk Oligosaccharides by Bifidobacterium breve in the Premature Infant.

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    Underwood, Mark A; Davis, Jasmine C C; Kalanetra, Karen M; Gehlot, Sanjay; Patole, Sanjay; Tancredi, Daniel J; Mills, David A; Lebrilla, Carlito B; Simmer, Karen

    2017-10-01

    The aim of this study was to measure consumption and absorption of human milk oligosaccharides (HMOs) in a cohort of premature infants treated with probiotic Bifidobacterium breve. Twenty-nine premature infants (median gestational age 28 weeks, range 23-32 weeks) cared for in the neonatal intensive care unit of the King Edward and Princess Margaret Hospital in Perth, Australia, were treated with B breve at a dose of 1.66 billion organisms per day. Samples of feces, urine, and milk were obtained at initiation of the probiotic and again 3 weeks later. 16S ribosomal RNA from the feces was analyzed by next-generation sequencing. Quantitation of HMO content of the milk, urine, and feces was performed using nano-high-performance liquid chromatography-chip/time-of-flight mass spectrometry. There was heterogeneity in colonization with bifidobacteria. "Responders" received milk with higher percentages of fucosylated HMOs and had higher percentages of bifidobacteria and lower percentages of Enterobacteriaceae in their feces than "nonresponders." Several individual HMOs in the milk were associated with changes in fecal bifidobacteria over time. Changes over time in milk, fecal, and urine HMOs suggested heterogeneity among HMO structures in consumption by microbes in the gut lumen and absorption from the intestine. Colonization of the premature infant intestinal tract with probiotic B breve is influenced by prebiotic HMOs. B breve is a selective consumer of HMOs in the premature infant.

  18. From the Hayflick mosaic to the mosaics of ageing. Role of stress-induced premature senescence in human ageing.

    Science.gov (United States)

    Toussaint, Olivier; Remacle, Jose; Dierick, Jean-François; Pascal, Thierry; Frippiat, Christophe; Zdanov, Stéphanie; Magalhaes, Joao Pedro; Royer, Véronique; Chainiaux, Florence

    2002-11-01

    The Hayflick limit-senescence of proliferative cell types-is a fundamental feature of proliferative cells in vitro. Various human proliferative cell types exposed in vitro to many types of subcytotoxic stresses undergo stress-induced premature senescence (SIPS) (also called stress-induced premature senescence-like phenotype, according to the definition of senescence). The known mechanisms of appearance the main features of SIPS are reviewed: senescent-like morphology, growth arrest, senescence-related changes in gene expression, telomere shortening. Long before telomere-shortening induces senescence, other factors such as culture conditions or lack of 'feeder cells' can trigger either SIPS or prolonged reversible G(0) phase of the cell cycle. In vivo, 'proliferative' cell types of aged individuals are likely to compose a mosaic made of cells irreversibly growth arrested or not. The higher level of stress to which these cells have been exposed throughout their life span, the higher proportion of the cells of this mosaic will be in SIPS rather than in telomere-shortening dependent senescence. All cell types undergoing SIPS in vivo, most notably the ones in stressful conditions, are likely to participate in the tissular changes observed along ageing. For instance, human diploid fibroblasts (HDFs) exposed in vivo and in vitro to pro-inflammatory cytokines display biomarkers of senescence and might participate in the degradation of the extracellular matrix observed in ageing.

  19. Expression of selected genes in preterm premature rupture of fetal membranes.

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    Kuć, Paweł; Laudański, Piotr; Kowalczuk, Oksana; Chyczewski, Lech; Laudański, Tadeusz

    2012-08-01

    To analyse the expression of 15 genes encoding receptors and enzymes associated with the molecular mechanism of the tocolytic drugs atosiban (oxytocin receptor antagonist), nifedipine (calcium channel blocker) and celecoxib (selective cyclo-oxygenase-2 inhibitor) in preterm labor patients with premature rupture of fetal membranes in relation to symptoms of intrauterine infection and preterm labor risk factors. Experimental molecular study. Tertiary obstetric care center. Myometrial samples were obtained during cesarean sections from 35 patients who delivered preterm with unverified symptoms of intrauterine infection, 35 patients who delivered preterm without symptoms of intrauterine infection and 90 women who delivered at term. The Micro Fluidic Profiling Card analytic system was used to evaluate mRNA expression of the genes of interest. The relative quantification values for mRNA expression. The median oxytocin receptor and cyclo-oxygenase-2 mRNA expression in preterm patients with clinical symptoms of intrauterine infection was significantly higher than in preterm patients without symptoms. The median mRNA expression of β(1) , β(3) and β(4) subunits of the L-type calcium channel and prostaglandin E(2) receptor was significantly higher in preterm patients compared with term patients. The mRNA expression of hormones, enzymes and their receptors associated with tocolytic actions can differ in various clinical conditions. The expression of these genes is regulated at different levels and can be modified by inflammatory factors, which affect their functions. © 2012 The Authors Acta Obstetricia et Gynecologica Scandinavica© 2012 Nordic Federation of Societies of Obstetrics and Gynecology.

  20. Proteome oxidative carbonylation during oxidative stress-induced premature senescence of WI-38 human fibroblasts

    DEFF Research Database (Denmark)

    Le Boulch, Marine; Ahmed, Emad K; Rogowska-Wrzesinska, Adelina

    2018-01-01

    Accumulation of oxidatively damaged proteins is a hallmark of cellular and organismal ageing, and is also a phenotypic feature shared by both replicative senescence and stress-induced premature senescence of human fibroblasts. Moreover, proteins that are building up as oxidized (i.e. the "Oxi-pro...

  1. Adolescent Premature Ovarian Insufficiency Following Human Papillomavirus Vaccination

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    Deirdre Therese Little MBBS, DRANZCOG, FACRRM

    2014-10-01

    Full Text Available Three young women who developed premature ovarian insufficiency following quadrivalent human papillomavirus (HPV vaccination presented to a general practitioner in rural New South Wales, Australia. The unrelated girls were aged 16, 16, and 18 years at diagnosis. Each had received HPV vaccinations prior to the onset of ovarian decline. Vaccinations had been administered in different regions of the state of New South Wales and the 3 girls lived in different towns in that state. Each had been prescribed the oral contraceptive pill to treat menstrual cycle abnormalities prior to investigation and diagnosis. Vaccine research does not present an ovary histology report of tested rats but does present a testicular histology report. Enduring ovarian capacity and duration of function following vaccination is unresearched in preclinical studies, clinical and postlicensure studies. Postmarketing surveillance does not accurately represent diagnoses in adverse event notifications and can neither represent unnotified cases nor compare incident statistics with vaccine course administration rates. The potential significance of a case series of adolescents with idiopathic premature ovarian insufficiency following HPV vaccination presenting to a general practice warrants further research. Preservation of reproductive health is a primary concern in the recipient target group. Since this group includes all prepubertal and pubertal young women, demonstration of ongoing, uncompromised safety for the ovary is urgently required. This matter needs to be resolved for the purposes of population health and public vaccine confidence.

  2. Human milk reduces outpatient upper respiratory symptoms in premature infants during their first year of life.

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    Blaymore Bier, Jo-Ann; Oliver, Tanya; Ferguson, Anne; Vohr, Betty R

    2002-01-01

    To determine if ingestion of human milk after discharge reduces symptoms of infections in premature infants. Follow-up of 39 infants with birth weights milk and 15 of whom received only formula after discharge, was carried out. Mothers were given a calendar on which they recorded any signs of infections and feeding and day-care information. Data were collected at 1 month after discharge and at 3, 7, and 12 months corrected age. Results show no differences between groups in birth weight, gestation, gender, maternal age, parental tobacco use, number of siblings, and day-care attendance. Socioeconomic status score was higher in the human milk group. Infants who received human milk had fewer days of upper respiratory symptoms at 1 month after discharge (pmilk post discharge is associated with a reduction of upper respiratory symptoms in premature infants during their first year of life.

  3. Targeting VEGF in canine oxygen-induced retinopathy - a model for human retinopathy of prematurity.

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    McLeod, D Scott; Lutty, Gerard A

    2016-01-01

    Development of the dog superficial retinal vasculature is similar to the mechanism of human retinal vasculature development; they both develop by vasculogenesis, differentiation, and assembly of vascular precursors called angioblasts. Canine oxygen-induced retinopathy (OIR) was first developed by Arnall Patz in an effort to experimentally determine the effects of hyperoxia on the development of the retinal vasculature. The canine OIR model has many characteristics in common with human retinopathy of prematurity. Exposure of 1-day-old dogs to hyperoxia for 4 days causes a vaso-obliteration throughout the retina. Vasoproliferation, after the animals have returned to room air, is robust. The initial small preretinal neovascular formations anastomose to form large preretinal membranes that eventually cause tractional retinal folds. The end-stage pathology of the canine model is similar to stage IV human retinopathy of prematurity. Therefore, canine OIR is an excellent forum to evaluate the response to drugs targeting VEGF and its receptors. Evaluation of an antibody to VEGF-R2 and the VEGF-Trap demonstrated that doses should be titered down so that preretinal neovascularization is inhibited but retinal revascularization is able to proceed, vascularizing peripheral retina and preventing it from being a source of VEGF.

  4. Altered expressions of endothelial junction protein of placental capillaries in premature infants with intraventricular hemorrhage

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    Maria Ekawati

    2016-10-01

    Full Text Available Background: Placental hypoxia may lead to oxidative stress, which inflicts damage to capillary protein junction. The aim of this study was to evaluate altered expression of endothelial junction protein of capillaries in hypoxia condition and to observe its correlation with the incidence of  intraventricular hemorrhage in premature infants.Methods: A cross-sectional study was conducted by using placental tissues of premature infants as amodel of capillary integrity (29 hypoxic and 29 non-hypoxic. Hypoxia inducible factor (HIF-1α was measured to define placental tissue response to hypoxia; malondialdehyde (MDA and glutathione (GSH served as markers of oxidative stress. The expressions of junctional proteins, N-cadherin and occludin were analyzed by immunohistochemistry. Intraventricular hemorrhage (IVH was detected by cranial ultrasound at the third day. Unpaired t test, Mann-Whitney, and Chi-square tests were used to analyze the data.Results: The HIF-1α and MDA levels were slightly, but not significantly, higher in hypoxia group {13.64±8.70 pg/mg protein and 10.31 pmol/mg tissue (ranged 1.92–93.61, respectively}  compared to non- hypoxia group {10.65±5.35 pg/mg protein and 9.77 pmol/mg tissue (ranged 2.42–93.31}. GSH levels were not different in both groups (38.14 (ranged 9.44–118.91 and  38.47(ranged 16.49–126.76 ng/mg protein, respectively. mRNA expression of N-cadherin (0.13 and occludin (0.096 were significantly lower in hypoxia comparedto non-hypoxia group (p=0,001, while protein expression of  N-cadherin (3.4; 75.9; 6.9; 13.8% and occludin  (20.7; 3.4; 69.0; 3.4; 6.9%  in hypoxia group was not associated with IVH (p=0.783 and p=0.743.Conclusion: Hypoxia altered expression of endothelial junction protein in placental capillaries, but no association with intraventricular hemorrhage was observed.

  5. Dose response curve for prematurely condensed chromosome fragments of human lymphocytes after 60Co-γ ray exposure

    International Nuclear Information System (INIS)

    Gao Jinsheng; Zheng Siying; Bao Hong

    1992-06-01

    The dose-effect relationship of premature condensed chromosome fragments in human lymphocytes irradiated by 60 Co gamma ray was studied by PCC method (premature condensed chromosomes). In addition, The conventional cellular genetics method was also used in the study. The response curve of both methods can represented by two linear equations. The ratio of two slopes, K PCC /K M1 , is about 28. Comparing with conventional method, the PCC method has many advantages such as faster, simpler, more sensitive and accurate. The PCC method used in the studying of radiation damage is also discussed

  6. [Macronutrients and energy in milk from mothers of premature infants].

    Science.gov (United States)

    He, Bi-Zi; Sun, Xiu-Jing; Quan, Mei-Ying; Wang, Dan-Hua

    2014-07-01

    To study the dynamic changes in macronutrients and energy in human milk from mothers of premature infants. A total of 339 human milk samples were collected from 170 women who delivered preterm or full-term infants in the Department of Obstetrics and Gynecology, Peking Union Medical College Hospital between November 2012 and January 2014. Macronutrients (proteins, fats and carbohydrates and energy were measured using a MIRIS human milk analyzer and compared between groups. In milk samples from premature infants' mothers, the protein levels were the highest in colostrum (2.22±0.49 g/dL), less in transitional milk (1.83±0.39 g/dL), and the least in mature milk (1.40±0.28 g/dL) (Pmacronutrients and energy in milk from mothers of premature infants vary significantly between colostrum, transitional milk, and mature milk. Protein levels are significantly higher in colostrum from premature infants' mothers than in colostrum from term infants' mothers, but the significant difference is not seen for mature milk. Macronutrient and energy levels show significant differences between milk samples from mothers of premature infants with different gestational ages, so as to meet different needs of premature infants.

  7. MicroRNA Regulation of Ionizing Radiation-Induced Premature Senescence

    International Nuclear Information System (INIS)

    Wang Yong; Scheiber, Melissa N.; Neumann, Carola; Calin, George A.; Zhou Daohong

    2011-01-01

    Purpose: MicroRNAs (miRNAs) have emerged as critical regulators of many cellular pathways. Ionizing radiation (IR) exposure causes DNA damage and induces premature senescence. However, the role of miRNAs in IR-induced senescence has not been well defined. Thus, the purpose of this study was to identify and characterize senescence-associated miRNAs (SA-miRNAs) and to investigate the role of SA-miRNAs in IR-induced senescence. Methods and Materials: In human lung (WI-38) fibroblasts, premature senescence was induced either by IR or busulfan (BU) treatment, and replicative senescence was accomplished by serial passaging. MiRNA microarray were used to identify SA-miRNAs, and real-time reverse transcription (RT)-PCR validated the expression profiles of SA-miRNAs in various senescent cells. The role of SA-miRNAs in IR-induced senescence was characterized by knockdown of miRNA expression, using anti-miRNA oligonucleotides or by miRNA overexpression through the transfection of pre-miRNA mimics. Results: We identified eight SA-miRNAs, four of which were up-regulated (miR-152, -410, -431, and -493) and four which were down-regulated (miR-155, -20a, -25, and -15a), that are differentially expressed in both prematurely senescent (induced by IR or BU) and replicatively senescent WI-38 cells. Validation of the expression of these SA-miRNAs indicated that down-regulation of miR-155, -20a, -25, and -15a is a characteristic miRNA expression signature of cellular senescence. Functional analyses revealed that knockdown of miR-155 or miR-20a, but not miR-25 or miR-15a, markedly enhanced IR-induced senescence, whereas ectopic overexpression of miR-155 or miR-20a significantly inhibited senescence induction. Furthermore, our studies indicate that miR-155 modulates IR-induced senescence by acting downstream of the p53 and p38 mitogen-activated protein kinase (MAPK) pathways and in part via regulating tumor protein 53-induced nuclear protein 1 (TP53INP1) expression. Conclusion: Our

  8. Different therapeutic effects of cells derived from human amniotic membrane on premature ovarian aging depend on distinct cellular biological characteristics.

    Science.gov (United States)

    Ding, Chenyue; Li, Hong; Wang, Yun; Wang, Fuxin; Wu, Huihua; Chen, Rulei; Lv, Jinghuan; Wang, Wei; Huang, Boxian

    2017-07-27

    Many reports have shown that various kinds of stem cells have the ability to recover premature ovarian aging (POA) function. Transplantation of human amniotic epithelial cells (hAECs) improves ovarian function damaged by chemotherapy in a mice model. Understanding of how to evaluate the distinct effects of adult stem cells in curing POA and how to choose stem cells in clinical application is lacking. To build a different degrees of POA model, mice were administered different doses of cyclophosphamide: light dose (70 mg/kg, 2 weeks), medium dose (70 mg/kg, 1 week; 120 mg/kg, 1 week), and high dose (120 mg/kg, 2 weeks). Enzyme-linked immunosorbent assay detected serum levels of sex hormones, and hematoxylin and eosin staining allowed follicle counting and showed the ovarian tissue structure. DiIC 18 (5)-DS was employed to label human amniotic mesenchymal stem cells (hAMSCs) and hAECs for detecting the cellular retention time in ovaries by a live imaging system. Proliferation of human ovarian granule cells (ki67, AMH, FSHR, FOXL2, and CYP19A1) and immunological rejection of human peripheral blood mononuclear cells (CD4, CD11b, CD19, and CD56) were measured by flow cytometry (fluorescence-activated cell sorting (FACS)). Distinction of cellular biological characteristics between hAECs and hAMSCs was evaluated, such as collagen secretory level (collagen I, II, III, IV, and VI), telomerase activity, pluripotent markers tested by western blot, expression level of immune molecules (HLA-ABC and HLA-DR) analyzed by FACS, and cytokines (growth factors, chemotactic factors, apoptosis factors, and inflammatory factors) measured by a protein antibody array methodology. After hAMSCs and hAECs were transplanted into a different degrees of POA model, hAMSCs exerted better therapeutic activity on mouse ovarian function in the high-dose administration group, promoting the proliferation rate of ovarian granular cells from premature ovarian failure patients, but also provoking immune

  9. Premature menopause.

    Science.gov (United States)

    Okeke, Tc; Anyaehie, Ub; Ezenyeaku, Cc

    2013-01-01

    Premature menopause affects 1% of women under the age of 40 years. The women are at risk of premature death, neurological diseases, psychosexual dysfunction, mood disorders, osteoporosis, ischemic heart disease and infertility. There is need to use simplified protocols and improved techniques in oocyte donation to achieve pregnancy and mother a baby in those women at risk. Review of the pertinent literature on premature menopause, selected references, internet services using the PubMed and Medline databases were included in this review. In the past, pregnancy in women with premature menopause was rare but with recent advancement in oocyte donation, women with premature menopause now have hoped to mother a child. Hormone replacement therapy is beneficial to adverse consequences of premature menopause. Women with premature menopause are at risk of premature death, neurological diseases, psychosexual dysfunction, mood disorders, osteoporosis, ischemic heart disease and infertility. Public enlightenment and education is important tool to save those at risk.

  10. Epigenetic regulation of lncRNA connects ubiquitin-proteasome system with infection-inflammation in preterm births and preterm premature rupture of membranes.

    Science.gov (United States)

    Luo, Xiucui; Pan, Jing; Wang, Leilei; Wang, Peirong; Zhang, Meijiao; Liu, Meilin; Dong, Ziqing; Meng, Qian; Tao, Xuguang; Zhao, Xinliang; Zhong, Julia; Ju, Weina; Gu, Yang; Jenkins, Edmund C; Brown, W Ted; Shi, Qingxi; Zhong, Nanbert

    2015-02-15

    Preterm premature rupture of membranes (PPROM) is responsible for one third of all preterm births (PTBs). We have recently demonstrated that long noncoding RNAs (lncRNAs) are differentially expressed in human placentas derived from PPROM, PTB, premature rupture of the membranes (PROM), and full-term birth (FTB), and determined the major biological pathways involved in PPROM. Here, we further investigated the relationship of lncRNAs, which are differentially expressed in spontaneous PTB (sPTB) and PPROM placentas and are found to overlap a coding locus, with the differential expression of transcribed mRNAs at the same locus. Ten lncRNAs (five up-regulated and five down-regulated) and the lncRNA-associated 10 mRNAs (six up- and four down-regulated), which were identified by microarray in comparing PPROM vs. sPTB, were then validated by real-time quantitative PCR. A total of 62 (38 up- and 24 down-regulated) and 1,923 (790 up- and 1,133 down-regulated) lncRNAs were identified from placentas of premature labor (sPTB + PPROM), as compared to those from full-term labor (FTB + PROM) and from premature rupture of membranes (PPROM + PROM), as compared to those from non-rupture of membranes (sPTB + FTB), respectively. We found that a correlation existed between differentially expressed lncRNAs and their associated mRNAs, which could be grouped into four categories based on the gene strand (sense or antisense) of lncRNA and its paired transcript. These findings suggest that lncRNA regulates mRNA transcription through differential mechanisms. Differential expression of the transcripts PPP2R5C, STAM, TACC2, EML4, PAM, PDE4B, STAM, PPP2R5C, PDE4B, and EGFR indicated a co-expression among these mRNAs, which are involved in the ubiquitine-proteasome system (UPS), in addition to signaling transduction and beta adrenergic signaling, suggesting that imbalanced regulation of UPS may present an additional mechanism underlying the premature rupture of membrane in PPROM

  11. Targeting VEGF in canine oxygen-induced retinopathy - a model for human retinopathy of prematurity

    Directory of Open Access Journals (Sweden)

    McLeod DS

    2016-05-01

    Full Text Available D Scott McLeod, Gerard A Lutty Department of Ophthalmology, Wilmer Ophthalmological Institute, Johns Hopkins Hospital, Baltimore, MD, USA Abstract: Development of the dog superficial retinal vasculature is similar to the mechanism of human retinal vasculature development; they both develop by vasculogenesis, differentiation, and assembly of vascular precursors called angioblasts. Canine oxygen-induced retinopathy (OIR was first developed by Arnall Patz in an effort to experimentally determine the effects of hyperoxia on the development of the retinal vasculature. The canine OIR model has many characteristics in common with human retinopathy of prematurity. Exposure of 1-day-old dogs to hyperoxia for 4 days causes a vaso-obliteration throughout the retina. Vasoproliferation, after the animals have returned to room air, is robust. The initial small preretinal neovascular formations anastomose to form large preretinal membranes that eventually cause tractional retinal folds. The end-stage pathology of the canine model is similar to stage IV human retinopathy of prematurity. Therefore, canine OIR is an excellent forum to evaluate the response to drugs targeting VEGF and its receptors. Evaluation of an antibody to VEGF-R2 and the VEGF-Trap demonstrated that doses should be titered down so that preretinal neovascularization is inhibited but retinal revascularization is able to proceed, vascularizing peripheral retina and preventing it from being a source of VEGF. Keywords: angioblasts, blood vessels, endothelial cells, oxygen, retinopathy, retina, vascular endothelial cell growth factor

  12. Premature chromosome condensation following x irradiation of mammalian cells: expression time and dose-response

    International Nuclear Information System (INIS)

    Griffiths, T.D.; Carpenter, J.G.

    1979-01-01

    Premature chromosome condensation (PCC) in Chinese hamster ovary (CHO) cells following exposure to 300-kVp x rays was first detected in the mitosis that followed the second postirradiation S phase. Thus, cells irradiated in G1 first expressed PCC at the second postirradiation mitosis while cells irradiated in G2 did not express PCC until the third postirradiation mitosis. Cells irradiated in the S phase expressed PCC at the second postirradiation mitosis with a frequency that was related to the position of the cells in the S phase at the time of exposure, cells in the first half of the S phase (at the time of exposure) showing a higher frequency than cells positioned in the second half. Thus, DNA replication during the first postirradiation S phase may be involved in the processing of lesions that eventually give rise to PCC. For cells in G1 at the time of exposure, the D/sub o/ for PCC expression at the second postirradiation mitosis was around 825 rad, indicating that PCC may play only a minor role in x-ray-induced cell killing. Autoradiographic analysis indicated approximately 50% of the PCC patches scored were replicating DNA at the time condensation was attempted. Daughter cells derived from such cells would suffer loss of genetic material

  13. [Breast is best--human milk for premature infants].

    Science.gov (United States)

    Riskin, Arieh; Bader, David

    2003-03-01

    Nutrition for preterm babies is aimed at achieving expected intrauterine growth and accretion of nutrients. Early trophic feedings should be started as soon as possible for gastrointestinal priming. Mother's (breast) milk is the best food for preterm babies. Its advantages are in host defence, nutritional components and suitability for gut absorption, as well as its psychological and developmental value. The limitations of human milk for preterm babies, mainly in protein and minerals, can be compensated for by using powdered human milk fortifier. Sucking skills usually mature around 34 weeks, corrected gestational age. Thus, small preemies are initially fed by orogastric tubes, meaning that expressed breast milk is used. Support of lactation in mothers of preemies mandates protection of the mother and child bonding process and early skin to skin contact ("kangeroo care"). Methods for storage of expressed breast milk and the recommended length of storage are discussed. Milk bank mandates pasteurization and freezing of the donors' milk. Most of the nutritional and immunological advantages of human milk are preserved after such treatments. Cytomegalovirus (CMV) infections in preterm infants, that were acquired from mother's expressed breast milk, are not uncommon, and require further attention.

  14. Proteomic and metabolomic analysis of H2O2-induced premature senescent human mesenchymal stem cells.

    Science.gov (United States)

    Kim, Ji-Soo; Kim, Eui-Jin; Kim, Hyun-Jung; Yang, Ji-Young; Hwang, Geum-Sook; Kim, Chan-Wha

    2011-06-01

    Stress induced premature senescence (SIPS) occurs after exposure to many different sublethal stresses including H(2)O(2), hyperoxia, or tert-butylhydroperoxide. Human mesenchymal stem cells (hMSCs) exhibit limited proliferative potential in vitro, the so-called Hayflick limit. According to the free-radical theory, reactive oxygen species (ROS) might be the candidates responsible for senescence and age-related diseases. H(2)O(2) may be responsible for the production of high levels of ROS, in which the redox balance is disturbed and the cells shift into a state of oxidative stress, which subsequently leads to premature senescence with shortening telomeres. H(2)O(2) has been the most commonly used inducer of SIPS, which shares features of replicative senescence (RS) including a similar morphology, senescence-associated β-galactosidase activity, cell cycle regulation, etc. Therefore, in this study, the senescence of hMSC during SIPS was confirmed using a range of different analytical methods. In addition, we determined five differentially expressed spots in the 2-DE map, which were identified as Annexin A2 (ANXA2), myosin light chain 2 (MLC2), peroxisomal enoyl-CoA hydratase 1 (ECH1), prosomal protein P30-33K (PSMA1) and mutant β-actin by ESI-Q-TOF MS/MS. Also, proton ((1)H) nuclear magnetic resonance spectroscopy (NMR) was used to elucidate the difference between metabolites in the control and hMSCs treated with H(2)O(2). Among these metabolites, choline and leucine were identified by (1)H-NMR as up-regulated metabolites and glycine and proline were identified as down-regulated metabolites. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. A role for mitochondrial oxidants in stress-induced premature senescence of human vascular smooth muscle cells

    Directory of Open Access Journals (Sweden)

    Yogita Mistry

    2013-01-01

    Full Text Available Mitochondria are a major source of cellular oxidants and have been implicated in aging and associated pathologies, notably cardiovascular diseases. Vascular cell senescence is observed in experimental and human cardiovascular pathologies. Our previous data highlighted a role for angiotensin II in the induction of telomere-dependent and -independent premature senescence of human vascular smooth muscle cells and suggested this was due to production of superoxide by NADPH oxidase. However, since a role for mitochondrial oxidants was not ruled out we hypothesise that angiotensin II mediates senescence by mitochondrial superoxide generation and suggest that inhibition of superoxide may prevent vascular smooth muscle cell aging in vitro. Cellular senescence was induced using a stress-induced premature senescence protocol consisting of three successive once-daily exposure of cells to 1×10−8 mol/L angiotensin II and was dependent upon the type-1 angiotensin II receptor. Angiotensin stimulated NADPH-dependent superoxide production as estimated using lucigenin chemiluminescence in cell lysates and this was attenuated by the mitochondrial electron transport chain inhibitor, rotenone. Angiotensin also resulted in an increase in mitoSOX fluorescence indicating stimulation of mitochondrial superoxide. Significantly, the induction of senescence by angiotensin II was abrogated by rotenone and by the mitochondria-targeted superoxide dismutase mimetic, mitoTEMPO. These data suggest that mitochondrial superoxide is necessary for the induction of stress-induced premature senescence by angiotensin II and taken together with other data suggest that mitochondrial cross-talk with NADPH oxidases, via as yet unidentified signalling pathways, is likely to play a key role.

  16. Transcriptional up-regulation of antioxidant genes by PPARδ inhibits angiotensin II-induced premature senescence in vascular smooth muscle cells

    International Nuclear Information System (INIS)

    Kim, Hyo Jung; Ham, Sun Ah; Paek, Kyung Shin; Hwang, Jung Seok; Jung, Si Young; Kim, Min Young; Jin, Hanna; Kang, Eun Sil; Woo, Im Sun; Kim, Hye Jung; Lee, Jae Heun; Chang, Ki Churl; Han, Chang Woo; Seo, Han Geuk

    2011-01-01

    Research highlights: → Activation of PPARδ by GW501516 significantly inhibited Ang II-induced premature senescence in hVSMCs. → Agonist-activated PPARδ suppressed generation of Ang II-triggered ROS with a concomitant reduction in DNA damage. → GW501516 up-regulated expression of antioxidant genes, such as GPx1, Trx1, Mn-SOD and HO-1. → Knock-down of these antioxidant genes abolished the effects of GW501516 on ROS production and premature senescence. -- Abstract: This study evaluated peroxisome proliferator-activated receptor (PPAR) δ as a potential target for therapeutic intervention in Ang II-induced senescence in human vascular smooth muscle cells (hVSMCs). Activation of PPARδ by GW501516, a specific agonist of PPARδ, significantly inhibited the Ang II-induced premature senescence of hVSMCs. Agonist-activated PPARδ suppressed the generation of Ang II-triggered reactive oxygen species (ROS) with a concomitant reduction in DNA damage. Notably, GW501516 up-regulated the expression of antioxidant genes, such as glutathione peroxidase 1, thioredoxin 1, manganese superoxide dismutase and heme oxygenase 1. siRNA-mediated down-regulation of these antioxidant genes almost completely abolished the effects of GW501516 on ROS production and premature senescence in hVSMCs treated with Ang II. Taken together, the enhanced transcription of antioxidant genes is responsible for the PPARδ-mediated inhibition of premature senescence through sequestration of ROS in hVSMCs treated with Ang II.

  17. Hypervitaminosis A-induced premature closure of epiphyses (physeal obliteration) in humans and calves (hyena disease): a historical review of the human and veterinary literature

    International Nuclear Information System (INIS)

    Rothenberg, Alexis B.; Berdon, Walter E.; Woodard, J.C.; Cowles, Robert A.

    2007-01-01

    Vitamin A toxicity in the infant, which now occurs rarely from dietary overdosage, was recognized in the 1940s as painful periostitis with rare progression to premature closure of the lower limb epiphyses. Decades later, most cases of vitamin A-induced premature epiphyseal closure (physeal obliteration) occur in pediatric dermatologic patients given vitamin A analogues. This phenomenon resembles a strange disease discovered in more recent years in calves with closed epiphyses of the hind limbs, known as hyena disease. This was a mystery until proved to be caused by vitamin A toxicity from enriched grain that causes the calves to have short hind limbs that resemble those of a hyena and gait disturbance. This historical review links the human and veterinary literature in terms of vitamin A-induced epiphyseal closure using a case report format of a 16-month-old human infant with closed knee epiphyses and gait disturbance that is reminiscent of hyena disease seen in calves. (orig.)

  18. Myopia in premature babies with and without retinopathy of prematurity.

    OpenAIRE

    Nissenkorn, I; Yassur, Y; Mashkowski, D; Sherf, I; Ben-Sira, I

    1983-01-01

    One hundred and fifty-five premature infants weighing 600-2000 g were followed up during 1974-80 for the presence of retinopathy of prematurity (ROP) and for the existence of myopia. 50% of the premature infants who had ROP were myopic, while only 16% myopic premature infants were found among those who did not have ROP. There was a positive correlation between the degree of myopia and the severity of cicatricial ROP. No difference existed in the frequency and degree of myopia between prematur...

  19. Retinopathy of prematurity and neurodevelopmental disabilities in premature infants.

    Science.gov (United States)

    Beligere, Nagamani; Perumalswamy, Vijayalaksmi; Tandon, Manish; Mittal, Amit; Floora, Jayasheele; Vijayakumar, B; Miller, Marilyn T

    2015-10-01

    Prematurity is a major global health issue leading to high mortality and morbidity among the survivors. Neurodevelopmental disability (NDD) and retinopathy of prematurity (ROP) are the most common complications of prematurity. In fact, ROP is the second leading cause of childhood blindness in the world. Although there is much information regarding the occurrence of ROP and of NDD in premature infants, there have been few studies on ROP and its association with NDD. The objectives of this article are to review the current literature on the subject and to publish our own findings concerning the association between ROP and NDD in premature infants. The review suggests that although NDDs are related to degree of prematurity, NDD could also be the result of visual impairments resulting from ROP. Our own study shows a close association between NDD and zonal involvement of ROP: higher NDD if zone 1 is involved and less if zone 3 is involved. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Feelings experienced by parents when their premature children are hospitalized. A contribution to the humanized care

    Directory of Open Access Journals (Sweden)

    Maria Fernanda Acosta Romo

    2017-05-01

    Full Text Available Objective: To understand the meaning of the experiences felt by parents of premature children who are hospitalized in the Neonatal Intensive Care Unit of a hospital in the city of Pasto, Nariño, taking into account the phenomenological theory of Edmund Husserl. Materials and methods: In order to understand these experiences, a qualitative phenomenological study was carried out with eight parents in a range of age between 17 and 35. Results: The investigative process identified five categories, which emerged from the process of codification or nomothetic analysis of the speeches convergences. Two of these categories were considered for this article: Feelings and affective bond as an expression of parental love and process of interaction with the health staff. Conclusion: The parents of children in hospital were not prepared for the birth of a premature baby, so they experienced feelings of sadness, anxiety, self-criticism and fear, altering the affective bond between parents and children.

  1. Feeding premature neonates: Kinship and species in translational neonatology.

    Science.gov (United States)

    Dam, Mie S; Juhl, Sandra M; Sangild, Per T; Svendsen, Mette N

    2017-04-01

    Kinship, understood as biogenetic proximity, between a chosen animal model and a human patient counterpart, is considered essential to the process of 'translating' research from the experimental animal laboratory to the human clinic. In the Danish research centre, NEOMUNE, premature piglets are fed a novel milk diet (bovine colostrum) to model the effects of this new diet in premature infants. Our ethnographic fieldwork in an experimental pig laboratory and a neonatal intensive care unit (NICU) in 2013-2014 shows that regardless of biogenetics, daily practices of feeding, housing, and clinical care hold the potential for stimulating and eroding kinship relations between human and nonhuman actors. In the laboratory, piglets and researchers form 'interspecies-milk-kinships' that entail the intimate care crucial to keeping the compromised piglets alive during the experiments, thereby enhancing what the researchers refer to as the 'translatability' of the results. In the NICU, parents of premature infants likewise imagine a kind of interspecies kinship when presented with the option to supplement mother's own milk with bovine colostrum for the first weeks after birth. However, in this setting the NICU parents may perceive the animality of bovine colostrum, and the background information obtained in piglets, as a threat to the infants' connection to their biological parents as well as the larger human collective. Our study argues that the 'species flexibility' of premature beings profoundly shapes the translational processes in the field of neonatology research. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Introduction of a normal human chromosome 8 corrects abnormal phenotypes of Werner syndrome cells immortalized by expressing an hTERT gene

    International Nuclear Information System (INIS)

    Ariyoshi, Kentaro; Kodama, Seiji; Suzuki, Keiji; Goto, Makoto; Oshimura, Mitsuo; Ishizaki, Kanji; Watanabe, Masami

    2009-01-01

    Werner syndrome (WS) is an autosomal recessive disease characterized by premature aging and caused by mutations of the WRN gene mapped at 8p12. To examine functional complementation of WS phenotypes, we introduced a normal human chromosome 8 into a strain of WS fibroblasts (WS3RGB) immortalized by expressing a human telomerase reverse transcriptase subunit (hTERT) gene. Here, we demonstrate that the abnormal WS phenotypes including cellular sensitivities to 4-nitroquinoline-1-oxide (4NQO) and hydroxy urea (HU), and chromosomal radiosensitivity at G 2 phase are corrected by expression of the WRN gene mediated by introducing a chromosome 8. This indicates that those multiple abnormal WS phenotypes are derived from a primary, but not secondary, defect in the WRN gene. (author)

  3. Endometrial Receptivity Profile in Patients with Premature Progesterone Elevation on the Day of hCG Administration

    Directory of Open Access Journals (Sweden)

    Delphine Haouzi

    2014-01-01

    Full Text Available The impact of a premature elevation of serum progesterone level, the day of hCG administration in patients under controlled ovarian stimulation during IVF procedure, on human endometrial receptivity is still debated. In the present study, we investigated the endometrial gene expression profile shifts during the prereceptive and receptive secretory stage in patients with normal and elevated serum progesterone level on the day of hCG administration in fifteen patients under stimulated cycles. Then, specific biomarkers of endometrial receptivity in these two groups of patients were tested. Endometrial biopsies were performed on oocyte retrieval day and on day 3 of embryo transfer, respectively, for each patient. Samples were analysed using DNA microarrays and qRT-PCR. The endometrial gene expression shift from the prereceptive to the receptive stage was altered in patients with high serum progesterone level (>1.5 ng/mL on hCG day, suggesting accelerated endometrial maturation during the periovulation period. This was confirmed by the functional annotation of the differentially expressed genes as it showed downregulation of cell cycle-related genes. Conversely, the profile of endometrial receptivity was comparable in both groups. Premature progesterone rise alters the endometrial gene expression shift between the prereceptive and the receptive stage but does not affect endometrial receptivity.

  4. [Estimation on the indirect economic burden of disease-related premature deaths in China, 2012].

    Science.gov (United States)

    Yang, Juan; Feng, Luzhao; Zheng, Yaming; Yu, Hongjie

    2014-11-01

    To estimate the indirect economic burden of disease-related premature deaths in China, 2012. Both human capital approach and friction cost methods were used to compute the indirect economic burden of premature deaths from the following sources: mortality from the national disease surveillance system in 2012, average annual income per capita from the China Statistic Yearbook in 2012, population size from the 2010 China census, and life expectancy in China from the World Health Organization life table. Data from the Human Capital Approach Estimates showed that the indirect economic burden of premature deaths in China was 425.1 billion in 2012, accounting for 8‰ of the GDP. The indirect economic burden of chronic non-communicable diseases associated premature deaths was accounted for the highest proportion(67.1%, 295.4 billion), followed by those of injuries related premature deaths (25.6% , 108.9 billion), infectious diseases, maternal and infants diseases, and malnutrition related deaths (6.4% , 26.9 billion). The top five premature deaths that cause the indirect economic burden were malignancy, cardiovascular diseases, unintentional injuries, intentional injuries, and diseases of the respiratory system. The indirect economic burden of premature deaths mainly occurred in the population of 20-59 year-olds. Under the Friction Cost method, the estimates appeared to be 0.11%-3.49% of the total human capital approach estimates. Premature death caused heavy indirect economic burden in China. Chronic non-communicable diseases and injuries seemed to incur the major disease burden. The indirect economic burden of premature deaths mainly occurred in the working age group.

  5. Your Premature Baby

    Science.gov (United States)

    ... volunteer leader Partner Spotlight Become a partner World Prematurity Day What's happening in your area Find out ... 3 weeks after a premature birth. Retinopathy of prematurity (ROP) . This is an abnormal growth of blood ...

  6. Premature Senescence Induced by Ionizing Radiation Requires AKT Activity and Reactive Oxygen Species in Glioma

    International Nuclear Information System (INIS)

    Lee, Je Jung; Kim, Bong Cho; Yoo, Hee Jung; Lee, Jae Seon

    2010-01-01

    Loss of PTEN, a tumor suppressor gene has frequently observed in human gliomas, which conferred AKT activation and resistance to ionizing radiation (IR) and anti-cancer drugs. Recent reports have shown that AKT activation induces premature senescence through increase of oxygen consumption and inhibition of expression of ROS scavenging enzymes. In this study, we compared cellular response to IR in the PTEN-deficient U87, U251, U373 or PTEN-proficient LN18, LN428 glioma cells

  7. Hypoxia-induced retinal neovascularization in zebrafish embryos: a potential model of retinopathy of prematurity.

    Science.gov (United States)

    Wu, Yu-Ching; Chang, Chao-Yuan; Kao, Alex; Hsi, Brian; Lee, Shwu-Huey; Chen, Yau-Hung; Wang, I-Jong

    2015-01-01

    Retinopathy of prematurity, formerly known as a retrolental fibroplasia, is a leading cause of infantile blindness worldwide. Retinopathy of prematurity is caused by the failure of central retinal vessels to reach the retinal periphery, creating a nonperfused peripheral retina, resulting in retinal hypoxia, neovascularization, vitreous hemorrhage, vitreoretinal fibrosis, and loss of vision. We established a potential retinopathy of prematurity model by using a green fluorescent vascular endothelium zebrafish transgenic line treated with cobalt chloride (a hypoxia-inducing agent), followed by GS4012 (a vascular endothelial growth factor inducer) at 24 hours postfertilization, and observed that the number of vascular branches and sprouts significantly increased in the central retinal vascular trunks 2-4 days after treatment. We created an angiography method by using tetramethylrhodamine dextran, which exhibited severe vascular leakage through the vessel wall into the surrounding retinal tissues. The quantification of mRNA extracted from the heads of the larvae by using real-time quantitative polymerase chain reaction revealed a twofold increase in vegfaa and vegfr2 expression compared with the control group, indicating increased vascular endothelial growth factor signaling in the hypoxic condition. In addition, we demonstrated that the hypoxic insult could be effectively rescued by several antivascular endothelial growth factor agents such as SU5416, bevacizumab, and ranibizumab. In conclusion, we provide a simple, highly reproducible, and clinically relevant retinopathy of prematurity model based on zebrafish embryos; this model may serve as a useful platform for clarifying the mechanisms of human retinopathy of prematurity and its progression.

  8. Associations Between Nurse-Guided Variables and Plasma Oxytocin Trajectories in Premature Infants During Initial Hospitalization.

    Science.gov (United States)

    Weber, Ashley; Harrison, Tondi M; Sinnott, Loraine; Shoben, Abigail; Steward, Deborah

    2018-02-01

    Oxytocin (OT) is a social hormone that may help researchers understand how nurse-guided interventions during initial infant hospitalization, such as supporting human milk expression, promoting comforting touch, and reducing exposure to stressors, affect preterm brain development. To determine whether factors related to human milk, touch, or stressor exposure are related to plasma OT trajectories in premature infants. Plasma from 33 premature infants, born gestational ages 25 to (Equation is included in full-text article.)weeks, was collected at 14 days of life and then weekly until 34 weeks' corrected gestational age (CGA). Variables related to feeding volumes of human milk and formula; touch, as indexed by skin-to-skin contact (SSC) and swaddled holding; and clinical stressors were extracted from the electronic medical record. Linear mixed-models tested associations between nurse-guided variables and plasma OT trajectories. In the final model, same-day SSC was positively related not only to plasma OT levels at 27 weeks' CGA (β= .938, P = .002) but also to a decline in plasma OT levels over time (β=-.177, P = .001). Volume of enteral feeds (mL/kg/d), its interaction with CGA, and number of stressful procedures were not statistically significant (β= .011, P = .077; β=-.002, P = .066; and β= .007, P = .062, respectively). Nurse-guided interventions are associated with infant plasma OT levels, suggesting nurses may impact the neurobiology of the developing premature infant. Replication with larger sample sizes and randomized controlled trial designs is needed to test effects of specific nursing interventions on infant OT.

  9. Study on biological dosimetry of premature chromosome condensation technique

    International Nuclear Information System (INIS)

    Jiang Bo

    2005-01-01

    The premature chromosome condensation technique has been applied for biological dosimetry purpose. Premature chromo-some condensation was induced by incubating unstimulated human peripheral blood lymphocytes in the presence of okadaic acid or calyculin A (a phosphatase inhibitor) which eliminated the need for fusion with mitotic cells. It is now possible to examine the early damage induced by radiation. It is simple, exact when it combines with fluorecence in situ hybridization. (authors)

  10. Recapitulation of premature ageing with iPSCs from Hutchinson-Gilford progeria syndrome.

    Science.gov (United States)

    Liu, Guang-Hui; Barkho, Basam Z; Ruiz, Sergio; Diep, Dinh; Qu, Jing; Yang, Sheng-Lian; Panopoulos, Athanasia D; Suzuki, Keiichiro; Kurian, Leo; Walsh, Christopher; Thompson, James; Boue, Stephanie; Fung, Ho Lim; Sancho-Martinez, Ignacio; Zhang, Kun; Yates, John; Izpisua Belmonte, Juan Carlos

    2011-04-14

    Hutchinson-Gilford progeria syndrome (HGPS) is a rare and fatal human premature ageing disease, characterized by premature arteriosclerosis and degeneration of vascular smooth muscle cells (SMCs). HGPS is caused by a single point mutation in the lamin A (LMNA) gene, resulting in the generation of progerin, a truncated splicing mutant of lamin A. Accumulation of progerin leads to various ageing-associated nuclear defects including disorganization of nuclear lamina and loss of heterochromatin. Here we report the generation of induced pluripotent stem cells (iPSCs) from fibroblasts obtained from patients with HGPS. HGPS-iPSCs show absence of progerin, and more importantly, lack the nuclear envelope and epigenetic alterations normally associated with premature ageing. Upon differentiation of HGPS-iPSCs, progerin and its ageing-associated phenotypic consequences are restored. Specifically, directed differentiation of HGPS-iPSCs to SMCs leads to the appearance of premature senescence phenotypes associated with vascular ageing. Additionally, our studies identify DNA-dependent protein kinase catalytic subunit (DNAPKcs, also known as PRKDC) as a downstream target of progerin. The absence of nuclear DNAPK holoenzyme correlates with premature as well as physiological ageing. Because progerin also accumulates during physiological ageing, our results provide an in vitro iPSC-based model to study the pathogenesis of human premature and physiological vascular ageing.

  11. Retinopathy of Prematurity

    Science.gov (United States)

    Steinweg, Sue Byrd; Griffin, Harold C.; Griffin, Linda W.; Gingras, Happy

    2005-01-01

    The eyes of premature infants are especially vulnerable to injury after birth. A serious complication is called retinopathy of prematurity (ROP), which is abnormal growth of the blood vessels in an infant's eye. Retinopathy of prematurity develops when abnormal blood vessels grow and spread throughout the retina, which is the nerve tissue at the…

  12. Production of a Marfan cellular phenotype by expressing a mutant human fibrillin allele on a normal human or murine genetic background

    Energy Technology Data Exchange (ETDEWEB)

    Eldadah, Z.A.; Dietz, H.C. [Johns Hopkins Univ. School of Medicine, Baltimore, MD (United States); Brenn, T. [Stanford Univ. Medical Center, CA (United States)] [and others

    1994-09-01

    The Marfan Syndrome (MFS) is a heritable disorder of connective tissue caused by defects in fibrillin (FBN1), a 350 kD glycoprotein and principal component of the extracellular microfibril. Previous correlations of mutant transcript level and disease severity suggested a dominant negative model of MFS pathogenesis. To address this hypothesis we assembled an expression construct containing the mutant allele from a patient with severe MFS. This mutation causes skipping of FBN1 exon 2 and a frame shift, leading to a premature termination codon in exon 4. The predicted peptide would thus consist of 55 wild type and 45 missense amino acids. The construct was stably transfected into cultured human and mouse fibroblasts, and several clonal cell populations were established. Human and mouse cells expressing the truncated peptide exhibited markedly diminished fibrillin deposition and disorganized microfibrillar architecture by immunofluorescence. Pulse-chase analysis of these cells demonstrated normal levels of fibrillin synthesis but substantially decreased fibrillin deposition into the extracellular matrix. These data illustrate that expression of a mutant FBN1 allele, on a background of two normal alleles, is sufficient to disrupt normal fibrillin aggregation and reproduce the MFS cellular phenotype. This provides confirmation of a dominant negative model of MFS pathogenesis and may offer mutant allele knockout as a strategy for gene therapy. In addition, these data underscore the importance of the FBN1 amino-terminus in normal multimer formation and suggest that expression of the human extreme 5{prime} FBN1 coding sequence may be sufficient, in isolation, to produce an animal model of MFS. Indeed, transgenic mice harboring this mutant allele have been produced, and phenotype analysis is currently in progress.

  13. Expression and function of Delta-like ligand 4 in a rat model of retinopathy of prematurity

    Institute of Scientific and Technical Information of China (English)

    Shaoyang Shi; Xun Li; You Li; Cunwen Pei; Hongwei Yang; Xiaolong Chen

    2013-01-01

    The Delta-like ligand 4/Notch signaling pathway was shown to participate in the process of retinal development and angiogenesis. However, the function of the Delta-like ligand 4/Notch signaling pathway in retinopathy of prematurity requires further study. Retinopathy of prematurity was induced in 5-day-old Sprague-Dawley rats exposed to hyperoxia for 7 days, and then returned to room air. Reverse transcription-PCR and western blot revealed that Delta-like ligand 4 levels decreased at postnatal day 12 and increased at postnatal day 17 in retinopathy of prematurity rats. Flat-mounted adenosine diphosphatase stained retina and hematoxylin-eosin stained retinal tissue slices showed that the clock hour scores and the nuclei counts in retinopathy of prematurity rats were significantly different compared to normal control rats. After retinopathy of prematurity rats were intravitreally injected with Delta-like ligand 4 monoclonal antibody to inhibit the Delta-like ligand 4/Notch signaling pathway, there was a significant increase in the severity of retinal neovascularization (clock hours) in the intravitreally injected eyes. The nuclei count was highly correlated with the clock hour score. These results suggest that Delta-like ligand 4/Notch signaling plays an essential role in the process of physiological and pathological angiogenesis in the retina.

  14. Early or Premature Menopause

    Science.gov (United States)

    ... email updates Enter email Submit Early or premature menopause Menopause that happens before age 40 is called ... What is the difference between early and premature menopause? Early or premature menopause happens when ovaries stop ...

  15. The human neonatal small intestine has the potential for arginine synthesis; developmental changes in the expression of arginine-synthesizing and -catabolizing enzymes

    Directory of Open Access Journals (Sweden)

    Ruijter Jan M

    2008-11-01

    Full Text Available Abstract Background Milk contains too little arginine for normal growth, but its precursors proline and glutamine are abundant; the small intestine of rodents and piglets produces arginine from proline during the suckling period; and parenterally fed premature human neonates frequently suffer from hypoargininemia. These findings raise the question whether the neonatal human small intestine also expresses the enzymes that enable the synthesis of arginine from proline and/or glutamine. Carbamoylphosphate synthetase (CPS, ornithine aminotransferase (OAT, argininosuccinate synthetase (ASS, arginase-1 (ARG1, arginase-2 (ARG2, and nitric-oxide synthase (NOS were visualized by semiquantitative immunohistochemistry in 89 small-intestinal specimens. Results Between 23 weeks of gestation and 3 years after birth, CPS- and ASS-protein content in enterocytes was high and then declined to reach adult levels at 5 years. OAT levels declined more gradually, whereas ARG-1 was not expressed. ARG-2 expression increased neonatally to adult levels. Neurons in the enteric plexus strongly expressed ASS, OAT, NOS1 and ARG2, while varicose nerve fibers in the circular layer of the muscularis propria stained for ASS and NOS1 only. The endothelium of small arterioles expressed ASS and NOS3, while their smooth-muscle layer expressed OAT and ARG2. Conclusion The human small intestine acquires the potential to produce arginine well before fetuses become viable outside the uterus. The perinatal human intestine therefore resembles that of rodents and pigs. Enteral ASS behaves as a typical suckling enzyme because its expression all but disappears in the putative weaning period of human infants.

  16. Outcomes for Extremely Premature Infants

    Science.gov (United States)

    Glass, Hannah C.; Costarino, Andrew T.; Stayer, Stephen A.; Brett, Claire; Cladis, Franklyn; Davis, Peter J.

    2015-01-01

    Premature birth is a significant cause of infant and child morbidity and mortality. In the United States, the premature birth rate, which had steadily increased during the 1990s and early 2000s, has decreased annually for four years and is now approximately 11.5%. Human viability, defined as gestational age at which the chance of survival is 50%, is currently approximately 23–24 weeks in developed countries. Infant girls, on average, have better outcomes than infant boys. A relatively uncomplicated course in the intensive care nursery for an extremely premature infant results in a discharge date close to the prenatal EDC. Despite technological advances and efforts of child health experts during the last generation, the extremely premature infant (less than 28 weeks gestation) and extremely low birth weight infant (ELBW) (CPAP, mechanical ventilation, and exogenous surfactant increased survival and spurred the development of neonatal intensive care in the 1970s through the early 1990s. Routine administration of antenatal steroids during premature labor improved neonatal mortality and morbidity in the late 1990s. The recognition that chronic postnatal administration of steroids to infants should be avoided may have improved outcomes in the early 2000s. Evidence from recent trials attempting to define the appropriate target for oxygen saturation in preterm infants suggests arterial oxygen saturation between 91–95% (compared to 85–89%) avoids excess mortality. However, final analyses of data from these trials have not been published, so definitive recommendations are still pending The development of neonatal neurocognitive care visits may improve neurocognitive outcomes in this high-risk group. Long-term follow up to detect and address developmental, learning, behavioral, and social problems is critical for children born at these early gestational ages. The striking similarities in response to extreme prematurity in the lung and brain imply that agents and

  17. Hepatic Insulin Resistance and Altered Gluconeogenic Pathway in Premature Baboons.

    Science.gov (United States)

    McGill-Vargas, Lisa; Gastaldelli, Amalia; Liang, Hanyu; Anzueto Guerra, Diana; Johnson-Pais, Teresa; Seidner, Steven; McCurnin, Donald; Muscogiuri, Giovanna; DeFronzo, Ralph; Musi, Nicolas; Blanco, Cynthia

    2017-05-01

    Premature infants have altered glucose regulation early in life and increased risk for diabetes in adulthood. Although prematurity leads to an increased risk of diabetes and metabolic syndrome in adult life, the role of hepatic glucose regulation and adaptation to an early extrauterine environment in preterm infants remain unknown. The purpose of this study was to investigate developmental differences in glucose metabolism, hepatic protein content, and gene expression of key insulin-signaling/gluconeogenic molecules. Fetal baboons were delivered at 67%, 75%, and term gestational age and euthanized at birth. Neonatal baboons were delivered prematurely (67% gestation), survived for two weeks, and compared with similar postnatal term animals and underwent serial hyperinsulinemic-euglycemic clamp studies. Premature baboons had decreased endogenous glucose production (EGP) compared with term animals. Consistent with these results, the gluconeogenic molecule, phosphoenolpyruvate carboxykinase messenger RNA, was decreased in preterm baboons compared with terms. Hepatic insulin signaling was altered by preterm birth as evidenced by decreased insulin receptor-β, p85 subunit of phosphoinositide 3-kinase, phosphorylated insulin receptor substrate 1, and Akt-1 under insulin-stimulated conditions. Furthermore, preterm baboons failed to have the normal increase in glycogen synthase kinase-α from fetal to postnatal life. The blunted responses in hepatic insulin signaling may contribute to the hyperglycemia of prematurity, while impaired EGP leads to hypoglycemia of prematurity. Copyright © 2017 Endocrine Society.

  18. Identification of 30 protein species involved in replicative senescence and stress-induced premature senescence

    DEFF Research Database (Denmark)

    Dierick, Jean François; Kalume, Dário E; Wenders, Frédéric

    2002-01-01

    Exposure of human proliferative cells to subcytotoxic stress triggers stress-induced premature senescence (SIPS) which is characterized by many biomarkers of replicative senescence. Proteomic comparison of replicative senescence and stress-induced premature senescence indicates that, at the level...

  19. Efficiency of antibiotic treatment of premature ejaculation in patients with type III prostatic inflammation

    Directory of Open Access Journals (Sweden)

    Teoman Cem Kadioglu

    2011-03-01

    Full Text Available The most common male sexual disorder is premature ejaculation as it affects 30-40% of sexually active men. Various studies showed that the correlation of prostatic inflammation and chronic bacterial prostatitis with premature ejaculation is present in more than half of the sufferers. These studies also show that more than 85% of prostatic inflammation cases was shown to be caused by chronic prostatitis in the premature ejaculation patient group. Even though this relation is evident, the effect of antibiotic treatment of premature ejaculation in patients with chronic prostatitis has only recently being investigated extensively. In this study, 36 men suffering from secondary premature ejaculation who were included the study. These patients had no erectile dysfunction problems and were included in the study after they timed intravaginal ejaculatory latency in their last 3 intercourses to see that time was less than 2 minutes in each trial. To evaluate the prostatic inflammation, diagnosis was made by identifying 10 or more white blood cells per high power field in expressed prostatic secretions. 22 of 36 premature ejaculation patients in our study had more than 10 white blood cells in thier expressed prostatic secretions and were diagnosed to have prostatic inflammation. The other 14 patients were included in the study as the control group. Following one month antibiotic treatment 78% patients in the study group returned with the information that all 3 of their last intercourses ended with more than 2 minutes of intravaginal ejaculatory latency time while none of the control group reported similarly. No side effects were reported by any of the patients due to antibiotic usage. Our study shows that patients with PE that may benefit from month-long quinolone antibiotic therapy can be screened for by checking their expressed prostatic secretions under a microscope in the office. A more accurate definition of premature ejaculation, a scale for

  20. Pharmacotherapy for premature ejaculation

    NARCIS (Netherlands)

    Waldinger, Marcel D

    2014-01-01

    PURPOSE OF REVIEW: As there are various drugs and different treatment strategies to delay ejaculation, a review of the current drug treatments for premature ejaculation is relevant for daily clinical practice. RECENT FINDINGS: There are four premature ejaculation subtypes: lifelong premature

  1. Familial aggregation of phenotypic expression of premature hair hypopigmentation in the craniofacial region

    Directory of Open Access Journals (Sweden)

    Corey Black

    2015-04-01

    Full Text Available There are many patients who experience premature hypopigmentation of hair, but do not understand the underlying causes and potential dangers associated with them. The causes range from genetic predisposition to environmental influences such as tobacco use. Premature hypopigmentation of the hair shaft can also be associated with many syndromes; some which cause dental anomalies. Today, treatment options are limited for patients, although various studies are being done on mice to target the underlying mechanism of action. Understanding the differences between all of the possible causes of this particular phenotype can help clinicians better identify the symptoms, educate patients, and possibly modify treatment to suit the needs of each patient on an individual basis.

  2. Randomized trial of exclusive human milk versus preterm formula diets in extremely premature infants.

    Science.gov (United States)

    Cristofalo, Elizabeth A; Schanler, Richard J; Blanco, Cynthia L; Sullivan, Sandra; Trawoeger, Rudolf; Kiechl-Kohlendorfer, Ursula; Dudell, Golde; Rechtman, David J; Lee, Martin L; Lucas, Alan; Abrams, Steven

    2013-12-01

    To compare the duration of parenteral nutrition, growth, and morbidity in extremely premature infants fed exclusive diets of either bovine milk-based preterm formula (BOV) or donor human milk and human milk-based human milk fortifier (HUM), in a randomized trial of formula vs human milk. Multicenter randomized controlled trial. The authors studied extremely preterm infants whose mothers did not provide their milk. Infants were fed either BOV or an exclusive human milk diet of pasteurized donor human milk and HUM. The major outcome was duration of parenteral nutrition. Secondary outcomes were growth, respiratory support, and necrotizing enterocolitis (NEC). Birth weight (983 vs 996 g) and gestational age (27.5 vs 27.7 wk), in BOV and HUM, respectively, were similar. There was a significant difference in median parenteral nutrition days: 36 vs 27, in BOV vs HUM, respectively (P = .04). The incidence of NEC in BOV was 21% (5 cases) vs 3% in HUM (1 case), P = .08; surgical NEC was significantly higher in BOV (4 cases) than HUM (0 cases), P = .04. In extremely preterm infants given exclusive diets of preterm formula vs human milk, there was a significantly greater duration of parenteral nutrition and higher rate of surgical NEC in infants receiving preterm formula. This trial supports the use of an exclusive human milk diet to nourish extremely preterm infants in the neonatal intensive care unit. Copyright © 2013 Mosby, Inc. All rights reserved.

  3. The Mediterranean diet adherence by pregnant women delivering prematurely: association with size at birth and complications of prematurity.

    Science.gov (United States)

    Parlapani, Elisavet; Agakidis, Charalampos; Karagiozoglou-Lampoudi, Thomais; Sarafidis, Kosmas; Agakidou, Eleni; Athanasiadis, Apostolos; Diamanti, Elisavet

    2017-11-13

    The Mediterranean diet (MD) is associated with decreased risk of metabolic syndrome and gestational diabetes due to the anti-inflammatory and antioxidative properties of its components. The aim was to investigate the potential association of MD adherence (MDA) during pregnancy by mothers delivering prematurely, with intrauterine growth as expressed by neonates' anthropometry at birth and complications of prematurity. This is a single-center, prospective, observational cohort study of 82 women who delivered preterm singletons at post conceptional age (PCA) ≤ 34 weeks and their live-born neonates. Maternal and neonatal demographic and clinical data were recorded. All mothers filled in a food frequency questionnaire, and the MDA score was calculated. Based on 50th centile of MD score, participants were classified into high-MDA and low-MDA groups. The low-MDA mothers had significantly higher pregestational BMI and rates of overweight/obesity (odd ratios (OR) 3.5) and gestational hypertension/preeclampsia (OR 3.8). Neonates in the low-MDA group had significantly higher incidence of intrauterine growth restriction (IUGR) (OR 3.3) and lower z-scores of birth weight and BMI. Regarding prematurity-related complications, the low MDA-group was more likely to develop necrotizing enterocolitis, bronchopulmonary dysplasia, and retinopathy of prematurity (OR 3.2, 1.3, and 1.6, respectively), while they were less likely to develop respiratory distress syndrome (OR 0.49), although the differences were not statistically significant. However, adjustment for confounders revealed MDA as a significant independent predictor of hypertension/preeclampsia, IUGR, birth weight z-score, necrotizing enterocolitis, and bronchopulmonary dysplasia. High MDA during pregnancy may favorably affect intrauterine growth and certain acute and chronic complications of prematurity as well as maternal hypertension/preeclampsia.

  4. [Laser treatment for retinopathy of prematurity in neonatal intensive care units. Premature Eye Rescue Program].

    Science.gov (United States)

    Maka, Erika; Imre, László; Somogyvári, Zsolt; Németh, János

    2015-02-01

    Retinopathy of prematurity is a leading cause of childhood blindness around the world. The Department of Ophthalmology at the Semmelweis University and the Peter Cerny Neonatal Emergency and Ambulance Service started an innovative Premature Eye Rescue Program to reduce the non-essential transport of premature babies suffering from retinopathy of prematurity. During the first 5 years 186 eyes of 93 premature babies were treated at the bedside with stage 3 retinopathy of prematurity in the primary hospitals. In this first 5-years period the authors reduced the number of transports of premature babies for laser treatment; 93 children avoided the unnecessary transport, saving altogether a distance of 21,930 kilometers for children, as well as the ambulance service. The Premature Eye Rescue Program offers a good and effective alternative for treatment of retinopathy in the primary hospitals. The authors propose the national extension of this program.

  5. Recombinant Human Acidic Fibroblast Growth Factor (aFGF) Expressed in Nicotiana benthamiana Potentially Inhibits Skin Photoaging.

    Science.gov (United States)

    Ha, Jang-Ho; Kim, Ha-Neul; Moon, Ki-Beom; Jeon, Jae-Heung; Jung, Dai-Hyun; Kim, Su-Jung; Mason, Hugh S; Shin, Seo-Yeon; Kim, Hyun-Soon; Park, Kyung-Mok

    2017-07-01

    Responding to the need for recombinant acidic fibroblast growth factor in the pharmaceutical and cosmetic industries, we established a scalable expression system for recombinant human aFGF using transient and a DNA replicon vector expression in Nicotiana benthamiana . Recombinant human-acidic fibroblast growth factor was recovered following Agrobacterium infiltration of N. benthamiana . The optimal time point at which to harvest recombinant human acidic fibroblast growth factor expressing leaves was found to be 4 days post-infiltration, before necrosis was evident. Commassie-stained SDS-PAGE gels of His-tag column eluates, concentrated using a 10 000 molecular weight cut-off column, showed an intense band at the expected molecular weight for recombinant human acidic fibroblast growth factor. An immunoblot confirmed that this band was recombinant human acidic fibroblast growth factor. Up to 10 µg recombinant human-acidic fibroblast growth factor/g of fresh leaves were achieved by a simple affinity purification protocol using protein extract from the leaves of agroinfiltrated N. benthamiana . The purified recombinant human acidic fibroblast growth factor improved the survival rate of UVB-irradiated HaCaT and CCD-986sk cells approximately 89 and 81 %, respectively. N. benthamiana -derived recombinant human acidic fibroblast growth factor showed similar effects on skin cell proliferation and UVB protection compared to those of Escherichia coli -derived recombinant human acidic fibroblast growth factor. Additionally, N. benthamiana- derived recombinant human acidic fibroblast growth factor increased type 1 procollagen synthesis up to 30 % as well as reduced UVB-induced intracellular reactive oxygen species generation in fibroblast (CCD-986sk) cells.UVB is a well-known factor that causes various types of skin damage and premature aging. Therefore, the present study demonstrated that N. benthamiana -derived recombinant human acidic fibroblast growth factor

  6. Apnea of prematurity

    Science.gov (United States)

    ... medlineplus.gov/ency/article/007227.htm Apnea of prematurity To use the sharing features on this page, ... down or stops from any cause. Apnea of prematurity refers to short episodes of stopped breathing in ...

  7. Effects of macelignan isolated from Myristica fragrans (nutmeg) on expression of matrix metalloproteinase-1 and type I procollagen in UVB-irradiated human skin fibroblasts

    International Nuclear Information System (INIS)

    Lee, Kyung-Eun; Mun, Sukyeong; Pyun, Hee-Bong; Kim, Myung-Suk; Hwang, Jae-Kwan

    2012-01-01

    Exposure to ultraviolet (UV) light causes premature skin aging that is associated with upregulated matrix metalloproteinases (MMPs) and decreased collagen synthesis. Macelignan, a natural lignan compound isolated from Myristica fragrans HOUTT. (nutmeg), has been reported to possess antioxidant and antiinflammatory activities. This study assessed the effects of macelignan on photoaging and investigated its mechanisms of action in UV-irradiated human skin fibroblasts (Hs68) by reverse transcription-polymerase chain reaction, Western blot analysis, 2', 7'-dichlorofluorescein diacetate assay, and enzyme-linked immunosorbent assay. Our results show that macelignan attenuated UV-induced MMP-1 expression by suppressing phosphorylation of mitogen-activated protein kinases (MAPKs) induced by reactive oxygen species. Macelignan also increased type I procollagen expression and secretion through transforming growth factor β (TGF-β)/Smad signaling. These findings indicate that macelignan regulates the expression of MMP-1 and type I procollagen in UV-irradiated human skin fibroblasts by modulating MAPK and TGF-β/Smad signaling, suggesting its potential as an efficacious antiphotoaging agent. (author)

  8. Expression of Pluripotency and Oocyte-Related Genes in Single Putative Stem Cells from Human Adult Ovarian Surface Epithelium Cultured In Vitro in the Presence of Follicular Fluid

    Directory of Open Access Journals (Sweden)

    Irma Virant-Klun

    2013-01-01

    Full Text Available The aim of this study was to trigger the expression of genes related to oocytes in putative ovarian stem cells scraped from the ovarian surface epithelium of women with premature ovarian failure and cultured in vitro in the presence of follicular fluid, rich in substances for oocyte growth and maturation. Ovarian surface epithelium was scraped and cell cultures were set up by scrapings in five women with nonfunctional ovaries and with no naturally present mature follicles or oocytes. In the presence of donated follicular fluid putative stem cells grew and developed into primitive oocyte-like cells. A detailed single-cell gene expression profiling was performed to elucidate their genetic status in comparison to human embryonic stem cells, oocytes, and somatic fibroblasts. The ovarian cell cultures depleted/converted reproductive hormones from the culture medium. Estradiol alone or together with other substances may be involved in development of these primitive oocyte-like cells. The majority of primitive oocyte-like cells was mononuclear and expressed several genes related to pluripotency and oocytes, including genes related to meiosis, although they did not express some important oocyte-specific genes. Our work reveals the presence of putative stem cells in the ovarian surface epithelium of women with premature ovarian failure.

  9. Shared molecular and cellular mechanisms of premature ageing and ageing-associated diseases.

    Science.gov (United States)

    Kubben, Nard; Misteli, Tom

    2017-10-01

    Ageing is the predominant risk factor for many common diseases. Human premature ageing diseases are powerful model systems to identify and characterize cellular mechanisms that underpin physiological ageing. Their study also leads to a better understanding of the causes, drivers and potential therapeutic strategies of common diseases associated with ageing, including neurological disorders, diabetes, cardiovascular diseases and cancer. Using the rare premature ageing disorder Hutchinson-Gilford progeria syndrome as a paradigm, we discuss here the shared mechanisms between premature ageing and ageing-associated diseases, including defects in genetic, epigenetic and metabolic pathways; mitochondrial and protein homeostasis; cell cycle; and stem cell-regenerative capacity.

  10. Cardiac output by Doppler echocardiography in the premature baboon: Comparison with radiolabeled microspheres

    International Nuclear Information System (INIS)

    Kinsella, J.P.; Morrow, W.R.; Gerstmann, D.R.; Taylor, A.F.; deLemos, R.A.

    1991-01-01

    Pulsed-Doppler echocardiography (PDE) is a useful noninvasive method for determining left ventricular output (LVO). However, despite increasingly widespread use in neonatal intensive care units, validation studies in prematures with cardiopulmonary disease are lacking. The purpose of this study was to compare radiolabeled microsphere (RLM) and PDE measurements of LVO, using the critically ill premature baboon as a model of the human neonate. Twenty-two paired RLM and PDE measurements of LVO were obtained in 14 animals between 3 and 24 h of age. Average PDE LVO was 152 ml/min/kg (range, 40-258 ml/min/kg) compared to 158 ml/min/kg (range, 67-278 ml/min/kg) measured by RLM. Linear regression analysis of the paired measurements showed good correlation with a slope near unity (gamma = 0.94x + 4.20, r = 0.91, SEE = 25.7 ml). The authors conclude that PDE determinations of LVO compare well with those measured by RLM in the premature baboon. PDE appears to provide a valid estimate of LVO and should be useful in human prematures with cardiopulmonary distress

  11. Expression of human cationic trypsinogen (PRSS1) in murine acinar cells promotes pancreatitis and apoptotic cell death

    Science.gov (United States)

    Athwal, T; Huang, W; Mukherjee, R; Latawiec, D; Chvanov, M; Clarke, R; Smith, K; Campbell, F; Merriman, C; Criddle, D; Sutton, R; Neoptolemos, J; Vlatković, N

    2014-01-01

    Hereditary pancreatitis (HP) is an autosomal dominant disease that displays the features of both acute and chronic pancreatitis. Mutations in human cationic trypsinogen (PRSS1) are associated with HP and have provided some insight into the pathogenesis of pancreatitis, but mechanisms responsible for the initiation of pancreatitis have not been elucidated and the role of apoptosis and necrosis has been much debated. However, it has been generally accepted that trypsinogen, prematurely activated within the pancreatic acinar cell, has a major role in the initiation process. Functional studies of HP have been limited by the absence of an experimental system that authentically mimics disease development. We therefore developed a novel transgenic murine model system using wild-type (WT) human PRSS1 or two HP-associated mutants (R122H and N29I) to determine whether expression of human cationic trypsinogen in murine acinar cells promotes pancreatitis. The rat elastase promoter was used to target transgene expression to pancreatic acinar cells in three transgenic strains that were generated: Tg(Ela-PRSS1)NV, Tg(Ela-PRSS1*R122H)NV and Tg(Ela-PRSS1*N29I)NV. Mice were analysed histologically, immunohistochemically and biochemically. We found that transgene expression is restricted to pancreatic acinar cells and transgenic PRSS1 proteins are targeted to the pancreatic secretory pathway. Animals from all transgenic strains developed pancreatitis characterised by acinar cell vacuolisation, inflammatory infiltrates and fibrosis. Transgenic animals also developed more severe pancreatitis upon treatment with low-dose cerulein than controls, displaying significantly higher scores for oedema, inflammation and overall histopathology. Expression of PRSS1, WT or mutant, in acinar cells increased apoptosis in pancreatic tissues and isolated acinar cells. Moreover, studies of isolated acinar cells demonstrated that transgene expression promotes apoptosis rather than necrosis. We therefore

  12. Attachment behaviors in mothers of premature infants: a descriptive study in Thai mothers.

    Science.gov (United States)

    Tilokskulchai, Fongcum; Phatthanasiriwethin, Sopida; Vichitsukon, Kannikar; Serisathien, Yaowalak

    2002-12-01

    Prematurity and the associated maternal-infant separation after birth can affect the attachment process. The role of nurses in facilitating the process of attachment should be based on an understanding of these behaviors. This descriptive study explored the attachment behaviors demonstrated by mothers during their first visit with their premature infant in the neonatal care unit. The results revealed that all mothers demonstrated most attachment behaviors (ie, inspection, facial expression, touching, verbal expression, and eye-to-eye contact) except holding during their first visit. However, some mothers spent little time with their infant. The findings suggest that nurses should encourage mothers to interact with their infants in order to enhance maternal-infant attachment.

  13. Gross morphological changes in premature and post mature human plancentae

    International Nuclear Information System (INIS)

    Sherin, F.; Afzal, E.; Seema, N.

    2015-01-01

    Placenta is a valuable tool for maternal and foetal diseases. Gross pathological changes are seen in the placenta of many disorders of pregnancy, which are associated with high perinatal morbidity and mortality. This study was conducted with the aim to compare the morphological features of preterm, term and post term placentae in our setup. Methods: This cross sectional study was conducted on 150 placentae: 50 were from normal (term) pregnancies considered as control (delivered between 37 to 42 weeks of gestation.), 50 from premature pregnancies (gestational age between 35-37 weeks) from mothers having hypertensive disorders of pregnancy, and 50 from post mature pregnancies (gestational age more than 42 weeks). The placentae were collected from Department of Obstetrics and Gynaecology, Khyber Teaching Hospital, Peshawar, through purposive sampling. Placentae were examined in the department of Anatomy, Khyber Medical College Peshawar. Results: In gross morphological features of placentae (weight and diameter) showed significant (p<0.001) among the groups Conclusion: In was concluded that the hypertensive disorders of the pregnancy adversely influence the morphology of placenta, which leads to the premature delivery. (author)

  14. Follow-up study on premature infants with and without retinopathy of prematurity.

    OpenAIRE

    Robinson, R; O'Keefe, M

    1993-01-01

    The ocular complications in population of 131 premature infants, with and without retinopathy of prematurity (ROP) are reported. An increased incidence of strabismus (20% with ROP and 25% without ROP) and myopia (27.5% with ROP and 8.8% without ROP) was shown. Significant visual loss occurred in 10.7% overall, increasing to 35% with stage 3 disease and 100% with stage 4. With the increased survival rate of premature infants, the relevance to future management of this expanding group of young ...

  15. Expression of RNA virus proteins by RNA polymerase II dependent expression plasmids is hindered at multiple steps

    Directory of Open Access Journals (Sweden)

    Überla Klaus

    2007-06-01

    Full Text Available Abstract Background Proteins of human and animal viruses are frequently expressed from RNA polymerase II dependent expression cassettes to study protein function and to develop gene-based vaccines. Initial attempts to express the G protein of vesicular stomatitis virus (VSV and the F protein of respiratory syncytial virus (RSV by eukaryotic promoters revealed restrictions at several steps of gene expression. Results Insertion of an intron flanked by exonic sequences 5'-terminal to the open reading frames (ORF of VSV-G and RSV-F led to detectable cytoplasmic mRNA levels of both genes. While the exonic sequences were sufficient to stabilise the VSV-G mRNA, cytoplasmic mRNA levels of RSV-F were dependent on the presence of a functional intron. Cytoplasmic VSV-G mRNA levels led to readily detectable levels of VSV-G protein, whereas RSV-F protein expression remained undetectable. However, RSV-F expression was observed after mutating two of four consensus sites for polyadenylation present in the RSV-F ORF. Expression levels could be further enhanced by codon optimisation. Conclusion Insufficient cytoplasmic mRNA levels and premature polyadenylation prevent expression of RSV-F by RNA polymerase II dependent expression plasmids. Since RSV replicates in the cytoplasm, the presence of premature polyadenylation sites and elements leading to nuclear instability should not interfere with RSV-F expression during virus replication. The molecular mechanisms responsible for the destabilisation of the RSV-F and VSV-G mRNAs and the different requirements for their rescue by insertion of an intron remain to be defined.

  16. Premature pubarche is niet altijd onschuldig

    NARCIS (Netherlands)

    Backes, Manouk; Zwaveling-Soonawala, Nitash; Kamp, Gerdine A.

    2012-01-01

    Premature pubarche is defined as growth of pubic hair before the age of 8 years in girls and 9 years in boys. In most cases, it is caused by premature adrenarche, which is a premature increased synthesis of androgens in the adrenal gland and is considered to be relatively harmless. Premature

  17. Human Milk Feeding as a Protective Factor for Retinopathy of Prematurity: A Meta-analysis.

    Science.gov (United States)

    Zhou, Jianguo; Shukla, Vivek V; John, Denny; Chen, Chao

    2015-12-01

    Studies have suggested that human milk feeding decreases the incidence of retinopathy of prematurity (ROP); however, conflicting results have been reported. The aim of this meta-analysis was to pool currently available data on incidence of ROP in infants fed human milk versus formula. Medline, PubMed, and EBSCO were searched for articles published through February 2015. Longitudinal studies comparing the incidence of ROP in infants who were fed human milk and formula were selected. Studies involving donor milk were not included. Two independent reviewers conducted the searches and extracted data. Meta-analysis used odds ratios (ORs), and subgroup analyses were performed. Five studies with 2208 preterm infants were included. Searches including various proportions of human milk versus formula, any-stage ROP, and severe ROP were defined to pool data for analyses. For any-stage ROP, the ORs (95% confidence intervals [CIs]) were as follows: exclusive human milk versus any formula, 0.29 (0.12 to 0.72); mainly human milk versus mainly formula, 0.51 (0.26 to 1.03); any human milk versus exclusive formula, 0.54 (0.15 to 1.96); and exclusive human milk versus exclusive formula, 0.25 (0.13 to 0.49). For severe ROP, they were 0.11 (0.04 to 0.30), 0.16 (0.06 to 0.43), 0.42 (0.08 to 2.18), and 0.10 (0.04 to 0.29), respectively. Prospective randomized studies being impossible because of ethical issues, we chose observational studies for analysis. A few studies involving subgroup analyses presented high heterogeneity. Based on current limited evidence, in very preterm newborns, human milk feeding potentially plays a protective role in preventing any-stage ROP and severe ROP. Copyright © 2015 by the American Academy of Pediatrics.

  18. Open bite in prematurely born children.

    Science.gov (United States)

    Harila, V; Heikkinen, T; Grön, M; Alvesalo, L

    2007-01-01

    The aims of this study were to: examine the expression of open bite in prematurely born children and discuss the etiological factors that may lead to bite it. The subjects were 328 prematurely born (cross-sectional study of the Collaborative Perinatal Project in the 1960s and 1970s. Dental documents, including casts and photographs, were taken once at the age of 6-12 years in the mixed dentition. The occlusion was recorded by examining and measuring the hard stone casts. Vertical open bite was recorded only for full erupted teeth. The statistical method used was chi-square analysis. Significant differences in the incidence of anterior open bite (from left to right canine) was found between the preterm and control groups and between gender and ethnic groups. The prevalence of anterior open bite was nearly 9% in the preterm group and almost 7% in the control group. African Americans (9%) had a significantly greater incidence of open bite than Caucasians (3%; Pbite than boys (8% vs 6%; Pbite was increased--especially in preterm African American boys compared to controls (11% vs 8%). The results show differences in the development of anterior open bite between ethnic and gender groups. Premature birth may also influence dental occlusal development. Of importance are the patient's: general health condition; respiratory infections; inadequate nasal- and mouth-breathing; oral habits; and other medical problems. Preterm children may be relatively more predisposed to etiological factors for the development of anterior open bite.

  19. Cigarette smoking during pregnancy regulates the expression of specific nicotinic acetylcholine receptor (nAChR) subunits in the human placenta

    Energy Technology Data Exchange (ETDEWEB)

    Machaalani, R., E-mail: rita.machaalani@sydney.edu.au [Department of Medicine, The University of Sydney, NSW 2006 (Australia); Bosch Institute, The University of Sydney, NSW 2006 (Australia); The Children' s Hospital at Westmead, NSW 2145 (Australia); Ghazavi, E. [Bosch Institute, The University of Sydney, NSW 2006 (Australia); School of Medical Sciences (Pharmacology), The University of Sydney, NSW 2006 (Australia); Hinton, T. [School of Medical Sciences (Pharmacology), The University of Sydney, NSW 2006 (Australia); Waters, K.A. [Department of Medicine, The University of Sydney, NSW 2006 (Australia); The Children' s Hospital at Westmead, NSW 2145 (Australia); Hennessy, A. [School of Medicine, University of Western Sydney, NSW 2751 (Australia); Heart Research Institute, 7 Eliza St Newtown, NSW 2042 (Australia)

    2014-05-01

    Smoking during pregnancy is associated with low birth weight, premature delivery, and neonatal morbidity and mortality. Nicotine, a major pathogenic compound of cigarette smoke, binds to the nicotinic acetylcholine receptors (nAChRs). A total of 16 nAChR subunits have been identified in mammals (9 α, 4 β, and 1 δ, γ and ε subunits). The effect of cigarette smoking on the expression of these subunits in the placenta has not yet been determined, thus constituting the aim of this study. Using RT-qPCR and western blotting, this study investigated all 16 mammalian nAChR subunits in the normal healthy human placenta, and compared mRNA and protein expressions in the placentas from smokers (n = 8) to controls (n = 8). Our data show that all 16 subunit mRNAs are expressed in the normal, non-diseased human placenta and that the expression of α2, α3, α4, α9, β2 and β4 subunits is greater than the other subunits. For mRNA, cigarette smoke exposure was associated with increased expression of the α9 subunit, and decreased expression of the δ subunit. At the protein level, expression of both α9 and δ was increased. Thus, cigarette smoking in pregnancy is sufficient to regulate nAChR subunits in the placenta, specifically α9 and δ subunits, and could contribute to the adverse effects of vasoconstriction and decreased re-epithelialisation (α9), and increased calcification and apoptosis (δ), seen in the placentas of smoking women. - Highlights: • All 16 mammalian nAChR subunits are expressed in the human placenta. • Cigarette smoking increases α9 mRNA and protein in the placenta. • Cigarette smoking decreases δ mRNA but increases δ protein in the placenta.

  20. Cigarette smoking during pregnancy regulates the expression of specific nicotinic acetylcholine receptor (nAChR) subunits in the human placenta

    International Nuclear Information System (INIS)

    Machaalani, R.; Ghazavi, E.; Hinton, T.; Waters, K.A.; Hennessy, A.

    2014-01-01

    Smoking during pregnancy is associated with low birth weight, premature delivery, and neonatal morbidity and mortality. Nicotine, a major pathogenic compound of cigarette smoke, binds to the nicotinic acetylcholine receptors (nAChRs). A total of 16 nAChR subunits have been identified in mammals (9 α, 4 β, and 1 δ, γ and ε subunits). The effect of cigarette smoking on the expression of these subunits in the placenta has not yet been determined, thus constituting the aim of this study. Using RT-qPCR and western blotting, this study investigated all 16 mammalian nAChR subunits in the normal healthy human placenta, and compared mRNA and protein expressions in the placentas from smokers (n = 8) to controls (n = 8). Our data show that all 16 subunit mRNAs are expressed in the normal, non-diseased human placenta and that the expression of α2, α3, α4, α9, β2 and β4 subunits is greater than the other subunits. For mRNA, cigarette smoke exposure was associated with increased expression of the α9 subunit, and decreased expression of the δ subunit. At the protein level, expression of both α9 and δ was increased. Thus, cigarette smoking in pregnancy is sufficient to regulate nAChR subunits in the placenta, specifically α9 and δ subunits, and could contribute to the adverse effects of vasoconstriction and decreased re-epithelialisation (α9), and increased calcification and apoptosis (δ), seen in the placentas of smoking women. - Highlights: • All 16 mammalian nAChR subunits are expressed in the human placenta. • Cigarette smoking increases α9 mRNA and protein in the placenta. • Cigarette smoking decreases δ mRNA but increases δ protein in the placenta

  1. Histological evidence of oxidative stress and premature senescence in preterm premature rupture of the human fetal membranes recapitulated in vitro.

    Science.gov (United States)

    Menon, Ramkumar; Boldogh, Istvan; Hawkins, Hal K; Woodson, Michael; Polettini, Jossimara; Syed, Tariq Ali; Fortunato, Stephen J; Saade, George R; Papaconstantinou, John; Taylor, Robert N

    2014-06-01

    Preterm prelabor rupture of the membranes (pPROM) may lead to preterm births (PTBs). We investigated premature senescence of fetal membranes in women with pPROM and spontaneous PTB with intact membranes (PTBs, and term births. Term fetal membranes were exposed to cigarette smoke extract to induce oxidative stress. Western blots documented p-p53 and p-p38 MAPK. Transmission electron microscopy assessed cellular morphologic features in clinical and cigarette smoke extract-treated membranes. A total of 80% of pPROM cells and >60% of term cells were positive for all three senescence phenotype markers, and concentrations were higher than in PTBs (P PTBs. Histologic and biochemical resemblance of pPROM and term membranes suggests premature senescence of the membranes is a mechanistic feature in pPROM, and this can be phenocopied in an in vitro model. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  2. Prematures with and without Regressed Retinopathy of Prematurity: Comparison of Long-Term (6-10 Years) Ophthalmological Morbidity.

    Science.gov (United States)

    Cats, Bernard P.; Tan, Karel E. W. P.

    Reporting long-term ophthalmologic sequelae among ex-prematures at 6 to 10 years of age, this study compares 42 ex-premature infants who had had regressed forms of retinopathy of prematurity (ROP) during the neonatal period with 42 matched non-ROP ex-premature controls at 6 to 10 years of age. Subjects were subdivided into four groups: (1) ROP…

  3. Therapeutic doses of doxorubicin induce premature senescence of human mesenchymal stem cells derived from menstrual blood, bone marrow and adipose tissue.

    Science.gov (United States)

    Kozhukharova, Irina; Zemelko, Victoria; Kovaleva, Zoya; Alekseenko, Larisa; Lyublinskaya, Olga; Nikolsky, Nikolay

    2018-03-01

    Doxorubicin (Dox) is an effective anticancer drug with known activity against a wide spectrum of malignancies, hematologic malignancies in particular. Despite extensive clinical use, the mechanisms of its side effects and negative action on normal cells remain under study. The aim of this study was to investigate the effect of Dox on cultured human mesenchymal stem cells (MSCs) derived from menstrual blood (eMSCs), bone marrow (BMSCs) and adipose tissue (AMSCs). Dox treatment in high doses decreased the survival of MSCs in a dose-dependent manner. Clinically relevant low doses of Dox induced premature senescence of eMSCs, BMSCs and AMSCs, but did not kill the cells. Dox caused cell cycle arrest and formation of γ-H2AX foci, and increased the number of SA-β-gal-positive cells. BMSCs entered premature senescence earlier than other MSCs. It has been reported that neural-like cells differentiated from MSCs of various origins are more sensitive to Dox than their parent cells. Dox-treated differentiated MSCs exhibited lower viability and earlier generation of γ-H2AX foci. Dox administration inhibited secretory activity in neural-like cells. These findings suggest that a clinically relevant Dox dose damages cultured MSCs, inducing their premature senescence. MSCs are more resistant to this damage than differentiated cells.

  4. Premature ovarian failure

    OpenAIRE

    Pacheco, José

    2011-01-01

    Premature ovarian failure is characterized by secondary amenorrhea affecting a woman before the age of 40, leading to hypoestrogenism, infertility, and consequences of premature menopause, such as osteoporosis, cardiovascular disease, neurovegetative alterations, and others. Follicular exhaustion is due to either follicles shortage or oocytes accelerated destruction. Main causes are genetic, autoimmune and iatrogenic. Among genetic causes Xq and Xp deletions, translocations, numeric aberratio...

  5. The Relationship between Motor Delays and Language Development in Very Low Birthweight Premature Children at 18 Months Corrected Age

    Science.gov (United States)

    Ross, Gail; Demaria, Rebecca; Yap, Vivien

    2018-01-01

    Purpose: The aim of this study is to determine if there is a specific association between motor delays and receptive and expressive language function, respectively, in prematurely born children. Method: Retrospective data review: 126 premature children = 1,250-g birthweight from English-speaking families were evaluated on motor development…

  6. Poly(I:C) induces expressions of MMP-1, -2, and -3 through various signaling pathways including IRF3 in human skin fibroblasts.

    Science.gov (United States)

    Yao, Cheng; Lee, Dong Hun; Oh, Jang-Hee; Kim, Min-Kyoung; Kim, Kyu Han; Park, Chi-Hyun; Chung, Jin Ho

    2015-10-01

    Ultraviolet (UV) irradiation can result in premature skin aging (photoaging) which is characterized by decreased expression of collagen and increased expression of matrix metalloproteinases (MMPs). Double-stranded RNAs (dsRNAs) can be generated at various conditions including virally infected cells or UV-damaged skin cells. Recent studies have shown that a synthetic dsRNA, polyinosinic-polycytidylic acid (poly(I:C)), can reduce procollagen expression in human skin fibroblasts. However, little is known about the effect of poly(I:C) on the expression of MMPs in skin fibroblasts and its underlying mechanisms. We examined the effect of poly(I:C) on MMP-1, -2, and -3 expressions in human skin fibroblasts. Then, we further explored the underlying signaling pathways involved in the processes. Human skin fibroblasts were treated with poly(I:C) for the indicated times in the presence or the absence of various chemical inhibitors or small interfering RNAs (siRNAs) at the indicated concentrations. Protein and mRNA levels of various target molecules were examined by Western blotting and quantitative real-time PCR, respectively. Poly(I:C) induced MMP-1, -2, and -3 expressions, which were dependent on TLR3. Poly(I:C) also induced activations of the mitogen-activated protein kinases (MAPKs), the nuclear factor-kappaB (NF-κB) and the interferon regulatory factor 3 (IRF3) pathways. By using specific inhibitors, we found that poly(I:C)-induced expressions of MMP-1, -2, and -3 were differentially regulated by these signaling pathways. In particular, we found that the inhibition of IRF3 signaling pathways attenuated poly(I:C)-induced expressions of all the three MMPs. Our data show that the expressions of MMP-1, -2, and -3 are induced by poly(I:C) through various signaling pathways in human skin fibroblasts and suggest that TLR3 and/or IRF3 may be good targets for regulating the expressions of MMP-1, -2, and -3 induced by dsRNAs. Copyright © 2015 Elsevier Ireland Ltd. All rights

  7. Premature emphysema in AIDS

    International Nuclear Information System (INIS)

    Kuhlman, J.E.; Fishman, E.K.; Zerhouni, E.A.; Knowles, M.

    1988-01-01

    The CT scans of 55 patients with acquired immunodeficiency syndrome (AIDS) were reviewed for evidence of pulmonary emphysema. While the average age of patients in this series was 38 years, 25 of the 55 patients, or 45%, demonstrated CT evidence of emphysema. CT findings suggestive of emphysema included areas of low-attenuation, blebs and/or vascular disruption. The authors conclude there is an increased incidence of CT-detectable pulmonary emphysema that is premature for age in patients with AIDS. Destruction of pulmonary parenchyma may represent the response of the lung to repeated pulmonary infections or may be a direct result of the human immunodeficiency virus

  8. Higher O-GlcNAc Levels Are Associated with Defects in Progenitor Proliferation and Premature Neuronal Differentiation during in-Vitro Human Embryonic Cortical Neurogenesis

    Directory of Open Access Journals (Sweden)

    Shama Parween

    2017-12-01

    Full Text Available The nutrient responsive O-GlcNAcylation is a dynamic post-translational protein modification found on several nucleocytoplasmic proteins. Previous studies have suggested that hyperglycemia induces the levels of total O-GlcNAcylation inside the cells. Hyperglycemia mediated increase in protein O-GlcNAcylation has been shown to be responsible for various pathologies including insulin resistance and Alzheimer's disease. Since maternal hyperglycemia during pregnancy is associated with adverse neurodevelopmental outcomes in the offspring, it is intriguing to identify the effect of increased protein O-GlcNAcylation on embryonic neurogenesis. Herein using human embryonic stem cells (hESCs as model, we show that increased levels of total O-GlcNAc is associated with decreased neural progenitor proliferation and premature differentiation of cortical neurons, reduced AKT phosphorylation, increased apoptosis and defects in the expression of various regulators of embryonic corticogenesis. As defects in proliferation and differentiation during neurodevelopment are common features of various neurodevelopmental disorders, increased O-GlcNAcylation could be one mechanism responsible for defective neurodevelopmental outcomes in metabolically compromised pregnancies such as diabetes.

  9. Altered Decorin and Smad Expression in Human Fetal Membranes in PPROM1

    Science.gov (United States)

    Horgan, Casie E.; Roumimper, Hailey; Tucker, Richard; Lechner, Beatrice E.

    2014-01-01

    ABSTRACT Humans with Ehlers-Danlos syndrome, a subtype of which is caused by abnormal decorin expression, are at increased risk of preterm birth due to preterm premature rupture of fetal membranes (PPROM). In the mouse model, the absence of decorin leads to fetal membrane abnormalities, preterm birth, and dysregulation of decorin's downstream pathway components, including the transcription factor p-Smad-2. However, the role of decorin and p-Smad-2 in idiopathic human PPROM is unknown. Fetal membranes from 20–25 pregnancies per group were obtained as a cross-sectional sample of births at one institution between January 2010 and December 2012. The groups were term, preterm without PPROM, and preterm with PPROM. Immunohistochemical analysis of fetal membranes was performed for decorin and p-Smad-2 using localization and quantification assessment. Decorin expression is developmentally regulated in fetal membranes and is decreased in preterm birth with PPROM compared to preterm birth without PPROM. In preterm with PPROM samples, the presence of infection is associated with significant decorin downregulation compared to preterm with PPROM samples without infection. The preterm with PPROM group exhibited decreased p-Smad-2 staining compared to both the term controls and the preterm-without-PPROM group. Our findings suggest that dysregulation of decorin and its downstream pathway component p-Smad-2 occurs in fetal membranes during the second trimester in pathological pregnancies, thus supporting a role for decorin and p-Smad-2 in the pathophysiology of fetal membranes and adverse pregnancy outcomes. These findings may lead to the discovery of new targets for the diagnosis and treatment of PPROM. PMID:25232019

  10. Family Perspectives on Prematurity

    Science.gov (United States)

    Zero to Three (J), 2003

    2003-01-01

    In this article, seven families describe their experiences giving birth to and raising a premature baby. Their perspectives vary, one from another, and shift over time, depending on each family's circumstances and the baby's developmental course. Experiences discussed include premature labor, medical interventions and the NICU, bringing the baby…

  11. Prenatal stress, prematurity and asthma

    Science.gov (United States)

    Medsker, Brock; Forno, Erick; Simhan, Hyagriv; Celedón, Juan C.

    2016-01-01

    Asthma is the most common chronic disease of childhood, affecting millions of children in the U.S. and worldwide. Prematurity is a risk factor for asthma, and certain ethnic or racial minorities such as Puerto Ricans and non-Hispanic Blacks are disproportionately affected by both prematurity and asthma. In this review, we examine current evidence to support maternal psychosocial stress as a putative link between prematurity and asthma, while also focusing on disruption of the hypothalamic-pituitary-adrenal (HPA) axis and immune responses as potential underlying mechanisms for stress-induced “premature asthma”. Prenatal stress may not only cause abnormalities in the HPA axis but also epigenetic changes in the fetal glucocorticoid receptor gene (NR3C1), leading to impaired glucocorticoid metabolism. Moreover, maternal stress can alter fetal cytokine balance, favoring Th2 (allergic) immune responses characteristic of atopic asthma: IL-6, which has been associated with premature labor, can promote Th2 responses by stimulating production of IL-4 and IL-13. Given a link among stress, prematurity, and asthma, future research should include birth cohorts aimed at confirming and better characterizing “premature asthma”. If confirmed, clinical trials of prenatal maternal stress reduction would be warranted to reduce the burden of these common co-morbidities. While awaiting the results of such studies, sound policies to prevent domestic and community violence (e.g. from firearms) are justified, not only by public safety but also by growing evidence of detrimental effects of violence-induced stress on psychiatric and somatic health. PMID:26676148

  12. ATM-deficient human fibroblast cells are resistant to low levels of DNA double-strand break induced apoptosis and subsequently undergo drug-induced premature senescence

    International Nuclear Information System (INIS)

    Park, Jun; Jo, Yong Hwa; Cho, Chang Hoon; Choe, Wonchae; Kang, Insug; Baik, Hyung Hwan; Yoon, Kyung-Sik

    2013-01-01

    Highlights: ► A-T cells were not hypersensitive to low levels of DNA DSBs. ► A-T cells have enhanced Akt but defect in activation of p53 and apoptotic proteins. ► A-T cells underwent premature senescence after DNA damage accumulated. ► Chemotherapeutic effect in cancer therapy may be associated with premature senescence. -- Abstract: DNA DSBs are induced by IR or radiomimetic drugs such as doxorubicin. It has been indicated that cells from ataxia-telangiectasia patients are highly sensitive to radiation due to defects in DNA repair, but whether they have impairment in apoptosis has not been fully elucidated. A-T cells showed increased sensitivity to high levels of DNA damage, however, they were more resistant to low doses. Normal cells treated with combination of KU55933, a specific ATM kinase inhibitor, and doxorubicin showed increased resistance as they do in a similar manner to A-T cells. A-T cells have higher viability but more DNA breaks, in addition, the activations of p53 and apoptotic proteins (Bax and caspase-3) were deficient, but Akt expression was enhanced. A-T cells subsequently underwent premature senescence after treatment with a low dose of doxorubicin, which was confirmed by G2 accumulation, senescent morphology, and SA-β-gal positive until 15 days repair incubation. Finally, A-T cells are radio-resistant at low doses due to its defectiveness in detecting DNA damage and apoptosis, but the accumulation of DNA damage leads cells to premature senescence.

  13. IL-21 Receptor Expression in Human Tendinopathy

    Directory of Open Access Journals (Sweden)

    Abigail L. Campbell

    2014-01-01

    Full Text Available The pathogenetic mechanisms underlying tendinopathy remain unclear, with much debate as to whether inflammation or degradation has the prominent role. Increasing evidence points toward an early inflammatory infiltrate and associated inflammatory cytokine production in human and animal models of tendon disease. The IL-21/IL-21R axis is a proinflammatory cytokine complex that has been associated with chronic inflammatory diseases including rheumatoid arthritis and inflammatory bowel disease. This project aimed to investigate the role and expression of the cytokine/receptor pair IL-21/IL-21R in human tendinopathy. We found significantly elevated expression of IL-21 receptor message and protein in human tendon samples but found no convincing evidence of the presence of IL-21 at message or protein level. The level of expression of IL-21R message/protein in human tenocytes was significantly upregulated by proinflammatory cytokines (TNFα/IL-1β in vitro. These findings demonstrate that IL-21R is present in early human tendinopathy mainly expressed by tenocytes and macrophages. Despite a lack of IL-21 expression, these data again suggest that early tendinopathy has an inflammatory/cytokine phenotype, which may provide novel translational targets in the treatment of tendinopathy.

  14. The cost of lost productivity due to premature cancer-related mortality: an economic measure of the cancer burden.

    Science.gov (United States)

    Hanly, Paul A; Sharp, Linda

    2014-03-26

    Most measures of the cancer burden take a public health perspective. Cancer also has a significant economic impact on society. To assess this economic burden, we estimated years of potential productive life lost (YPPLL) and costs of lost productivity due to premature cancer-related mortality in Ireland. All cancers combined and the 10 sites accounting for most deaths in men and in women were considered. To compute YPPLL, deaths in 5-year age-bands between 15 and 64 years were multiplied by average working-life expectancy. Valuation of costs, using the human capital approach, involved multiplying YPPLL by age-and-gender specific gross wages, and adjusting for unemployment and workforce participation. Sensitivity analyses were conducted around retirement age and wage growth, labour force participation, employment and discount rates, and to explore the impact of including household production and caring costs. Costs were expressed in €2009. Total YPPLL was lower in men than women (men = 10,873; women = 12,119). Premature cancer-related mortality costs were higher in men (men: total cost = €332 million, cost/death = €290,172, cost/YPPLL = €30,558; women: total cost = €177 million, cost/death = €159,959, cost/YPPLL = €14,628). Lung cancer had the highest premature mortality cost (€84.0 million; 16.5% of total costs), followed by cancers of the colorectum (€49.6 million; 9.7%), breast (€49.4 million; 9.7%) and brain & CNS (€42.4 million: 8.3%). The total economic cost of premature cancer-related mortality in Ireland amounted to €509.5 million or 0.3% of gross domestic product. An increase of one year in the retirement age increased the total all-cancer premature mortality cost by 9.9% for men and 5.9% for women. The inclusion of household production and caring costs increased the total cost to €945.7 million. Lost productivity costs due to cancer-related premature mortality are significant. The higher premature mortality cost in males than

  15. Comparison of the Effect of Two Human Milk Fortifiers on Clinical Outcomes in Premature Infants

    Directory of Open Access Journals (Sweden)

    Melissa Thoene

    2014-01-01

    Full Text Available The use of human milk fortifiers (HMF helps to meet the high nutritional requirements of the human milk-fed premature infant. Previously available powdered products have not met the protein requirements of the preterm infant population and many neonatologists add powder protein modulars to help meet protein needs. The use of powdered products is discouraged in neonatal intensive care units (NICU due to concern for invasive infection. The use of a commercially available acidified liquid product with higher protein content was implemented to address these two concerns. During the course of this implementation, poor growth and clinically significant acidosis of infants on Acidified Liquid HMF (ALHMF was observed. The purpose of this study was to quantify those observations by comparing infant outcomes between groups receiving the ALHMF vs. infants receiving powdered HMF (PHMF. A retrospective chart review compared outcomes of human milk-fed premature infants <2000 g receiving the ALHMF (n = 23 and the PHMF (n = 46. Infant growth, enteral feeding tolerance and provision, and incidence of necrotizing enterocolitis (NEC, metabolic acidosis, and diaper dermatitis were compared between the two groups. No infants were excluded from this study based on acuity. Use of ALHMF resulted in a higher incidence of metabolic acidosis (p = 0.002. Growth while on HMF as measured in both g/kg/day (10.59 vs. 15.37, p < 0.0001 and in g/day (23.66 vs. 31.27, p = 0.0001 was slower in the ALHMF group, on increased mean cal/kg/day (128.7 vs. 117.3, p = 0.13 with nearly twice as many infants on the ALHMF requiring increased fortification of enteral feedings beyond 24 cal/ounce to promote adequate growth (48% vs. 26%, p = 0.10. Although we were not powered to study NEC as a primary outcome, NEC was significantly increased in the ALHMF group. (13% vs. 0%, p = 0.03. Use of a LHMF in an unrestricted NICU population resulted in an increase in clinical complications within a high

  16. Human Eosinophils Express Functional CCR7

    Science.gov (United States)

    Ueki, Shigeharu; Estanislau, Jessica; Weller, Peter F.

    2013-01-01

    Human eosinophils display directed chemotactic activity toward an array of soluble chemokines. Eosinophils have been observed to migrate to draining lymph nodes in experimental models of allergic inflammation, yet it is unknown whether eosinophils express CCR7, a key chemokine receptor in coordinating leukocyte trafficking to lymph nodes. The purpose of this study is to demonstrate expression of CCR7 by human eosinophils and functional responses to CCL19 and CCL21, the known ligands of CCR7. Human eosinophils were purified by negative selection from healthy donors. CCR7 expression of freshly purified, unstimulated eosinophils and of IL-5–primed eosinophils was determined by flow cytometry and Western blot. Chemotaxis to CCL19 and CCL21 was measured in transwell assays. Shape changes to CCL19 and CCL21 were analyzed by flow cytometry and microscopy. Calcium fluxes of fluo-4 AM–loaded eosinophils were recorded by flow cytometry after chemokine stimulation. ERK phosphorylation of CCL19- and CCL21-stimulated eosinophils was measured by Western blot and Luminex assay. Human eosinophils expressed CCR7 as demonstrated by flow cytometry and Western blots. Eosinophils exhibited detectable cell surface expression of CCR7. IL-5–primed eosinophils exhibited chemotaxis toward CCL19 and CCL21 in a dose-dependent fashion. Upon stimulation with CCL19 or CCL21, IL-5–primed eosinophils demonstrated dose-dependent shape changes with polarization of F-actin and exhibited calcium influxes. Finally, primed eosinophils stimulated with CCL19 or CCL21 exhibited increased phosphorylation of ERK in response to both CCR7 ligands. We demonstrate that human eosinophils express CCR7 and have multipotent responses to the known ligands of CCR7. PMID:23449735

  17. Regenerating human muscle fibres express GLUT3 protein

    DEFF Research Database (Denmark)

    Gaster, M; Beck-Nielsen, H; Schrøder, H D

    2002-01-01

    The presence of the GLUT3 glucose transporter protein in human muscle cells is a matter of debate. The present study was designed to establish whether GLUT3 is expressed in mature human skeletal muscle fibres and, if so, whether its expression changes under different conditions, such as metabolic...... muscle fibres, nor did metabolic stress, training or de- and re-innervation induce GLUT3 expression, while a few GLUT3 expressing fibres were seen in some cases of polymyositis. In contrast, GLUT4 was expressed in all investigated muscle fibres. GLUT3 immunoreactivity was found in perineural...... and endoneural cells, indicating that GLUT3 is important for glucose transport into nerves through the perineurium. Taken together, these data suggest that GLUT3 expression is restricted to regenerating muscle fibres and nerves in adult human muscle. Although the significance of GLUT3 in adult human muscle...

  18. Your Premature Baby: Low Birthweight

    Science.gov (United States)

    ... volunteer leader Partner Spotlight Become a partner World Prematurity Day What's happening in your area Find out ... to remove damaged parts of intestine. Retinopathy of prematurity (also called ROP) . ROP affects blood vessels in ...

  19. Health Issues of Premature Babies

    Science.gov (United States)

    ... they leave the hospital for home. Retinopathy of Prematurity (ROP) What It Is: ROP is an eye ... sometimes seen in preterm babies include anemia of prematurity (a low red blood cell count) and heart ...

  20. Helicobacter pylori-induced premature senescence of extragastric cells may contribute to chronic skin diseases.

    Science.gov (United States)

    Lewinska, Anna; Wnuk, Maciej

    2017-04-01

    Helicobacter pylori, one of the most frequently observed bacterium in the human intestinal flora, has been widely studied since Marshall and Warren documented a link between the presence of H. pylori in the gastrointestinal tract and gastritis and gastric ulcers. Interestingly, H. pylori has also been found in several other epithelial tissues, including the eyes, ears, nose and skin that may have direct or indirect effects on host physiology and may contribute to extragastric diseases, e.g. chronic skin diseases. More recently, it has been shown that H. pylori cytotoxin CagA expression induces cellular senescence of human gastric nonpolarized epithelial cells that may lead to gastrointestinal disorders and systemic inflammation. Here, we hypothesize that also chronic skin diseases may be promoted by stress-induced premature senescence (SIPS) of skin cells, namely fibroblasts and keratinocytes, stimulated with H. pylori cytotoxins. Future studies involving cell culture models and clinical specimens are needed to verify the involvement of H. pylori in SIPS-based chronic skin diseases.

  1. Positive selection on gene expression in the human brain

    DEFF Research Database (Denmark)

    Khaitovich, Philipp; Tang, Kun; Franz, Henriette

    2006-01-01

    Recent work has shown that the expression levels of genes transcribed in the brains of humans and chimpanzees have changed less than those of genes transcribed in other tissues [1] . However, when gene expression changes are mapped onto the evolutionary lineage in which they occurred, the brain...... shows more changes than other tissues in the human lineage compared to the chimpanzee lineage [1] , [2] and [3] . There are two possible explanations for this: either positive selection drove more gene expression changes to fixation in the human brain than in the chimpanzee brain, or genes expressed...... in the brain experienced less purifying selection in humans than in chimpanzees, i.e. gene expression in the human brain is functionally less constrained. The first scenario would be supported if genes that changed their expression in the brain in the human lineage showed more selective sweeps than other genes...

  2. Retinal vascular speed prematurity requiring treatment.

    Science.gov (United States)

    Solans Pérez de Larraya, Ana M; Ortega Molina, José M; Fernández, José Uberos; Escudero Gómez, Júlia; Salgado Miranda, Andrés D; Chaves Samaniego, Maria J; García Serrano, José L

    2018-03-01

    To analyse the speed of temporal retinal vascularisation in preterm infants included in the screening programme for retinopathy of prematurity. A total of 185 premature infants were studied retrospectively between 2000 and 2017 in San Cecilio University Hospital of Granada, Spain. The method of binocular indirect ophthalmoscopy with indentation was used for the examination. The horizontal disc diameter was used as a unit of length. Speed of temporal retinal vascularisation (disc diameter/week) was calculated as the ratio between the extent of temporal retinal vascularisation (disc diameter) and the time in weeks. The weekly temporal retinal vascularisation (0-1.25 disc diameter/week, confidence interval) was significantly higher in no retinopathy of prematurity (0.73 ± 0.22 disc diameter/week) than in stage 1 retinopathy of prematurity (0.58 ± 0.22 disc diameter/week). It was also higher in stage 1 than in stages 2 (0.46 ± 0.14 disc diameter/week) and 3 of retinopathy of prematurity (0.36 ± 0.18 disc diameter/week). The rate of temporal retinal vascularisation (disc diameter/week) decreases when retinopathy of prematurity stage increases. The area under the receiver operating characteristic curve was 0.85 (95% confidence interval: 0.79-0.91) for retinopathy of prematurity requiring treatment versus not requiring treatment. The best discriminative cut-off point was a speed of retinal vascularisation prematurity may be required. However, before becoming a new standard of care for treatment, it requires careful documentation, with agreement between several ophthalmologists.

  3. Circulating hematopoietic stem cell count is a valuable predictor of prematurity complications in preterm newborns

    Directory of Open Access Journals (Sweden)

    Kotowski Maciej

    2012-09-01

    Full Text Available Abstract Background The frequency of preterm labour has risen over the last few years. Hence, there is growing interest in the identification of markers that may facilitate prediction and prevention of premature birth complications. Here, we studied the association of the number of circulating stem cell populations with the incidence of complications typical of prematurity. Methods The study groups consisted of 90 preterm (23–36 weeks of gestational age and 52 full-term (37–41 weeks infants. Non-hematopoietic stem cells (non-HSCs; CD45-lin-CD184+, enriched in very small embryonic-like stem cells (VSELs, expressing pluripotent (Oct-4, Nanog, early neural (β-III-tubulin, and oligodendrocyte lineage (Olig-1 genes as well as hematopoietic stem cells (HSCs; CD45+lin-CD184+, and circulating stem/progenitor cells (CSPCs; CD133+CD34+; CD133-CD34+ in association with characteristics of prematurity and preterm morbidity were analyzed in cord blood (CB and peripheral blood (PB until the sixth week after delivery. Phenotype analysis was performed using flow cytometry methods. Clonogenic assays suitable for detection of human hematopoietic progenitor cells were also applied. The quantitative parameters were compared between groups by the Mann–Whitney test and between time points by the Friedman test. Fisher’s exact test was used for qualitative variables. Results We found that the number of CB non-HSCs/VSELs is inversely associated with the birth weight of preterm infants. More notably, a high number of CB HSCs is strongly associated with a lower risk of prematurity complications including intraventricular hemorrhage, respiratory distress syndrome, infections, and anemia. The number of HSCs remains stable for the first six weeks of postnatal life. Besides, the number of CSPCs in CB is significantly higher in preterm infants than in full-term neonates (p  Conclusion We conclude that CB HSCs are markedly associated with the development of premature

  4. Transgenic expression of cyclooxygenase-2 (COX2) causes premature aging phenotypes in mice.

    Science.gov (United States)

    Kim, Joohwee; Vaish, Vivek; Feng, Mingxiao; Field, Kevin; Chatzistamou, Ioulia; Shim, Minsub

    2016-10-07

    Cyclooxygenase (COX) is a key enzyme in the biosynthesis of prostanoids, lipid signaling molecules that regulate various physiological processes. COX2, one of the isoforms of COX, is highly inducible in response to a wide variety of cellular and environmental stresses. Increased COX2 expression is thought to play a role in the pathogenesis of many age-related diseases. COX2 expression is also reported to be increased in the tissues of aged humans and mice, which suggests the involvement of COX2 in the aging process. However, it is not clear whether the increased COX2 expression is causal to or a result of aging. We have now addressed this question by creating an inducible COX2 transgenic mouse model. Here we show that post-natal expression of COX2 led to a panel of aging-related phenotypes. The expression of p16, p53, and phospho-H2AX was increased in the tissues of COX2 transgenic mice. Additionally, adult mouse lung fibroblasts from COX2 transgenic mice exhibited increased expression of the senescence-associated β-galactosidase. Our study reveals that the increased COX2 expression has an impact on the aging process and suggests that modulation of COX2 and its downstream signaling may be an approach for intervention of age-related disorders.

  5. [Development of premature children: caregivers' understanding according to the Bioecological Theory].

    Science.gov (United States)

    Lemos, Rayla Amaral; Veríssimo, Maria de La Ó Ramallo

    2015-12-01

    Understanding the conceptions of premature children caregivers on child development and associated factors. An exploratory-descriptive qualitative study of 12 families with children under three years of age. Interviews were submitted to thematic content analysis, systematized into the categories of Bioecological Theory of Human Development: Process, Person, Context and Time, and in the Functional Development category. There are concerns about impairment in the current and future development of a Person/child defined as fragile as a result of premature birth (Time dimension), minimized by the scope of observable competencies such as motor skills. The Context, especially family and health services, and Proximal Processes, described as one-way caregiver interactions, are considered determinants of development. Functional Development is considered a natural consequence and result of education. The support network is crucial, supporting or limiting care. Concerns about the development mobilize caregivers to stimulate the premature child/person and requests family and healthcare assistance.

  6. Cis-acting sequences from a human surfactant protein gene confer pulmonary-specific gene expression in transgenic mice

    Energy Technology Data Exchange (ETDEWEB)

    Korfhagen, T.R.; Glasser, S.W.; Wert, S.E.; Bruno, M.D.; Daugherty, C.C.; McNeish, J.D.; Stock, J.L.; Potter, S.S.; Whitsett, J.A. (Cincinnati College of Medicine, OH (USA))

    1990-08-01

    Pulmonary surfactant is produced in late gestation by developing type II epithelial cells lining the alveolar epithelium of the lung. Lack of surfactant at birth is associated with respiratory distress syndrome in premature infants. Surfactant protein C (SP-C) is a highly hydrophobic peptide isolated from pulmonary tissue that enhances the biophysical activity of surfactant phospholipids. Like surfactant phospholipid, SP-C is produced by epithelial cells in the distal respiratory epithelium, and its expression increases during the latter part of gestation. A chimeric gene containing 3.6 kilobases of the promoter and 5{prime}-flanking sequences of the human SP-C gene was used to express diphtheria toxin A. The SP-C-diphtheria toxin A fusion gene was injected into fertilized mouse eggs to produce transgenic mice. Affected mice developed respiratory failure in the immediate postnatal period. Morphologic analysis of lungs from affected pups showed variable but severe cellular injury confined to pulmonary tissues. Ultrastructural changes consistent with cell death and injury were prominent in the distal respiratory epithelium. Proximal components of the tracheobronchial tree were not severely affected. Transgenic animals were of normal size at birth, and structural abnormalities were not detected in nonpulmonary tissues. Lung-specific diphtheria toxin A expression controlled by the human SP-C gene injured type II epithelial cells and caused extensive necrosis of the distal respiratory epithelium. The absence of type I epithelial cells in the most severely affected transgenic animals supports the concept that developing type II cells serve as precursors to type I epithelial cells.

  7. Glucose transporter expression in human skeletal muscle fibers

    DEFF Research Database (Denmark)

    Gaster, M; Handberg, A; Beck-Nielsen, H

    2000-01-01

    , but its expression is markedly reduced around birth and is further reduced to undetectable levels within the first year of life; 2) GLUT-3 protein expression appears at 18 wk of gestation and disappears after birth; and 3) GLUT-4 protein is diffusely expressed in muscle cells throughout gestation, whereas...... after birth, the characteristic subcellular localization is as seen in adult muscle fibers. Our results show that GLUT-1, GLUT-3, and GLUT-4 seem to be of importance during muscle fiber growth and development. GLUT-5 protein was undetectable in fetal and adult skeletal muscle fibers. In adult muscle...... amplification (TSA) technique to detect the localization of glucose transporter expression in human skeletal muscle. We found expression of GLUT-1, GLUT-3, and GLUT-4 in developing human muscle fibers showing a distinct expression pattern. 1) GLUT-1 is expressed in human skeletal muscle cells during gestation...

  8. HJURP regulates cellular senescence in human fibroblasts and endothelial cells via a p53-dependent pathway.

    Science.gov (United States)

    Heo, Jong-Ik; Cho, Jung Hee; Kim, Jae-Ryong

    2013-08-01

    Holliday junction recognition protein (HJURP), a centromere protein-A (CENP-A) histone chaperone, mediates centromere-specific assembly of CENP-A nucleosome, contributing to high-fidelity chromosome segregation during cell division. However, the role of HJURP in cellular senescence of human primary cells remains unclear. We found that the expression levels of HJURP decreased in human dermal fibroblasts and umbilical vein endothelial cells in replicative or premature senescence. Ectopic expression of HJURP in senescent cells partially overcame cell senescence. Conversely, downregulation of HJURP in young cells led to premature senescence. p53 knockdown, but not p16 knockdown, abolished senescence phenotypes caused by HJURP reduction. These data suggest that HJURP plays an important role in the regulation of cellular senescence through a p53-dependent pathway and might contribute to tissue or organismal aging and protection of cellular transformation.

  9. Human Empathy, Personality and Experience Affect the Emotion Ratings of Dog and Human Facial Expressions

    Science.gov (United States)

    Kujala, Miiamaaria V.; Somppi, Sanni; Jokela, Markus; Vainio, Outi; Parkkonen, Lauri

    2017-01-01

    Facial expressions are important for humans in communicating emotions to the conspecifics and enhancing interpersonal understanding. Many muscles producing facial expressions in humans are also found in domestic dogs, but little is known about how humans perceive dog facial expressions, and which psychological factors influence people’s perceptions. Here, we asked 34 observers to rate the valence, arousal, and the six basic emotions (happiness, sadness, surprise, disgust, fear, and anger/aggressiveness) from images of human and dog faces with Pleasant, Neutral and Threatening expressions. We investigated how the subjects’ personality (the Big Five Inventory), empathy (Interpersonal Reactivity Index) and experience of dog behavior affect the ratings of dog and human faces. Ratings of both species followed similar general patterns: human subjects classified dog facial expressions from pleasant to threatening very similarly to human facial expressions. Subjects with higher emotional empathy evaluated Threatening faces of both species as more negative in valence and higher in anger/aggressiveness. More empathetic subjects also rated the happiness of Pleasant humans but not dogs higher, and they were quicker in their valence judgments of Pleasant human, Threatening human and Threatening dog faces. Experience with dogs correlated positively with ratings of Pleasant and Neutral dog faces. Personality also had a minor effect on the ratings of Pleasant and Neutral faces in both species. The results imply that humans perceive human and dog facial expression in a similar manner, and the perception of both species is influenced by psychological factors of the evaluators. Especially empathy affects both the speed and intensity of rating dogs’ emotional facial expressions. PMID:28114335

  10. Human Empathy, Personality and Experience Affect the Emotion Ratings of Dog and Human Facial Expressions.

    Directory of Open Access Journals (Sweden)

    Miiamaaria V Kujala

    Full Text Available Facial expressions are important for humans in communicating emotions to the conspecifics and enhancing interpersonal understanding. Many muscles producing facial expressions in humans are also found in domestic dogs, but little is known about how humans perceive dog facial expressions, and which psychological factors influence people's perceptions. Here, we asked 34 observers to rate the valence, arousal, and the six basic emotions (happiness, sadness, surprise, disgust, fear, and anger/aggressiveness from images of human and dog faces with Pleasant, Neutral and Threatening expressions. We investigated how the subjects' personality (the Big Five Inventory, empathy (Interpersonal Reactivity Index and experience of dog behavior affect the ratings of dog and human faces. Ratings of both species followed similar general patterns: human subjects classified dog facial expressions from pleasant to threatening very similarly to human facial expressions. Subjects with higher emotional empathy evaluated Threatening faces of both species as more negative in valence and higher in anger/aggressiveness. More empathetic subjects also rated the happiness of Pleasant humans but not dogs higher, and they were quicker in their valence judgments of Pleasant human, Threatening human and Threatening dog faces. Experience with dogs correlated positively with ratings of Pleasant and Neutral dog faces. Personality also had a minor effect on the ratings of Pleasant and Neutral faces in both species. The results imply that humans perceive human and dog facial expression in a similar manner, and the perception of both species is influenced by psychological factors of the evaluators. Especially empathy affects both the speed and intensity of rating dogs' emotional facial expressions.

  11. The Effect of Future Ambient Air Pollution on Human Premature Mortality to 2100 Using Output from the ACCMIP Model Ensemble

    Science.gov (United States)

    Silva, Raquel A.; West, J. Jason; Lamarque, Jean-Francois; Shindell, Drew T.; Collins, William J.; Dalsoren, Stig; Faluvegi, Greg; Folberth, Gerd; Horowitz, Larry W.; Nagashima, Tatsuya; hide

    2016-01-01

    Ambient air pollution from ground-level ozone and fine particulate matter (PM(sub 2.5)) is associated with premature mortality. Future concentrations of these air pollutants will be driven by natural and anthropogenic emissions and by climate change. Using anthropogenic and biomass burning emissions projected in the four Representative Concentration Pathway scenarios (RCPs), the ACCMIP ensemble of chemistry climate models simulated future concentrations of ozone and PM(sub 2.5) at selected decades between 2000 and 2100. We use output from the ACCMIP ensemble, together with projections of future population and baseline mortality rates, to quantify the human premature mortality impacts of future ambient air pollution. Future air-pollution-related premature mortality in 2030, 2050 and 2100 is estimated for each scenario and for each model using a health impact function based on changes in concentrations of ozone and PM(sub 2.5) relative to 2000 and projected future population and baseline mortality rates. Additionally, the global mortality burden of ozone and PM(sub 2.5) in 2000 and each future period is estimated relative to 1850 concentrations, using present-day and future population and baseline mortality rates. The change in future ozone concentrations relative to 2000 is associated with excess global premature mortality in some scenarios/periods, particularly in RCP8.5 in 2100 (316 thousand deaths per year), likely driven by the large increase in methane emissions and by the net effect of climate change projected in this scenario, but it leads to considerable avoided premature mortality for the three other RCPs. However, the global mortality burden of ozone markedly increases from 382000 (121000 to 728000) deaths per year in 2000 to between 1.09 and 2.36 million deaths per year in 2100, across RCPs, mostly due to the effect of increases in population and baseline mortality rates. PM(sub 2.5) concentrations decrease relative to 2000 in all scenarios, due to

  12. The effect of future ambient air pollution on human premature mortality to 2100 using output from the ACCMIP model ensemble

    Directory of Open Access Journals (Sweden)

    R. A. Silva

    2016-08-01

    Full Text Available Ambient air pollution from ground-level ozone and fine particulate matter (PM2.5 is associated with premature mortality. Future concentrations of these air pollutants will be driven by natural and anthropogenic emissions and by climate change. Using anthropogenic and biomass burning emissions projected in the four Representative Concentration Pathway scenarios (RCPs, the ACCMIP ensemble of chemistry–climate models simulated future concentrations of ozone and PM2.5 at selected decades between 2000 and 2100. We use output from the ACCMIP ensemble, together with projections of future population and baseline mortality rates, to quantify the human premature mortality impacts of future ambient air pollution. Future air-pollution-related premature mortality in 2030, 2050 and 2100 is estimated for each scenario and for each model using a health impact function based on changes in concentrations of ozone and PM2.5 relative to 2000 and projected future population and baseline mortality rates. Additionally, the global mortality burden of ozone and PM2.5 in 2000 and each future period is estimated relative to 1850 concentrations, using present-day and future population and baseline mortality rates. The change in future ozone concentrations relative to 2000 is associated with excess global premature mortality in some scenarios/periods, particularly in RCP8.5 in 2100 (316 thousand deaths year−1, likely driven by the large increase in methane emissions and by the net effect of climate change projected in this scenario, but it leads to considerable avoided premature mortality for the three other RCPs. However, the global mortality burden of ozone markedly increases from 382 000 (121 000 to 728 000 deaths year−1 in 2000 to between 1.09 and 2.36 million deaths year−1 in 2100, across RCPs, mostly due to the effect of increases in population and baseline mortality rates. PM2.5 concentrations decrease relative to 2000 in all scenarios

  13. Characterization of human septic sera induced gene expression modulation in human myocytes

    Science.gov (United States)

    Hussein, Shaimaa; Michael, Paul; Brabant, Danielle; Omri, Abdelwahab; Narain, Ravin; Passi, Kalpdrum; Ramana, Chilakamarti V.; Parrillo, Joseph E.; Kumar, Anand; Parissenti, Amadeo; Kumar, Aseem

    2009-01-01

    To gain a better understanding of the gene expression changes that occurs during sepsis, we have performed a cDNA microarray study utilizing a tissue culture model that mimics human sepsis. This study utilized an in vitro model of cultured human fetal cardiac myocytes treated with 10% sera from septic patients or 10% sera from healthy volunteers. A 1700 cDNA expression microarray was used to compare the transcription profile from human cardiac myocytes treated with septic sera vs normal sera. Septic sera treatment of myocytes resulted in the down-regulation of 178 genes and the up-regulation of 4 genes. Our data indicate that septic sera induced cell cycle, metabolic, transcription factor and apoptotic gene expression changes in human myocytes. Identification and characterization of gene expression changes that occur during sepsis may lead to the development of novel therapeutics and diagnostics. PMID:19684886

  14. Premature infants' health at multiple induced pregnancy.

    Directory of Open Access Journals (Sweden)

    Chernenkov Yu.V.

    2015-09-01

    Full Text Available Objective: to define the risk factors adversely influencing prenatal development at premature birth at use of methods of assisted reproductive technology (ART; to estimate premature' infants health from multiple induced pregnancy according to Perinatal Center of Saratov for last 3 years. Material and Methods. Under supervision there were 139 pregnant women with application ART. 202 children (51 twins were born and 5 triplet babies, from them 83 premature infants born from multiple induced pregnancy have been analyzed. Results. The newborns examined by method ART, were distributed as follows: 22-28 weeks — 19 children; 29-32 weeks — 23; 33-36 weeks — 41. Asphyxia at birth was marked at all premature infants. Respiratory insufficiency at birth is revealed in 87,3% of cases. The most frequent pathologies in premature infants are revealed: neurologic infringements and bronchopulmonary pathology occured at all children, developmental anomaly — 33, 8%, retinopathies in premature infants — 26,5%. The mortality causes include: extreme immaturity, cerebral leukomalacia, IVN 3 degrees. Conclusion. The risk factors, premature birth at application of methods ART are revealed: aged primiparas, pharmacological influence, absence of physiological conditions of prenatal development; multifetation. The high percent of birth of children with ELBW and ULBW is revealed. RDCN with further BPD development, retinopathies in premature infants and CNS defeat is more often occured.

  15. 7 CFR 29.1050 - Prematurity.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Prematurity. 29.1050 Section 29.1050 Agriculture Regulations of the Department of Agriculture AGRICULTURAL MARKETING SERVICE (Standards, Inspections, Marketing... Type 92) § 29.1050 Prematurity. A condition of growth and development characteristic of the lower...

  16. xidative Stress and Retinopathy of Prematurity

    OpenAIRE

    Ümeyye Taka Aydın; Hatip Aydın; Osman Çekiç

    2014-01-01

    Oxidative stress plays an important role in the etiology of retinopathy of prematurity. Insufficient antioxidant system and increased oxidative stress in premature infants lead to the development of the disease. Understanding the mechanism of oxidative stress and antioxidant system and the related signaling pathways contribute to the development of novel options for diagnosis and treatment of retinopathy of prematurity. The current review aimed to evaluate the relationship between ox...

  17. Educational paper: Retinopathy of prematurity.

    Science.gov (United States)

    Casteels, Ingele; Cassiman, Catherine; Van Calster, Joachim; Allegaert, Karel

    2012-06-01

    Retinopathy of prematurity (ROP) is a proliferative retinal vascular disease affecting the premature infant with an incompletely vascularized retina. The spectrum of ophthalmological findings in ROP exists from minimal sequelae, which do not affect vision, to bilateral retinal detachment and total blindness. With the increased survival of very small infants, retinopathy of prematurity has become one of the leading causes of childhood blindness. Over the past two decades, major advances have been made in understanding the pathogenesis of ROP, to a large extent as a result of changes in clinical risk factors (oxygen and non-oxygen related) and characteristics observed in ROP cases. This article provides a literature review on the evolution in clinical characteristics, classification and treatment modalities and indications of ROP. Special attention is hereby paid to the neonatal factors influencing the development of ROP and to the necessity for everyone caring for premature babies to have a well-defined screening and treatment protocol for ROP. Such screening protocol needs to be based on a unit-specific ROP risk profile and, consequently, may vary between different European regions. Retinopathy of prematurity is an important cause of ocular morbidity and blindness in children. With better understanding of the pathogenesis, screening and treatment guidelines have changed over time and are unit specific.

  18. Quality of human milk expressed in a human milk bank and at home.

    Science.gov (United States)

    Borges, Mayla S; Oliveira, Angela M de M; Hattori, Wallisen T; Abdallah, Vânia O S

    2017-08-30

    To evaluate the quality of the human milk expressed at home and at a human milk bank. This a retrospective, analytical, and observational study, performed by assessing titratable acidity records and the microbiological culture of 100 human milk samples expressed at home and at a human milk bank, in 2014. For the statistical analysis, generalized estimating equations (GEE) and the chi-squared test were used. When comparing the two sample groups, no significant difference was found, with 98% and 94% of the samples being approved among those collected at the milk bank and at home, respectively. No main interaction effect between local and titratable acidity records (p=0.285) was observed, and there was no statistically significant difference between the expected and observed values for the association between the collection place and the microbiological culture results (p=0.307). The quality of human milk expressed at home and at the milk bank are in agreement with the recommended standards, confirming that the expression of human milk at home is as safe as expression at the human milk bank, provided that the established hygiene, conservation, storage, and transport standards are followed. Copyright © 2017 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

  19. Refractive status and optical components of premature babies with or without retinopathy of prematurity at 3-4 years old.

    Science.gov (United States)

    Ouyang, Li-Juan; Yin, Zheng-Qin; Ke, Ning; Chen, Xin-Ke; Liu, Qin; Fang, Jing; Chen, Lin; Chen, Xiu-Rong; Shi, Hui; Tang, Ling; Pi, Lian-Hong

    2015-01-01

    To investigate the refractive status and optical components of premature babies with or without retinopathy of prematurity (ROP) at 3-4 years old, and to explore the influence of prematurity and ROP on the refractive status and optical components. Premature babies receiving fundus examination were recruited into ROP group and non-ROP group, with age-matched full-term babies as controls. The incidence of myopia was the highest in ROP (3/59, 5.08%). The incidence of astigmatism was significantly different between ROP (37.29%, 22/59) and controls (17.86%, 15/84). The corneal refractive power in ROP and non-ROP was more potent compared with controls (PPremature babies with or without ROP are susceptible to myopia and astigmatism. ROP, prematurity and low birth-weight synergistically influence the development of refractive status and optical components, of which the prematurity and low birth-weight are more important.

  20. Autoimmune premature ovarian failure

    Directory of Open Access Journals (Sweden)

    Beata Komorowska

    2017-02-01

    Full Text Available Premature ovarian failure (POF, also termed as primary ovarian insufficiency (POI, is a highly heterogenous condition affecting 0.5-3.0% of women in childbearing age. These young women comprise quite a formidable group with unique physical and psychological needs that require special attention. Premature ovarian senescence (POS in all of its forms evolves insidiously as a basically asymptomatic process, leading to complete loss of ovarian function, and POI/POF diagnoses are currently made at relatively late stages. Well-known and well-documented risk factors exist, and the presence or suspicion of autoimmune disorder should be regarded as an important one. Premature ovarian failure is to some degree predictable in its occurrence and should be considered while encountering young women with loss of menstrual regularity, especially when there is a concomitant dysfunction in the immune system.

  1. High-risk human papillomavirus infection is associated with premature rupture of membranes.

    Science.gov (United States)

    Cho, GeumJoon; Min, Kyung-Jin; Hong, Hye-Ri; Kim, SuhngWook; Hong, Jin-Hwa; Lee, Jae-Kwan; Oh, Min-Jeong; Kim, HaiJoong

    2013-09-06

    Human papillomavirus (HPV) is known to be more prevalent in spontaneous abortions than in elective terminations of pregnancy. More recently, placental infection with HPV was shown to be associated with spontaneous preterm delivery. However, no study has evaluated the prevalence of HPV infection in pregnant Korean females and its association with adverse pregnancy outcomes. We conducted a cross-sectional study of 311 females who gave birth at Korea University Medical Center. Our sample included 45 preterm deliveries, 50 cases of premature rupture of the membranes (PROM), 21 preeclampsia cases, and 8 gestational diabetes mellitus (GDM) patients. We used the Hybrid Capture II system to detect high-risk (HR)-HPV infection at six weeks postpartum. The prevalence of HR-HPV infection was 14.1%. Women with HR-HPV infection had a higher incidence of PROM than those without HR-HPV. HR-HPV infection was associated with an increased risk of PROM (OR, 2.380; 95% CI, 1.103-5.134). The prevalence of preterm delivery, preeclampsia, or GDM was not different between the two groups. We observed a high prevalence of HR-HPV infection in pregnant women. Moreover, HR-HPV infection was associated with a risk of PROM at term. Further studies are needed to evaluate mechanisms by which HR-HPV infection induces PROM.

  2. Premature infant

    Science.gov (United States)

    ... matter Infection or neonatal sepsis Low blood sugar (hypoglycemia) Neonatal respiratory distress syndrome, extra air in the tissue ... Outlook (Prognosis) Prematurity used to be a major cause of infant deaths. Improved medical and nursing techniques ...

  3. Reevaluation of the DHA requirement for the premature infant.

    Science.gov (United States)

    Lapillonne, Alexandre; Jensen, Craig L

    2009-01-01

    The long-chain polyunsaturated fatty acid (LC-PUFA) intake in preterm infants is crucial for normal central nervous system development and has the potential for long-lasting effects that extend beyond the period of dietary insufficiency. While much attention has focused on improving their nutritional intake, many premature infants do not receive an adequate DHA supply. We demonstrate that enterally fed premature infants exhibit daily DHA deficit of 20mg/kg.d, representing 44% of the DHA that should have been accumulated. Furthermore, the DHA content of human milk and current preterm formulas cannot compensate for an early DHA deficit which may occur during the first month of life. We recommend breast-feeding, which supplies preformed LC-PUFA, as the preferred method of feeding for preterm infants. However, to fulfill the specific DHA requirement of these infants, we recommend increasing the DHA content of human milk either by providing the mothers with a DHA supplement or by adding DHA directly to the milk. Increasing the DHA content above 1% total fatty acids appears to be safe and may enhance neurological development particularly that of infants with a birth weight below 1250 g. We estimate that human milk and preterm formula should contain approximately 1.5% of fatty acid as DHA to prevent the appearance of a DHA deficit and to compensate for the early DHA deficit.

  4. Altered Amygdala Development and Fear Processing in Prematurely Born Infants

    Science.gov (United States)

    Cismaru, Anca Liliana; Gui, Laura; Vasung, Lana; Lejeune, Fleur; Barisnikov, Koviljka; Truttmann, Anita; Borradori Tolsa, Cristina; Hüppi, Petra S.

    2016-01-01

    Context: Prematurely born children have a high risk of developmental and behavioral disabilities. Cerebral abnormalities at term age have been clearly linked with later behavior alterations, but existing studies did not focus on the amygdala. Moreover, studies of early amygdala development after premature birth in humans are scarce. Objective: To compare amygdala volumes in very preterm infants at term equivalent age (TEA) and term born infants, and to relate premature infants’ amygdala volumes with their performance on the Laboratory Temperament Assessment Battery (Lab-TAB) fear episode at 12 months. Participants: Eighty one infants born between 2008 and 2014 at the University Hospitals of Geneva and Lausanne, taking part in longitudinal and functional imaging studies, who had undergone a magnetic resonance imaging (MRI) scan at TEA enabling manual amygdala delineation. Outcomes: Amygdala volumes assessed by manual segmentation of MRI scans; volumes of cortical and subcortical gray matter, white matter and cerebrospinal fluid (CSF) automatically segmented in 66 infants; scores for the Lab-TAB fear episode for 42 premature infants at 12 months. Results: Amygdala volumes were smaller in preterm infants at TEA than term infants (mean difference 138.03 mm3, p amygdala volumes were larger than left amygdala volumes (mean difference 36.88 mm3, p Amygdala volumes showed significant correlation with the intensity of the escape response to a fearsome toy (rs = 0.38, p = 0.013), and were larger in infants showing an escape response compared to the infants showing no escape response (mean difference 120.97 mm3, p = 0.005). Amygdala volumes were not significantly correlated with the intensity of facial fear, distress vocalizations, bodily fear and positive motor activity in the fear episode. Conclusion: Our results indicate that premature birth is associated with a reduction in amygdala volumes and white matter volumes at TEA, suggesting that altered amygdala development

  5. Genetic effects on gene expression across human tissues

    NARCIS (Netherlands)

    Battle, Alexis; Brown, Christopher D.; Engelhardt, Barbara E.; Montgomery, Stephen B.; Aguet, François; Ardlie, Kristin G.; Cummings, Beryl B.; Gelfand, Ellen T.; Getz, Gad; Hadley, Kane; Handsaker, Robert E.; Huang, Katherine H.; Kashin, Seva; Karczewski, Konrad J.; Lek, Monkol; Li, Xiao; MacArthur, Daniel G.; Nedzel, Jared L.; Nguyen, Duyen T.; Noble, Michael S.; Segrè, Ayellet V.; Trowbridge, Casandra A.; Tukiainen, Taru; Abell, Nathan S.; Balliu, Brunilda; Barshir, Ruth; Basha, Omer; Bogu, Gireesh K.; Brown, Andrew; Castel, Stephane E.; Chen, Lin S.; Chiang, Colby; Conrad, Donald F.; Cox, Nancy J.; Damani, Farhan N.; Davis, Joe R.; Delaneau, Olivier; Dermitzakis, Emmanouil T.; Eskin, Eleazar; Ferreira, Pedro G.; Frésard, Laure; Gamazon, Eric R.; Garrido-Martín, Diego; Gewirtz, Ariel D. H.; Gliner, Genna; Gloudemans, Michael J.; Guigo, Roderic; Hall, Ira M.; Han, Buhm; He, Yuan

    2017-01-01

    Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression

  6. Human Alpha Defensin 5 Expression in the Human Kidney and Urinary Tract

    Science.gov (United States)

    Porter, Edith; Bevins, Charles L.; DiRosario, Julianne; Becknell, Brian; Wang, Huanyu

    2012-01-01

    Background The mechanisms that maintain sterility in the urinary tract are incompletely understood. Recent studies have implicated the importance of antimicrobial peptides (AMP) in protecting the urinary tract from infection. Here, we characterize the expression and relevance of the AMP human alpha-defensin 5 (HD5) in the human kidney and urinary tract in normal and infected subjects. Methodology/Principal Findings Using RNA isolated from human kidney, ureter, and bladder tissue, we performed quantitative real-time PCR to show that DEFA5, the gene encoding HD5, is constitutively expressed throughout the urinary tract. With pyelonephritis, DEFA5 expression significantly increased in the kidney. Using immunoblot analysis, HD5 production also increased with pyelonephritis. Immunostaining localized HD5 to the urothelium of the bladder and ureter. In the kidney, HD5 was primarily produced in the distal nephron and collecting tubules. Using immunoblot and ELISA assays, HD5 was not routinely detected in non-infected human urine samples while mean urinary HD5 production increased with E.coli urinary tract infection. Conclusions/Significance DEFA5 is expressed throughout the urinary tract in non-infected subjects. Specifically, HD5 is expressed throughout the urothelium of the lower urinary tract and in the collecting tubules of the kidney. With infection, HD5 expression increases in the kidney and levels become detectable in the urine. To our knowledge, our findings represent the first to quantitate HD5 expression and production in the human kidney. Moreover, this is the first report to detect the presence of HD5 in infected urine samples. Our results suggest that HD5 may have an important role in maintaining urinary tract sterility. PMID:22359618

  7. Prematurity Affects Age of Presentation of Pyloric Stenosis.

    Science.gov (United States)

    Costanzo, Caitlyn M; Vinocur, Charles; Berman, Loren

    2017-02-01

    Term infants with hypertrophic pyloric stenosis (HPS) typically present between 4 and 6 weeks. There is limited consensus, however, regarding age of presentation of premature infants. We aim to determine if there is an association between the degree of prematurity and chronological age of presentation of HPS. A total of 2988 infants who had undergone a pyloromyotomy for HPS were identified from the 2012 and 2013 NSQIP-P Participant Use Files. Two hundred seventeen infants (7.3%) were born prematurely. A greater degree of prematurity was associated with an older chronological age of presentation ( P Prematurity was significantly associated with an increase in overall postoperative morbidity, reintubation, readmission, and postoperative length of stay. When clinicians evaluate an infant with nonbilious emesis with a history of prematurity, they should consider pyloric stenosis if the calculated postconceptional age is between 44 and 50 weeks. When counseling families of premature infants, surgeons should discuss the increased incidence of postpyloromyotomy morbidity.

  8. Expression and function of human hemokinin-1 in human and guinea pig airways.

    Science.gov (United States)

    Grassin-Delyle, Stanislas; Naline, Emmanuel; Buenestado, Amparo; Risse, Paul-André; Sage, Edouard; Advenier, Charles; Devillier, Philippe

    2010-10-07

    Human hemokinin-1 (hHK-1) and endokinins are peptides of the tachykinin family encoded by the TAC4 gene. TAC4 and hHK-1 expression as well as effects of hHK-1 in the lung and airways remain however unknown and were explored in this study. RT-PCR analysis was performed on human bronchi to assess expression of tachykinin and tachykinin receptors genes. Enzyme immunoassay was used to quantify hHK-1, and effects of hHK-1 and endokinins on contraction of human and guinea pig airways were then evaluated, as well as the role of hHK-1 on cytokines production by human lung parenchyma or bronchi explants and by lung macrophages. In human bronchi, expression of the genes that encode for hHK-1, tachykinin NK1-and NK2-receptors was demonstrated. hHK-1 protein was found in supernatants from explants of human bronchi, lung parenchyma and lung macrophages. Exogenous hHK-1 caused a contractile response in human bronchi mainly through the activation of NK2-receptors, which blockade unmasked a NK1-receptor involvement, subject to a rapid desensitization. In the guinea pig trachea, hHK-1 caused a concentration-dependant contraction mainly mediated through the activation of NK1-receptors. Endokinin A/B exerted similar effects to hHK-1 on both human bronchi and guinea pig trachea, whereas endokinins C and D were inactive. hHK-1 had no impact on the production of cytokines by explants of human bronchi or lung parenchyma, or by human lung macrophages. We demonstrate endogenous expression of TAC4 in human bronchi, the encoded peptide hHK-1 being expressed and involved in contraction of human and guinea pig airways.

  9. Expression and function of human hemokinin-1 in human and guinea pig airways

    Directory of Open Access Journals (Sweden)

    Sage Edouard

    2010-10-01

    Full Text Available Abstract Background Human hemokinin-1 (hHK-1 and endokinins are peptides of the tachykinin family encoded by the TAC4 gene. TAC4 and hHK-1 expression as well as effects of hHK-1 in the lung and airways remain however unknown and were explored in this study. Methods RT-PCR analysis was performed on human bronchi to assess expression of tachykinin and tachykinin receptors genes. Enzyme immunoassay was used to quantify hHK-1, and effects of hHK-1 and endokinins on contraction of human and guinea pig airways were then evaluated, as well as the role of hHK-1 on cytokines production by human lung parenchyma or bronchi explants and by lung macrophages. Results In human bronchi, expression of the genes that encode for hHK-1, tachykinin NK1-and NK2-receptors was demonstrated. hHK-1 protein was found in supernatants from explants of human bronchi, lung parenchyma and lung macrophages. Exogenous hHK-1 caused a contractile response in human bronchi mainly through the activation of NK2-receptors, which blockade unmasked a NK1-receptor involvement, subject to a rapid desensitization. In the guinea pig trachea, hHK-1 caused a concentration-dependant contraction mainly mediated through the activation of NK1-receptors. Endokinin A/B exerted similar effects to hHK-1 on both human bronchi and guinea pig trachea, whereas endokinins C and D were inactive. hHK-1 had no impact on the production of cytokines by explants of human bronchi or lung parenchyma, or by human lung macrophages. Conclusions We demonstrate endogenous expression of TAC4 in human bronchi, the encoded peptide hHK-1 being expressed and involved in contraction of human and guinea pig airways.

  10. Prematurity, atopy, and childhood asthma in Puerto Ricans.

    Science.gov (United States)

    Rosas-Salazar, Christian; Ramratnam, Sima K; Brehm, John M; Han, Yueh-Ying; Boutaoui, Nadia; Forno, Erick; Acosta-Pérez, Edna; Alvarez, María; Colón-Semidey, Angel; Canino, Glorisa; Celedón, Juan C

    2014-02-01

    Puerto Rican children share a disproportionate burden of prematurity and asthma in the United States. Little is known about prematurity and childhood asthma in Puerto Rican subjects. We sought to examine whether prematurity is associated with asthma in Puerto Rican children. We performed a case-control study of 678 children aged 6 to 14 years with (n = 351) and without (n = 327) asthma living in San Juan, Puerto Rico. Prematurity was defined by parental report for our primary analysis. In a secondary analysis, we only included children whose parents reported prematurity that required admission to the neonatal intensive care unit. Asthma was defined as physician-diagnosed asthma and wheeze in the prior year. We used logistic regression for analysis. All multivariate models were adjusted for age, sex, household income, atopy (≥1 positive IgE level to common allergens), maternal history of asthma, and early-life exposure to environmental tobacco smoke. In a multivariate analysis there was a significant interaction between prematurity and atopy on asthma (P = .006). In an analysis stratified by atopy, prematurity was associated with a nearly 5-fold increased odds of asthma in atopic children (adjusted odds ratio, 4.7; 95% CI, 1.5-14.3; P = .007). In contrast, there was no significant association between prematurity and asthma in nonatopic children. Similar results were obtained in our analysis of prematurity requiring admission to the neonatal intensive care unit and asthma. Our results suggest that atopy modifies the estimated effect of prematurity on asthma in Puerto Rican children. Prematurity might explain, in part, the high prevalence of atopic asthma in this ethnic group. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  11. Stress-induced premature senescence (SIPS)--influence of SIPS on radiotherapy.

    Science.gov (United States)

    Suzuki, Masatoshi; Boothman, David A

    2008-03-01

    Replicative senescence is a fundamental feature in normal human diploid cells and results from dysfunctional telomeres at the Hayflick cell division limit. Ionizing radiation (IR) prematurely induces the same phenotypes as replicative senescence prior to the Hayflick limit. This process is known as stress-induced premature senescence (SIPS). Since the cell cycle is irreversibly arrested in SIPS-induced cells, even if they are stimulated by various growth factors, it is thought that SIPS is a form of cell death, irreversibly eliminating replicating cells. IR-induced-focus formation of DNA repair proteins, a marker of DNA damage, is detected in SIPS as well as replicative senescent cells. Furthermore, both processes persistently induce cell cycle checkpoint mechanisms, indicating DNA damage created by ionizing radiation induces SIPS in normal cells, possibly by the same mechanisms as those occurring in replicative senescence. Interestingly, IR induces SIPS not only in normal cells, but also in tumor cells. Due to the expression of telomerase in tumor cells, telomere-dependent replicative senescence does not occur. However, SIPS is induced under certain conditions after IR exposure. Thus, cell death triggered by IR can be attributed to apoptosis or SIPS in tumor cells. However, metabolic function remains intact in SIPS-induced cancer cells, and recent studies show that senescence eliminate cells undergoing SIPS secrete various kinds of factors outside the cell, changing the microenvironment. Evidence using co-culture systems containing normal senescent stromal cells and epithelial tumor cells show that factors secreted from senescent stroma cells promote the growth of tumor epithelial cells both in vitro and in vivo. Thus, regulation of factors secreted from SIPS-induced stromal cells, as well as tumor cells, may affect radiotherapy.

  12. Stress-induced premature senescence (SIPS). Influence of SIPS on radiotherapy

    International Nuclear Information System (INIS)

    Suzuki, Masatoshi; Boothman, D.A.

    2008-01-01

    Replicative senescence is a fundamental feature in normal human diploid cells and results from dysfunctional telomeres at the Hayflick cell division limit. Ionizing radiation (IR) prematurely induces the same phenotypes as replicative senescence prior to the Hayflick limit. This process is known as stress-induced premature senescence (SIPS). Since the cell cycle is irreversibly arrested in SIPS-induced cells, even if they are stimulated by various growth factors, it is thought that SIPS is a form of cell death, irreversibly eliminating replicating cells. IR-induced-focus formation of DNA repair proteins, a marker of DNA damage, is detected in SIPS as well as replicative senescent cells. Furthermore, both processes persistently induce cell cycle checkpoint mechanisms, indicating DNA damage created by ionizing radiation induces SIPS in normal cells, possibly by the same mechanisms as those occurring in replicative senescence. Interestingly, IR induces SIPS not only in normal cells, but also in tumor cells. Due to the expression of telomerase in tumor cells, telomere-dependent replicative senescence does not occur. However, SIPS is induced under certain conditions after IR exposure. Thus, cell death triggered by IR can be attributed to apoptosis or SIPS in tumor cells. However, metabolic function remains intact in SIPS-induced cancer cells, and recent studies show that senescence eliminate cells undergoing SIPS secrete various kinds of factors outside the cell, changing the microenvironment. Evidence using co-culture systems containing normal senescent stromal cells and epithelial tumor cells show that factors secreted from senescent stroma cells promote the growth of tumor epithelial cells both in vitro and in vivo. Thus, regulation of factors secreted from SIPS-induced stromal cells, as well as tumor cells, may affect radiotherapy. (author)

  13. Cyclooxygenase-2 expression in the normal human eye and its expression pattern in selected eye tumours

    DEFF Research Database (Denmark)

    Wang, Jinmei; Wu, Yazhen; Heegaard, Steffen

    2011-01-01

    Purpose: Cyclooxygenase-2 (COX-2) is an enzyme involved in neoplastic processes. The purpose of the present study is to investigate COX-2 expression in the normal human eye and the expression pattern in selected eye tumours involving COX-2 expressing cells. Methods: Immunohistochemical staining...... using antibodies against COX-2 was performed on paraffin sections of normal human eyes and selected eye tumours arising from cells expressing COX-2. Results: Cyclooxygenase-2 expression was found in various structures of the normal eye. Abundant expression was seen in the cornea, iris, ciliary body...... and retina. The COX-2 expression was less in tumours deriving from the ciliary epithelium and also in retinoblastoma. Conclusion: Cyclooxygenase-2 is constitutively expressed in normal human eyes. The expression of COX-2 is much lower in selected eye tumours involving COX-2 expressing cells....

  14. Induction of premature chromosome condensation by calyculin A for bio dosimetry

    International Nuclear Information System (INIS)

    Hosseini, S.; Mozdarani, H.

    2004-01-01

    Background: Premature chromosome condensation is a method for interphase chromosome analysis in bio dosimetry. This study was performed to verify the usefulness of premature chromosome condensation induced by calyculin A in human peripheral blood lymphocytes for biological dosimetry and possible construction of dose-response curve. Materials and methods: Peripheral blood was obtained from a healthy donor and exposed to various doses(0.25- 4 Gy) of γ-rays. The frequency of simple breaks and dicentrics were scored in G 2/M chromosomes of Giemsa stained cells. Results:Results show that the frequency of simple chromosome breaks appears to increase linearly with dose; while the frequency of dicentrics apparently increases linear-quadratically with the dose. Conclusion: Induction of chromosome condensation by calyculin A is a powerful biodisimetric method, which provides a high number of spreads for analysis. With the use of this method, it is possible to overcome problems related to low mitotic index or cell-cycle alterations in routine metaphase analysis and low fusion rate in conventional Premature chromosome condensation technique

  15. Premature ovarian failure

    Directory of Open Access Journals (Sweden)

    Persani Luca

    2006-04-01

    Full Text Available Abstract Premature ovarian failure (POF is a primary ovarian defect characterized by absent menarche (primary amenorrhea or premature depletion of ovarian follicles before the age of 40 years (secondary amenorrhea. It is a heterogeneous disorder affecting approximately 1% of women e.g. Turner syndrome represent the major cause of primary amenorrhea associated with ovarian dysgenesis. Despite the description of several candidate genes, the cause of POF remains undetermined in the vast majority of the cases. Management includes substitution of the hormone defect by estrogen/progestin preparations. The only solution presently available for the fertility defect in women with absent follicular reserve is ovum donation.

  16. Emotion expression in human punishment behavior.

    Science.gov (United States)

    Xiao, Erte; Houser, Daniel

    2005-05-17

    Evolutionary theory reveals that punishment is effective in promoting cooperation and maintaining social norms. Although it is accepted that emotions are connected to punishment decisions, there remains substantial debate over why humans use costly punishment. Here we show experimentally that constraints on emotion expression can increase the use of costly punishment. We report data from ultimatum games, where a proposer offers a division of a sum of money and a responder decides whether to accept the split, or reject and leave both players with nothing. Compared with the treatment in which expressing emotions directly to proposers is prohibited, rejection of unfair offers is significantly less frequent when responders can convey their feelings to the proposer concurrently with their decisions. These data support the view that costly punishment might itself be used to express negative emotions and suggest that future studies will benefit by recognizing that human demand for emotion expression can have significant behavioral consequences in social environments, including families, courts, companies, and markets.

  17. Conceptualizing pathways linking women's empowerment and prematurity in developing countries.

    Science.gov (United States)

    Afulani, Patience A; Altman, Molly; Musana, Joseph; Sudhinaraset, May

    2017-11-08

    Globally, prematurity is the leading cause of death in children under the age of 5. Many efforts have focused on clinical approaches to improve the survival of premature babies. There is a need, however, to explore psychosocial, sociocultural, economic, and other factors as potential mechanisms to reduce the burden of prematurity. Women's empowerment may be a catalyst for moving the needle in this direction. The goal of this paper is to examine links between women's empowerment and prematurity in developing settings. We propose a conceptual model that shows pathways by which women's empowerment can affect prematurity and review and summarize the literature supporting the relationships we posit. We also suggest future directions for research on women's empowerment and prematurity. The key words we used for empowerment in the search were "empowerment," "women's status," "autonomy," and "decision-making," and for prematurity we used "preterm," "premature," and "prematurity." We did not use date, language, and regional restrictions. The search was done in PubMed, Population Information Online (POPLINE), and Web of Science. We selected intervening factors-factors that could potentially mediate the relationship between empowerment and prematurity-based on reviews of the risk factors and interventions to address prematurity and the determinants of those factors. There is limited evidence supporting a direct link between women's empowerment and prematurity. However, there is evidence linking several dimensions of empowerment to factors known to be associated with prematurity and outcomes for premature babies. Our review of the literature shows that women's empowerment may reduce prematurity by (1) preventing early marriage and promoting family planning, which will delay age at first pregnancy and increase interpregnancy intervals; (2) improving women's nutritional status; (3) reducing domestic violence and other stressors to improve psychological health; and (4) improving

  18. Assessment of hormonal activity in patients with premature ejaculation

    Directory of Open Access Journals (Sweden)

    Lütfi Canat

    Full Text Available ABSTRACT Purpose Premature ejaculation is considered the most common type of male sexual dysfunction. Hormonal controls of ejaculation have not been exactly elucidated. The aim of our study is to investigate the role of hormonal factors in patients with premature ejaculation. Materials and Methods Sixty-three participants who consulted our outpatient clinics with complaints of premature ejaculation and 39 healthy men as a control group selected from volunteers were included in the study. A total of 102 sexual active men aged between 21 and 76 years were included. Premature ejaculation diagnostic tool questionnaires were used to assessment of premature ejaculation. Serum levels of follicle stimulating hormone, luteinizing hormone, prolactin, total and free testosterone, thyroid-stimulating hormone, free triiodothyronine and thyroxine were measured. Results Thyroid-stimulating hormone, luteinizing hormone, and prolactin levels were significantly lower in men with premature ejaculation according to premature ejaculation diagnostic tool (p=0.017, 0.007 and 0.007, respectively. Luteinizing hormone level (OR, 1.293; p=0.014 was found to be an independent risk factor for premature ejaculation. Conclusions Luteinizing hormone, prolactin, and thyroid-stimulating hormone levels are associated with premature ejaculation which was diagnosed by premature ejaculation diagnostic tool questionnaires. The relationship between these findings have to be determined by more extensive studies.

  19. Calculation of organ doses in x-ray examinations of premature babies

    International Nuclear Information System (INIS)

    Smans, Kristien; Tapiovaara, Markku; Cannie, Mieke; Struelens, Lara; Vanhavere, Filip; Smet, Marleen; Bosmans, Hilde

    2008-01-01

    Lung disease represents one of the most life-threatening conditions in prematurely born children. In the evaluation of the neonatal chest, the primary and most important diagnostic study is the chest radiograph. Since prematurely born children are very sensitive to radiation, those radiographs may lead to a significant radiation detriment. Knowledge of the radiation dose is therefore necessary to justify the exposures. To calculate doses in the entire body and in specific organs, computational models of the human anatomy are needed. Using medical imaging techniques, voxel phantoms have been developed to achieve a representation as close as possible to the anatomical properties. In this study two voxel phantoms, representing prematurely born babies, were created from computed tomography- and magnetic resonance images: Phantom 1 (1910 g) and Phantom 2 (590 g). The two voxel phantoms were used in Monte Carlo calculations (MCNPX) to assess organ doses. The results were compared with the commercially available software package PCXMC in which the available mathematical phantoms can be downsized toward the prematurely born baby. The simple phantom-scaling method used in PCXMC seems to be sufficient to calculate doses for organs within the radiation field. However, one should be careful in specifying the irradiation geometry. Doses in organs that are wholly or partially outside the primary radiation field depend critically on the irradiation conditions and the phantom model

  20. Premature Ejaculation

    Science.gov (United States)

    ... include the following: Anxiety about performance Guilty feelings Depression Stress Relationship problems Men who have a low amount of a special ... on your favorite sports team. Psychological assistance Anxiety, depression ... may help men who have premature ejaculation. Some antidepressants seem to ...

  1. Characterization of human septic sera induced gene expression modulation in human myocytes

    OpenAIRE

    Hussein, Shaimaa; Michael, Paul; Brabant, Danielle; Omri, Abdelwahab; Narain, Ravin; Passi, Kalpdrum; Ramana, Chilakamarti V.; Parrillo, Joseph E.; Kumar, Anand; Parissenti, Amadeo; Kumar, Aseem

    2009-01-01

    To gain a better understanding of the gene expression changes that occurs during sepsis, we have performed a cDNA microarray study utilizing a tissue culture model that mimics human sepsis. This study utilized an in vitro model of cultured human fetal cardiac myocytes treated with 10% sera from septic patients or 10% sera from healthy volunteers. A 1700 cDNA expression microarray was used to compare the transcription profile from human cardiac myocytes treated with septic sera vs normal sera....

  2. Acute appendicitis in a premature baby

    International Nuclear Information System (INIS)

    Beluffi, Giampiero; Alberici, Elisa

    2002-01-01

    A case of acute appendicitis in a premature baby in whom diagnosis was suggested on plain films of the abdomen is presented. In this baby air in a hollow viscus suspected of being an enlarged appendix was the clue to diagnosis. The diagnostic dilemma of this rare and life-threatening condition in premature babies and newborns is underlined. The relevance of different imaging modalities and of different findings in this age group is discussed. Awareness of this rare condition and possible differential diagnosis in newborns and premature babies is stressed. (orig.)

  3. Comparative study of visual functions in premature pre-school children with and without retinopathy of prematurity

    Directory of Open Access Journals (Sweden)

    Lígia Beatriz Bonotto

    2014-01-01

    Full Text Available Purpose: Observe whether there are differences in visual functions among premature infants with treated retinopathy of prematurity (ROP in relation to preterm infants with ROP and spontaneous regression; and among these two groups with ROP and the control group without ROP. Methods: Crosssectional observational no blind study. Premature infants were born between 06/199206/2006 and were exam between 06/200912/2010; registered in data of Hospital de Olhos Sandalla Amin Ghanem; with gestational age less than or equal to 32 weeks and 1,599 g born weigh; without ROP and ROP stages II or III, in one of the eyes, with spontaneous regression or with treatment; at least three visits during the selection period at maximum 6 months in the first exam and minimum 4 years of age in reassessment (chronological age were include. Premature that did not respond or were not located for reassessment and those that did not have conditions to do the exams were exclude. Study's groups: G1 ROP posttreatment; G2ROP postspontaneous regression; G3 without ROP (control. Visual function evaluated with visual acuity (VA, contrast sensitivity test (CST, color test (CT, eye movement, stereopsis. Results: Overall, there were 24 premature infants and 48 eyes. Normal VA: 64.28% (G1, 87.5% (G2 and 100% (G3; Normal CST: 66.67% (G1, 100% (G2 and 55.56% (G3; Normal Ishihara CT: 100% (G1 and G2 and 86% (G3; Normal Farnsworth CT: 20% (G1, 75% (G2 and 50% (G3. Normal stereoacuity: 0.00% (G1; 25% (G2 and 3.5% (G3. Strabismus: 37% (G2, 0.00% (G1 and G3. The prevalent tendency for lower response in CST and CT between the premature children in group G3 and Farnsworth color test in G1 is a curious result of this work and more study is necessary about these visual functions in older premature children. Conclusion: The visual functions showed no statistically significant difference among the groups studied.

  4. Expressive language of two year-old pre-term and full-term children.

    Science.gov (United States)

    Isotani, Selma Mie; Azevedo, Marisa Frasson de; Chiari, Brasília Maria; Perissinoto, Jacy

    2009-01-01

    expressive language of pre-term children. to compare the expressive vocabulary of two year-old children born prematurely, to that of those born at term. the study sample was composed by 118 speech-language assessment protocols, divided in two groups: the pre-term group (PTG) composed by 58 underweight premature children followed by a multi-professional team at the Casa do Prematuro (House of Premature Children) at Unifesp, and the full-term group (FTG) composed by 60 full-term born children. In order to evaluate the expressive language of these children, the Lave - Lista de Avaliação do Vocabulário Expressivo (Assessment List of the Expressive Vocabulary) was used. The Lave is an adaptation of the LDS - Language Development Survey - for the Brazilian Portuguese Language. The Lave investigates the expressive language and detects delays in oral language. children born underweight and prematurely present a greater occurrence of expressive language delay, 27.6%. These pre-term children present significantly lower expressive vocabulary and phrasal extension than children of the same age born at full-term in all semantic categories. Family income proved to be positively associated to phrasal extension, as well as to gestational age and weight at birth; thus indicating the effect of these adverse conditions still during the third year of age. The audiological status was associated to word utterances in the PTG. children born prematurely and underweight are at risk in terms of vocabulary development; this determines the need for speech-therapy intervention programs.

  5. Erythropoetin receptor expression in the human diabetic retina

    Directory of Open Access Journals (Sweden)

    Tsang Stephen H

    2009-11-01

    Full Text Available Abstract Background Recent evidence suggests erythropoietin (EPO and the erythropoietin receptor (EPOR may play a direct role in the pathogenesis of diabetic retinopathy. Better characterization of the EPO-EPOR signaling system in the ischemic retina may offer a new therapeutic modality for ischemic ophthalmic diseases. This study was performed to identify EPOR mRNA expression in the human diabetic eye. Findings EPOR antisense RNA probes were validated on human pancreas tissue. In the normal eye, EPOR was expressed in the retinal ganglion cell layer. Minimal expression was observed in the inner and outer nuclear layer. Under conditions of diabetic retinopathy, EPOR expression shifted to photoreceptor cells. Increased expression was also observed in the peripheral retina. Conclusion EPOR expression may be a biomarker or contribute to disease mechanisms in diabetic retinopathy.

  6. A new way of thinking about complications of prematurity.

    Science.gov (United States)

    Moore, Tiffany A; Berger, Ann M; Wilson, Margaret E

    2014-01-01

    The morbidity and mortality of preterm infants are impacted by their ability to maintain physiologic homeostasis using metabolic, endocrine, and immunologic mechanisms independent of the mother's placenta. Exploring McEwen's allostatic load model in preterm infants provides a new way to understand the altered physiologic processes associated with frequently occurring complications of prematurity such as bronchopulmonary dysplasia, intraventricular hemorrhage, necrotizing enterocolitis, and retinopathy of prematurity. The purpose of this article is to present a new model to enhance understanding of the altered physiologic processes associated with complications of prematurity. The model of allostatic load and complications of prematurity was derived to explore the relationship between general stress of prematurity and complications of prematurity. The proposed model uses the concepts of general stress of prematurity, allostasis, physiologic response patterns (adaptive-maladaptive), allostatic load, and complications of prematurity. These concepts are defined and theoretical relationships in the proposed model are interpreted using the four maladaptive response patterns of repeated hits, lack of adaptation, prolonged response, and inadequate response. Empirical evidence for cortisol, inflammation, and oxidative stress responses are used to support the theoretical relationships. The proposed model provides a new way of thinking about physiologic dysregulation in preterm infants. The ability to describe and understand complex physiologic mechanisms involved in complications of prematurity is essential for research. Advancing the knowledge of complications of prematurity will advance clinical practice and research and lead to testing of interventions to reduce negative outcomes in preterm infants.

  7. Genetic and Environmental Influences on Retinopathy of Prematurity

    Science.gov (United States)

    Ortega-Molina, J. M.; Anaya-Alaminos, R.; Uberos-Fernández, J.; Solans-Pérez de Larraya, A.; Chaves-Samaniego, M. J.; Salgado-Miranda, A.; Piñar-Molina, R.; Jerez-Calero, A.; García-Serrano, J. L.

    2015-01-01

    Objective. The goals were to isolate and study the genetic susceptibility to retinopathy of prematurity (ROP), as well as the gene-environment interaction established in this disease. Methods. A retrospective study (2000–2014) was performed about the heritability of retinopathy of prematurity in 257 infants who were born at a gestational age of ≤32 weeks. The ROP was studied and treated by a single pediatric ophthalmologist. A binary logistic regression analysis was completed between the presence or absence of ROP and the predictor variables. Results. Data obtained from 38 monozygotic twins, 66 dizygotic twins, and 153 of simple birth were analyzed. The clinical features of the cohorts of monozygotic and dizygotic twins were not significantly different. Genetic factors represented 72.8% of the variability in the stage of ROP, environmental factors 23.08%, and random factors 4.12%. The environmental variables representing the highest risk of ROP were the number of days of tracheal intubation (p < 0.001), postnatal weight gain (p = 0.001), and development of sepsis (p = 0.0014). Conclusion. The heritability of ROP was found to be 0.73. The environmental factors regulate and modify the expression of the genetic code. PMID:26089603

  8. Human thymic epithelial cells express functional HLA-DP molecules

    DEFF Research Database (Denmark)

    Jørgensen, A; Röpke, C; Nielsen, M

    1996-01-01

    T lymphocytes, we examined whether human thymic epithelial cells (TEC) expressed HLA-DP molecules. We present evidence that TEC obtained from short time culture express low but significant levels of HLA-DP molecules. The expression of HLA-DP molecules was comparable to or higher than the expression...... of HLA-DP allospecific primed lymphocyte typing (PLT) CD4 T cell lines. IFN-gamma treatment strongly upregulated the HLA-DP allospecific PLT responses whereas other PLT responses remained largely unchanged. In conclusion, these data indicate that human thymus epithelial cells express significant levels...

  9. Impact of enteral protein supplementation in premature infants

    Directory of Open Access Journals (Sweden)

    Barrus DM

    2012-06-01

    Full Text Available David M Barrus1, Joann Romano-Keeler2, Christopher Carr3, Kira Segebarth4, Betty Claxton2, William F Walsh2, Paul J Flakoll51Department of Neonatology, Saint Francis Hospital–Bartlett, Memphis, TN, 2Department of Pediatrics, Vanderbilt Medical Center, Nashville, TN, 3Department of Surgery, Naval Hospital Bremerton, Bremerton, WA, 4Pediatric and Diabetes Specialists, Carolinas Medical Center, Charlotte, NC, 5Department of Surgery, Vanderbilt Medical Center, Nashville, TN, USAObjective: The quantity of enteral protein supplementation required by premature infants to optimize growth has not been determined. This study compares the growth of premature infants fed the current standard intake of protein (3.5 g/kg/day with the growth of those fed a higher amount (4.0 g/kg/day.Study design: Fifty-two infants <1500 g and <33 weeks gestational age participated in a blinded, single-center, prospective randomized control trial to compare growth between two groups of different protein-intake levels. Primary outcomes were average daily weight gain (g/kg/day, head-circumference (cm/kg/week and linear growth velocity (cm/kg/week. Secondary outcomes were serum indices of protein tolerance and plasma amino acid concentrations.Results: Infants receiving higher amounts of protein had higher rates of growth for body weight (18.2 ± 0.7 versus 16.2 ± 1.0 g/kg/day; P < 0.05 and head circumference (0.87 ± 0.08 versus 0.62 ± 0.07 cm/kg/week; P < 0.05, with no differences in blood protein or plasma amino acid concentrations. Length of hospital stay was 14 days shorter for the higher-protein group (51.4 ± 4.0 versus 65.9 ± 6.3 days.Conclusion: Increasing premature infant enteral protein supplementation from a calculated intake of 3.5–4.0 g/kg/day improved growth in a safe manner.Keywords: human milk, human milk fortifier, growth, low birth weight

  10. Downregulation of Clusterin Expression in Human Testicular Seminoma

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    Bianjiang Liu

    2013-11-01

    Full Text Available Background: Clusterin, a heterodimeric glycoprotein of approximately 80 kDa, exists extensively in human body fluids. The abnormal expression of clusterin is closely related to the occurrence, progression, and prognosis of tumors. Up to now, few studies have focused on clusterin in human testicular cancer. This study describes an extensive exploration of the presence and expression of clusterin in testicular seminoma. Methods: Tumor tissues and normal testis tissues were collected from 13 patients with testicular seminoma and 16 patients undergoing surgical castration for prostate cancer. Real-time polymerase chain reaction (PCR was performed to detect the expression difference of clusterin mRNA between testicular seminoma and normal testis. Western blot and immunohistochemical analysis were performed to detect the presence and expression difference of clusterin protein between two groups. Results: Real-time PCR showed the expression of clusterin mRNA in testicular seminoma to be significantly lower than in normal testis (only 13% relative quantification. Western blot analysis indicated marked reductions in the expression of clusterin protein in testicular seminoma. Similar results were observed upon immunohistochemical analysis. Conclusion: In testicular seminoma and normal testis, clusterin exists in its heterodimeric secretory isoform. Clusterin expression is significantly lower in testicular seminoma than in normal testis. This is the first comprehensive study of the presence and expression of clusterin in human testicular cancer.

  11. Comparative Effects of Biodynes, Tocotrienol-Rich Fraction, and Tocopherol in Enhancing Collagen Synthesis and Inhibiting Collagen Degradation in Stress-Induced Premature Senescence Model of Human Diploid Fibroblasts

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    Jam, Faidruz Azura; Ismail, Zahariah; Wan Ngah, Wan Zurinah

    2013-01-01

    Biodynes, tocotrienol-rich fraction (TRF), and tocopherol have shown antiaging properties. However, the combined effects of these compounds on skin aging are yet to be investigated. This study aimed to elucidate the skin aging effects of biodynes, TRF, and tocopherol on stress-induced premature senescence (SIPS) model of human diploid fibroblasts (HDFs) by determining the expression of collagen and MMPs at gene and protein levels. Primary HDFs were treated with biodynes, TRF, and tocopherol prior to hydrogen peroxide (H2O2) exposure. The expression of COL1A1, COL3A1, MMP1, MMP2, MMP3, and MMP9 genes was determined by qRT-PCR. Type I and type III procollagen proteins were measured by Western blotting while the activities of MMPs were quantified by fluorometric Sensolyte MMP Kit. Our results showed that biodynes, TRF, and tocopherol upregulated collagen genes and downregulated MMP genes (P < 0.05). Type I procollagen and type III procollagen protein levels were significantly increased in response to biodynes, TRF, and tocopherol treatment (P < 0.05) with reduction in MMP-1, MMP-2, MMP-3, and MMP-9 activities (P < 0.05). These findings indicated that biodynes, TRF, and tocopherol effectively enhanced collagen synthesis and inhibited collagen degradation and therefore may protect the skin from aging. PMID:24396567

  12. Comparative Effects of Biodynes, Tocotrienol-Rich Fraction, and Tocopherol in Enhancing Collagen Synthesis and Inhibiting Collagen Degradation in Stress-Induced Premature Senescence Model of Human Diploid Fibroblasts

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    Suzana Makpol

    2013-01-01

    Full Text Available Biodynes, tocotrienol-rich fraction (TRF, and tocopherol have shown antiaging properties. However, the combined effects of these compounds on skin aging are yet to be investigated. This study aimed to elucidate the skin aging effects of biodynes, TRF, and tocopherol on stress-induced premature senescence (SIPS model of human diploid fibroblasts (HDFs by determining the expression of collagen and MMPs at gene and protein levels. Primary HDFs were treated with biodynes, TRF, and tocopherol prior to hydrogen peroxide (H2O2 exposure. The expression of COL1A1, COL3A1, MMP1, MMP2, MMP3, and MMP9 genes was determined by qRT-PCR. Type I and type III procollagen proteins were measured by Western blotting while the activities of MMPs were quantified by fluorometric Sensolyte MMP Kit. Our results showed that biodynes, TRF, and tocopherol upregulated collagen genes and downregulated MMP genes (P<0.05. Type I procollagen and type III procollagen protein levels were significantly increased in response to biodynes, TRF, and tocopherol treatment (P<0.05 with reduction in MMP-1, MMP-2, MMP-3, and MMP-9 activities (P<0.05. These findings indicated that biodynes, TRF, and tocopherol effectively enhanced collagen synthesis and inhibited collagen degradation and therefore may protect the skin from aging.

  13. Neuromodulation of Limb Proprioceptive Afferents Decreases Apnea of Prematurity and Accompanying Intermittent Hypoxia and Bradycardia.

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    Kesavan, Kalpashri; Frank, Paul; Cordero, Daniella M; Benharash, Peyman; Harper, Ronald M

    2016-01-01

    Apnea of Prematurity (AOP) is common, affecting the majority of infants born at Apnea and periodic breathing are accompanied by intermittent hypoxia (IH). Animal and human studies demonstrate that IH exposure contributes to multiple pathologies, including retinopathy of prematurity (ROP), injury to sympathetic ganglia regulating cardiovascular action, impaired pancreatic islet cell and bone development, cerebellar injury, and neurodevelopmental disabilities. Current standard of care for AOP/IH includes prone positioning, positive pressure ventilation, and methylxanthine therapy; these interventions are inadequate, and not optimal for early development. The objective is to support breathing in premature infants by using a simple, non-invasive vibratory device placed over limb proprioceptor fibers, an intervention using the principle that limb movements trigger reflexive facilitation of breathing. Premature infants (23-34 wks gestational age), with clinical evidence of AOP/IH episodes were enrolled 1 week after birth. Caffeine treatment was not a reason for exclusion. Small vibration devices were placed on one hand and one foot and activated in 6 hour ON/OFF sequences for a total of 24 hours. Heart rate, respiratory rate, oxygen saturation (SpO2), and breathing pauses were continuously collected. Fewer respiratory pauses occurred during vibration periods, relative to baseline (papnea, bradycardia and intermittent hypoxia in premature neonates. ClinicalTrials.gov NCT02641249.

  14. Retinopathy of prematurity

    International Nuclear Information System (INIS)

    Benavides Vargas, Ana Maria

    2013-01-01

    Retinopathy of prematurity has been the leading cause of childhood blindness. Early and effective screening has helped to diagnose the visual target of an infant by the difference between growing up with a disability or not. A joint effort between ophthalmologists and neonatologists is proposed to control this disease, ensuring success. An appropriate, early, effective and timely treatment has been the laser and cryotherapy like good choices for the neonate to prevent disease progression. Evaluation of screening program, to determine the incidence, compare statistics variables have been measures as other medical pathologies should be encouraged as research topics. A decrease in the incidence of retinopathy of prematurity is expected, controlling the risk factors during the child's stay in intrahospital neonatal unit [es

  15. Prematurely terminated slug tests

    International Nuclear Information System (INIS)

    Karasaki, K.

    1990-07-01

    A solution of the well response to a prematurely terminated slug test (PTST) is presented. The advantages of a PTST over conventional slug tests are discussed. A systematized procedure of a PTST is proposed, where a slug test is terminated in the midpoint of the flow point, and the subsequent shut-in data is recorded and analyzed. This method requires a downhole shut-in device and a pressure transducer, which is no more than the conventional deep-well slug testing. As opposed to slug tests, which are ineffective when a skin is present, more accurate estimate of formation permeability can be made using a PTST. Premature termination also shortens the test duration considerably. Because in most cases no more information is gained by completing a slug test to the end, the author recommends that conventional slug tests be replaced by the premature termination technique. This study is part of an investigation of the feasibility of geologic isolation of nuclear wastes being carried out by the US Department of Energy and the National Cooperative for the Storage of Radioactive Waste of Switzerland

  16. Behavioral and dermatologic changes and low serum zinc and copper concentrations in two premature infants after parenteral alimentation.

    Science.gov (United States)

    Sivasubramanian, K N; Henkin, R I

    1978-11-01

    Two premature infants were observed to develop behavioral and dermatologic changes and low serum zinc and copper concentrations following cessation of prolonged parenteral alimentation, while being fed exclusively with human milk. Following treatment with exogenous oral zinc supplementation, prompt relief of symptoms and increases of serum zinc and copper concentrations were observed in both infants. These patients comprise about 5% of our premature infants who are treated with parenteral alimentation for more than two weeks. We recommend that premature infants on prolonged parenteral alimentation should be monitored for changes in serum zinc and copper concentrations and, if a marked fall is observed, supplementation should be considered.

  17. Interpersonal problems as predictors of alliance, symptomatic improvement and premature termination in treatment of depression.

    Science.gov (United States)

    Dinger, Ulrike; Zilcha-Mano, Sigal; McCarthy, Kevin S; Barrett, Marna S; Barber, Jacques P

    2013-11-01

    Previous studies reported inconsistent findings regarding the association of interpersonal problems with therapy outcome. The current study investigates if interpersonal problems predict process and outcome of three different treatments for depression. The data originate from a randomized clinical trial comparing supportive-expressive psychotherapy, antidepressant medication and pill-placebo for treatment of depression. Interpersonal problems were used as predictors of alliance, symptomatic improvement and premature termination of treatment. Interpersonal problems related to communion predicted better alliances, but slower symptomatic improvement. Low agency predicted slower symptomatic improvement in supportive-expressive psychotherapy, but not in the medication or placebo condition. Lower interpersonal distress was associated with an increased likelihood to terminate treatment prematurely. The sample size did not allow the detection of small effects within the treatment groups. Interpersonal problems are influential for the treatment of depression, but parts of their effects depend on the type of treatment. © 2013 Elsevier B.V. All rights reserved.

  18. Risk Factors for premature birth in a hospital

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    Margarita E. Ahumada-Barrios

    Full Text Available Abstract Objective: to determine the risk factors for premature birth. Methods: retrospective case-control study of 600 pregnant women assisted in a hospital, with 298 pregnant women in the case group (who gave birth prematurely <37 weeks and 302 pregnant women who gave birth to a full-term newborn in the control group. Stata software version 12.2 was used. The Chi-square test was used in bivariate analysis and logistic regression was used in multivariate analysis, from which Odds Ratios (OR and Confidence Intervals (CI of 95% were derived. Results: risk factors associated with premature birth were current twin pregnancy (adjusted OR= 2.4; p= 0.02, inadequate prenatal care (< 6 controls (adjusted OR= 3.2; p <0.001, absent prenatal care (adjusted OR= 3.0; p <0.001, history of premature birth (adjusted OR= 3.7; p <0.001 and preeclampsia (adjusted OR= 1.9; p= 0.005. Conclusion: history of premature birth, preeclampsia, not receiving prenatal care and receiving inadequate prenatal care were risk factors for premature birth.

  19. (Unreceptiveness in interactions with professionals: experiences of parents of children with retinopathy of prematurity

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    Beatriz Castanheira Facio

    Full Text Available Abstract OBJECTIVE To analyze the influence of health professionals' receptiveness on parental care of children with retinopathy of prematurity (ROP. METHOD A qualitative study developed under the theoretical framework of Symbolic Interactionism and using a narrative research methodology. Six women and three men, being parents of children with retinopathy of prematurity were individually interviewed in depth. RESULTS From the scope of information, emotions and their rights, the parents experienced receptiveness from some professionals and unreceptiveness from others. The predominance of unreceptive attitudes in the parental narratives originated the following analysis themes: Informational (unreceptiveness, Emotional (unreceptiveness, and (Unreceptiveness of rights. CONCLUSION The study supports human and comprehensive healthcare in the context of retinopathy of prematurity by pointing out the interactive process with health professionals as a potential stressor of parental care. The results signal a nuclear of attitudinal changes and reinforce challenges to the child and family-centered approach.

  20. Frequency of neonatal complications after premature delivery

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    Gordana Grgić

    2013-04-01

    Full Text Available Introduction: Preterm delivery is the delivery before 37 weeks of gestation are completed. The incidence of preterm birth ranges from 5 to 15%. Aims of the study were to determine the average body weight, Apgar score after one and five minutes, and the frequency of the most common complications in preterminfants.Methods: The study involved a total of 631 newborns, of whom 331 were born prematurely Aims of this study were to (24th-37th gestational weeks-experimental group, while 300 infants were born in time (37-42 weeks of gestation-control group.Results: Average body weight of prematurely born infants was 2382 grams, while the average Apgar score in this group after the fi rst minute was 7.32 and 7.79 after the fifth minute. The incidence of respiratory distress syndrome was 50%, intracranial hemorrhage, 28.1% and 4.8% of sepsis. Respiratory distresssyndrome was more common in infants born before 32 weeks of gestation. Mortality of premature infants is present in 9.1% and is higher than that of infants born at term.Conclusions: Birth body weight and Apgar scores was lower in preterm infants. Respiratory distress syndrome is the most common fetal complication of prematurity. Intracranial hemorrhage is the second most common complication of prematurity. Mortality of premature infants is higher than the mortality of infants born at term birth.

  1. Lentivirus display: stable expression of human antibodies on the surface of human cells and virus particles.

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    Ran Taube

    Full Text Available BACKGROUND: Isolation of human antibodies using current display technologies can be limited by constraints on protein expression, folding and post-translational modifications. Here we describe a discovery platform that utilizes self-inactivating (SIN lentiviral vectors for the surface display of high-affinity single-chain variable region (scFv antibody fragments on human cells and lentivirus particles. METHODOLOGY/PRINCIPAL FINDINGS: Bivalent scFvFc human antibodies were fused in frame with different transmembrane (TM anchoring moieties to allow efficient high-level expression on human cells and the optimal TM was identified. The addition of an eight amino acid HIV-1 gp41 envelope incorporation motif further increased scFvFc expression on human cells and incorporation into lentiviral particles. Both antibody-displaying human cells and virus particles bound antigen specifically. Sulfation of CDR tyrosine residues, a property recently shown to broaden antibody binding affinity and antigen recognition was also demonstrated. High level scFvFc expression and stable integration was achieved in human cells following transduction with IRES containing bicistronic SIN lentivectors encoding ZsGreen when scFvFc fusion proteins were expressed from the first cassette. Up to 10(6-fold enrichment of antibody expressing cells was achieved with one round of antigen coupled magnetic bead pre-selection followed by FACS sorting. Finally, the scFvFc displaying human cells could be used directly in functional biological screens with remarkable sensitivity. CONCLUSIONS/SIGNIFICANCE: This antibody display platform will complement existing technologies by virtue of providing properties unique to lentiviruses and antibody expression in human cells, which, in turn, may aid the discovery of novel therapeutic human mAbs.

  2. Atrazine enhances progesterone production through activation of multiple signaling pathways in FSH-stimulated rat granulosa cells: evidence for premature luteinization.

    Science.gov (United States)

    Pogrmic-Majkic, Kristina; Samardzija, Dragana; Fa, Svetlana; Hrubik, Jelena; Glisic, Branka; Kaisarevic, Sonja; Andric, Nebojsa

    2014-11-01

    Premature luteinization is a possible cause of infertility in women. It is currently unknown whether environmental chemicals can induce changes associated with premature luteinization. Using rat granulosa cells (GC) in vitro, we demonstrated that exposure to atrazine (ATR), a widely used herbicide, causes GC phenotype that resembles that of human premature luteinization. At the end of the 48-h stimulation with FSH, ATR-exposed GC showed (1) higher levels of progesterone, (2) overexpression of luteal markers (Star and Cyp11a1), and (3) an increase in progesterone:estradiol ratio above 1. Mechanistic experiments were conducted to understand the signaling events engaged by ATR that lead to this phenotype. Western blot analysis revealed prolonged phosphorylation of protein kinase B (AKT) and cAMP response element-binding protein (CREB) in ATR- and FSH-exposed GC. An increased level of ERK1/2-dependent transcriptional factor CCATT/enhancer-binding protein beta (CEBPB) was observed after 4 h of ATR exposure. Inhibitors of PI3K (wortmannin) and MEK (U0126) prevented ATR-induced rise in progesterone level and expression of luteal markers in FSH-stimulated GC. Atrazine intensified AKT and CEBPB signaling and caused Star overexpression in forskolin-stimulated GC but not in epidermal growth factor (EGF)-stimulated GC. In the presence of rolipram, a specific inhibitor of phosphodiesterase 4 (PDE4), ATR was not able to further elevate AKT phosphorylation, CEBPB protein level, and Star mRNA in FSH-stimulated GC, suggesting that ATR inhibits PDE4. Overall, this study showed that ATR acts as a FSH sensitizer leading to enhanced cAMP, AKT, and CEBPB signaling and progesterone biosynthesis, which promotes premature luteinization phenotype in GC. © 2014 by the Society for the Study of Reproduction, Inc.

  3. The preterm cervix reveals a transcriptomic signature in the presence of premature prelabor rupture of membranes.

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    Makieva, Sofia; Dubicke, Aurelija; Rinaldi, Sara F; Fransson, Emma; Ekman-Ordeberg, Gunvor; Norman, Jane E

    2017-06-01

    Premature prelabor rupture of fetal membranes accounts for 30% of all premature births and is associated with detrimental long-term infant outcomes. Premature cervical remodeling, facilitated by matrix metalloproteinases, may trigger rupture at the zone of the fetal membranes overlying the cervix. The similarities and differences underlying cervical remodeling in premature prelabor rupture of fetal membranes and spontaneous preterm labor with intact membranes are unexplored. We aimed to perform the first transcriptomic assessment of the preterm human cervix to identify differences between premature prelabor rupture of fetal membranes and preterm labor with intact membranes and to compare the enzymatic activities of matrix metalloproteinases-2 and -9 between premature prelabor rupture of fetal membranes and preterm labor with intact membranes. Cervical biopsies were collected following preterm labor with intact membranes (n = 6) and premature prelabor rupture of fetal membranes (n = 5). Biopsies were also collected from reference groups at term labor (n = 12) or term not labor (n = 5). The Illumina HT-12 version 4.0 BeadChips microarray was utilized, and a novel network graph approach determined the specificity of changes between premature prelabor rupture of fetal membranes and preterm labor with intact membranes. Quantitative reverse transcription-polymerase chain reaction and Western blotting confirmed the microarray findings. Immunofluorescence was used for localization studies and gelatin zymography to assess matrix metalloproteinase activity. PML-RARA-regulated adapter molecule 1, FYVE-RhoGEF and PH domain-containing protein 3 and carcinoembryonic antigen-ralated cell adhesion molecule 3 were significantly higher, whereas N-myc downstream regulated gene 2 was lower in the premature prelabor rupture of fetal membranes cervix when compared with the cervix in preterm labor with intact membranes, term labor, and term not labor. PRAM1 and CEACAM3 were localized

  4. Lateralization for dynamic facial expressions in human superior temporal sulcus.

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    De Winter, François-Laurent; Zhu, Qi; Van den Stock, Jan; Nelissen, Koen; Peeters, Ronald; de Gelder, Beatrice; Vanduffel, Wim; Vandenbulcke, Mathieu

    2015-02-01

    Most face processing studies in humans show stronger activation in the right compared to the left hemisphere. Evidence is largely based on studies with static stimuli focusing on the fusiform face area (FFA). Hence, the pattern of lateralization for dynamic faces is less clear. Furthermore, it is unclear whether this property is common to human and non-human primates due to predisposing processing strategies in the right hemisphere or that alternatively left sided specialization for language in humans could be the driving force behind this phenomenon. We aimed to address both issues by studying lateralization for dynamic facial expressions in monkeys and humans. Therefore, we conducted an event-related fMRI experiment in three macaques and twenty right handed humans. We presented human and monkey dynamic facial expressions (chewing and fear) as well as scrambled versions to both species. We studied lateralization in independently defined face-responsive and face-selective regions by calculating a weighted lateralization index (LIwm) using a bootstrapping method. In order to examine if lateralization in humans is related to language, we performed a separate fMRI experiment in ten human volunteers including a 'speech' expression (one syllable non-word) and its scrambled version. Both within face-responsive and selective regions, we found consistent lateralization for dynamic faces (chewing and fear) versus scrambled versions in the right human posterior superior temporal sulcus (pSTS), but not in FFA nor in ventral temporal cortex. Conversely, in monkeys no consistent pattern of lateralization for dynamic facial expressions was observed. Finally, LIwms based on the contrast between different types of dynamic facial expressions (relative to scrambled versions) revealed left-sided lateralization in human pSTS for speech-related expressions compared to chewing and emotional expressions. To conclude, we found consistent laterality effects in human posterior STS but not

  5. Path analysis of risk factors leading to premature birth.

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    Fields, S J; Livshits, G; Sirotta, L; Merlob, P

    1996-01-01

    The present study tested whether various sociodemographic, anthropometric, behavioral, and medical/physiological factors act in a direct or indirect manner on the risk of prematurity using path analysis on a sample of Israeli births. The path model shows that medical complications, primarily toxemia, chorioammionitis, and a previous low birth weight delivery directly and significantly act on the risk of prematurity as do low maternal pregnancy weight gain and ethnicity. Other medical complications, including chronic hypertension, preclampsia, and placental abruption, although significantly correlated with prematurity, act indirectly on prematurity through toxemia. The model further shows that the commonly accepted sociodemographic, anthropometric, and behavioral risk factors act by modifying the development of medical complications that lead to prematurity as opposed to having a direct effect on premature delivery. © 1996 Wiley-Liss, Inc. Copyright © 1996 Wiley-Liss, Inc.

  6. Brucella abortus Induces the Premature Death of Human Neutrophils through the Action of Its Lipopolysaccharide

    Science.gov (United States)

    Barquero-Calvo, Elías; Mora-Cartín, Ricardo; Arce-Gorvel, Vilma; de Diego, Juana L.; Chacón-Díaz, Carlos; Chaves-Olarte, Esteban; Guzmán-Verri, Caterina; Buret, Andre G.; Gorvel, Jean-Pierre; Moreno, Edgardo

    2015-01-01

    Most bacterial infections induce the activation of polymorphonuclear neutrophils (PMNs), enhance their microbicidal function, and promote the survival of these leukocytes for protracted periods of time. Brucella abortus is a stealthy pathogen that evades innate immunity, barely activates PMNs, and resists the killing mechanisms of these phagocytes. Intriguing clinical signs observed during brucellosis are the low numbers of Brucella infected PMNs in the target organs and neutropenia in a proportion of the patients; features that deserve further attention. Here we demonstrate that B. abortus prematurely kills human PMNs in a dose-dependent and cell-specific manner. Death of PMNs is concomitant with the intracellular Brucella lipopolysaccharide (Br-LPS) release within vacuoles. This molecule and its lipid A reproduce the premature cell death of PMNs, a phenomenon associated to the low production of proinflammatory cytokines. Blocking of CD14 but not TLR4 prevents the Br-LPS-induced cell death. The PMNs cell death departs from necrosis, NETosis and classical apoptosis. The mechanism of PMN cell death is linked to the activation of NADPH-oxidase and a modest but steadily increase of ROS mediators. These effectors generate DNA damage, recruitments of check point kinase 1, caspases 5 and to minor extent of caspase 4, RIP1 and Ca++ release. The production of IL-1β by PMNs was barely stimulated by B. abortus infection or Br-LPS treatment. Likewise, inhibition of caspase 1 did not hamper the Br-LPS induced PMN cell death, suggesting that the inflammasome pathway was not involved. Although activation of caspases 8 and 9 was observed, they did not seem to participate in the initial triggering mechanisms, since inhibition of these caspases scarcely blocked PMN cell death. These findings suggest a mechanism for neutropenia in chronic brucellosis and reveal a novel Brucella-host cross-talk through which B. abortus is able to hinder the innate function of PMN. PMID:25946018

  7. Radiation-induced premature menopause: a misconception

    International Nuclear Information System (INIS)

    Madsen, Berit L.; Giudice, Linda; Donaldson, Sarah S.

    1995-01-01

    Purpose: To disprove the common view that women who have undergone irradiation to fields excluding the pelvis are at risk for radiation-induced premature menopause, we reviewed menstrual function and fertility among women treated with subtotal lymphoid irradiation for Hodgkin's Disease. Methods and Materials: Treatment and follow-up records of all women less than age 50 at the time of diagnosis of Stage I or II supradiaphragmatic Hodgkin's Disease, treated with subtotal lymphoid irradiation alone and enrolled in radiotherapy trials from 1967 to 1985, were reviewed. In addition, patients were surveyed regarding their menstrual status and fertility history. Results: Thirty-six women, aged 10 to 40 years, with normal menstrual function at the time of Hodgkin's diagnosis, were identified. Mean follow-up was 14 years, with a range of 1.25-22.75 years. The average radiation dose to mantle and paraaortic fields was 40-44 Gy; the calculated scatter radiation dose to the pelvis at the ovaries was 3.2 Gy. There were 38 pregnancies in 18 women; all offspring are normal. One of 36 women (2.7%) experienced premature menopause. The reported rate of premature menopause in women who have not undergone irradiation is 1-3%; not significantly different than the rate in our study. There is a syndrome whereby antibodies to several endocrine organs occur (including the ovary), which is associated with premature ovarian failure. This syndrome may be associated with prior radiation to the thyroid, such as that given by mantle-irradiation for Hodgkin's Disease. We report such a case. Conclusion: There is little risk of premature menopause in women treated with radiation fields that exclude the pelvis. Women with presumed radiation-induced premature menopause warrant an evaluation to exclude other causes of ovarian failure, such as autoimmune disorders

  8. Neuroglobin and Cytoglobin expression in the human brain

    DEFF Research Database (Denmark)

    Hundahl, Christian Ansgar; Kelsen, Jesper; Hay-Schmidt, Anders

    2013-01-01

    Neuroglobin and Cytoglobin are new members of the heme-globin family. Both globins are primarily expressed in neurons of the brain and retina. Neuroglobin and Cytoglobin have been suggested as novel therapeutic targets in various neurodegenerative diseases based on their oxygen binding and cell...... protecting properties. However, findings in Neuroglobin-deficient mice question the endogenous neuroprotective properties. The expression pattern of Neuroglobin and Cytoglobin in the rodent brain is also in contradiction to a major role of neuronal protection. In a recent study, Neuroglobin was ubiquitously...... expressed and up-regulated following stroke in the human brain. The present study aimed at confirming our previous observations in rodents using two post-mortem human brains. The anatomical localization of Neuroglobin and Cytoglobin in the human brain is much like what has been described for the rodent...

  9. Expression of Siglec-11 by human and chimpanzee ovarian stromal cells, with uniquely human ligands: implications for human ovarian physiology and pathology

    Science.gov (United States)

    Wang, Xiaoxia; Chow, Renee; Deng, Liwen; Anderson, Dan; Weidner, Noel; Godwin, Andrew K; Bewtra, Chanda; Zlotnik, Albert; Bui, Jack; Varki, Ajit; Varki, Nissi

    2011-01-01

    Siglecs (Sialic acid-binding Immunoglobulin Superfamily Lectins) are cell surface signaling receptors of the I-type lectin group that recognize sialic acid-bearing glycans. CD33-related-Siglecs are a subset with expression primarily in cells of hematopoietic origin and functional relevance to immune reactions. Earlier we reported a human-specific gene conversion event that markedly changed the coding region for the extracellular domain of Siglec-11, associated with human-specific expression in microglia (Hayakawa T, Angata T, Lewis AL, Mikkelsen TS, Varki NM, Varki A. 2005. A human-specific gene in microglia. Science. 309:1693). Analyzing human gene microarrays to define new patterns of expression, we observed high levels of SIGLEC11 transcript in the ovary and adrenal cortex. Thus, we examined human and chimpanzee tissues using a well-characterized anti-Siglec-11 mouse monoclonal antibody. Although adrenal expression was variable and confined to infiltrating macrophages in capillaries, ovarian expression of Siglec-11 in both humans and chimpanzees was on fibroblasts, the first example of Siglec expression on mesenchyme-derived stromal cells. Cytokines from such ovarian stromal fibroblasts play important roles in follicle development and ovulation. Stable transfection of SIGLEC11 into a primary human ovarian stromal fibroblast cell line altered the secretion of growth-regulated oncogene α, interleukin (IL)-10, IL-7, transforming growth factor β1 and tumor necrosis factor-α, cytokines involved in ovarian physiology. Probing for Siglec-11 ligands revealed distinct and strong mast cell expression in human ovaries, contrasting to diffuse stromal ligands in chimpanzee ovaries. Interestingly, there was a trend of increased Siglec-11 expression in post-menopausal ovaries compared with pre-menopausal ones. Siglec-11 expression was also found on human ovarian stromal tumors and in polycystic ovarian syndrome, a human-specific disease. These results indicate potential

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

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    Hoi-Hung Cheung

    2014-04-01

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

  11. Maternal assessment of pain in premature infants

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    Maria Carolina Correia dos Santos

    2015-12-01

    Full Text Available Objective: to identify mothers' perceptions about the pain in their premature babies in the Neonatal Intensive Care Unit. Methods: evaluative, quantitative study with investigative nature conducted with 19 mothers of hospitalized premature newborns. Data were obtained from closed questions, answered by mothers. Results: from the participants, two (10.5% reported that newborns are unable to feel pain. From the 17 mothers who said that premature babies can feel pain, the majority (94.1% identified crying as a characteristic of pain sensation. Eleven (64.7% stated that uneasiness is a sign of pain in newborns. Conclusion: for the proper management of neonatal pain it is essential that mothers know the signs of pain in premature newborns, and that health professionals instruct this recognition, through the enhancement of the maternal presence and practice of effective communication between professionals and newborns’ families.

  12. RESEARCHES RELATED TO THE REDUCTION OF PREMATURITY THROUGH PREMATURE RUPTURE OF MEMBRANES IN 2017

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    Maria BOLOTA

    2017-06-01

    Full Text Available Data from literature, especially from the US, has provided data on prediction, prevention and treatment of premature membrane rupture (RPM. RPM is a significant cause of premature birth and can cause complications of a term task. Considerable research on RPM has led to a better understanding of the mechanism of spontaneous breakage of membranes, risk factors, and good results for newborns resulting from such obstetrical events. Spontaneous rupture of the membranes increases the risk of intrauterine infection and umbilical cord compression as well as the risk of premature detachment of placenta. Newborn babies resulting from RPM have an increased risk of morbidity compared to gestational age, and the risk of infection is increased compared with other premature babies due to ancillary causes. If RPM occurs in the second trimester, there is an additional risk of pulmonary hypoplasia and hip dysplasia. Pre-term conservative treatment prolongs latency to birth. Antibiotics reduce the risk of infection while corticosteroid treatment (dexamethasone reduces respiratory complications and interventricular haemorrhage without increasing the risk of infection. Birth is necessary or unavoidable in many cases by RPMs and because conservative treatment often results in no results; That is why studies are needed to identify all risk factors and the need to treat pregnant women at risk of RPM; 17-hydroxy-progesterone is a specific treatment for preventing recurrent membrane rupture. (http://www.ginecologultau.ro/ruptura-prematura-a-membranelor, 2013.

  13. Induction of premature senescence by single and fractionated irradiation in human cancer cell line and xenografted mice model

    International Nuclear Information System (INIS)

    Yoo, Hee Jung; Kim, Bong Cho; Lee, Hyung Chul; Ji, Young Hoon; Park, Seung Woo; Lee, Jae Seon

    2011-01-01

    Radiation therapy (RT) is one of the best therapeutic strategies for cancer treatment. The cellular responses to ionizing radiation (IR) are varied ranging from cellular senescence to apoptotic cell death. To increase the efficacy of IR treatment is a major issue of radiation biology. From the point of view, the induction of premature senescence using the therapeutic dose of IR could be a promising treatment for tumors. The aim of this study is whether the premature senescence could contribute to cancer treatment by irradiation

  14. Symbolic transfer entropy-based premature signal analysis

    International Nuclear Information System (INIS)

    Wang Jun; Yu Zheng-Feng

    2012-01-01

    In this paper, we use symbolic transfer entropy to study the coupling strength between premature signals. Numerical experiments show that three types of signal couplings are in the same direction. Among them, normal signal coupling is the strongest, followed by that of premature ventricular contractions, and that of atrial premature beats is the weakest. The T test shows that the entropies of the three signals are distinct. Symbolic transfer entropy requires less data, can distinguish the three types of signals and has very good computational efficiency. (interdisciplinary physics and related areas of science and technology)

  15. Social support for parents of premature infants

    Directory of Open Access Journals (Sweden)

    Agnieszka Skurzak

    2018-03-01

    Full Text Available Prematurity is still an actual medical problem. Significant increase in the survival rate of premature babies is observed due to the progress in perinatal care .Usually, parents are not prepared for a premature birth, for the majority of them the hospitalization of a child in neonatal intensive care unit is a source of fear,  moreover parents often blame themselves for the situation. Appearing emotions and questions require a compatible response from the therapeutic team. The most important activity in the practice of the team is emotional, informative, evaluative support.

  16. Noninvasive Ventilation in Premature Neonates.

    Science.gov (United States)

    Flanagan, Keri Ann

    2016-04-01

    The use of noninvasive ventilation is a constantly evolving treatment option for respiratory disease in the premature infant. The goals of these noninvasive ventilation techniques are to improve gas exchange in the premature infant's lungs and to minimize the need for intubation and invasive mechanical ventilation. The goals of this article are to consider various uses of nasal interfaces, discuss skin care and developmental positioning concerns faced by the bedside nurse, and discuss the medical management aimed to reduce morbidity and mortality. This article explores the nursing role, the advances in medical strategies for noninvasive ventilation, and the team approach to noninvasive ventilation use in this population. Search strategy included a literature review on medical databases, such as EBSCOhost, CINAHL, PubMed, and NeoReviews. Innovative products, nursing research on developmental positioning and skin care, and advanced medical management have led to better and safer outcomes for premature infants requiring noninvasive ventilation. The medical focus of avoiding long-term mechanical ventilation would not be possible without the technology to provide noninvasive ventilation to these premature infants and the watchful eye of the nurse in terms of careful positioning, preventing skin breakdown and facial scarring, and a proper seal to maximize ventilation accuracy. This article encourages nursing-based research to quantify some of the knowledge about skin care and positioning as well as research into most appropriate uses for noninvasive ventilation devices.

  17. Human apolipoprotein B (apoB) mRNA: Identification of two distinct apoB mRNAs, an mRNA with the apoB-100 sequence and an apoB mRNA containing a premature in-frame translational stop codon, in both liver and intestine

    International Nuclear Information System (INIS)

    Higuchi, K.; Hospattankar, A.V.; Law, S.W.; Meglin, N.; Cortright, J.; Brewer, H.B. Jr.

    1988-01-01

    Human apolipoprotein B (apoB) is present in plasma as two separate isoproteins, designated apoB-100 (512 kDa) and apoB-48 (250 kDa). ApoB is encoded by a single gene on chromosome 2, and a single nuclear mRNA is edited and processed into two separate apoB mRNAs. A 14.1-kilobase apoB mRNA codes for apoB-100, and the second mRNA, which codes for apoB-48, contains a premature stop codon generated by a single base substitution of cytosine to uracil at nucleotide 6,538, which converts the translated CAA codon coding for the amino acid glutamine at residue 2,153 in apoB-100 to a premature in-frame stop codon (UAA). Two 30-base synthetic oligonucleotides, designated apoB-Stop and apoB-Gln, were synthesized containing the complementary sequence to the stop codon (UAA) and glutamine codon (CAA), respectively. The combined results from these studies establish that both human intestine and liver contain the two distinct apoB mRNAs, an mRNA that codes for apoB-100 and an apoB mRNA that contains the premature stop codon, which codes for apoB-48. The premature in-frame stop codon is not tissue specific and is present in both human liver and intestine

  18. RANK and RANK ligand expression in primary human osteosarcoma

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    Daniel Branstetter

    2015-09-01

    Our results demonstrate RANKL expression was observed in the tumor element in 68% of human OS using IHC. However, the staining intensity was relatively low and only 37% (29/79 of samples exhibited≥10% RANKL positive tumor cells. RANK expression was not observed in OS tumor cells. In contrast, RANK expression was clearly observed in other cells within OS samples, including the myeloid osteoclast precursor compartment, osteoclasts and in giant osteoclast cells. The intensity and frequency of RANKL and RANK staining in OS samples were substantially less than that observed in GCTB samples. The observation that RANKL is expressed in OS cells themselves suggests that these tumors may mediate an osteoclastic response, and anti-RANKL therapy may potentially be protective against bone pathologies in OS. However, the absence of RANK expression in primary human OS cells suggests that any autocrine RANKL/RANK signaling in human OS tumor cells is not operative, and anti-RANKL therapy would not directly affect the tumor.

  19. Astrocyte cultures derived from human brain tissue express angiotensinogen mRNA

    International Nuclear Information System (INIS)

    Milsted, A.; Barna, B.P.; Ransohoff, R.M.; Brosnihan, K.B.; Ferrario, C.M.

    1990-01-01

    The authors have identified human cultured cell lines that are useful for studying angiotensinogen gene expression and its regulation in the central nervous system. A model cell system of human central nervous system origin expressing angiotensinogen has not previously been available. Expression of angiotensinogen mRNA appears to be a basal property of noninduced human astrocytes, since astrocytic cell lines derived from human glioblastomas or nonneoplastic human brain tissue invariably produced angiotensinogen mRNA. In situ hybridization histochemistry revealed that angiotensinogen mRNA production was not limited to a subpopulation of astrocytes because >99% of cells in these cultures contained angiotensinogen mRNA. These cell lines will be useful in studies of the molecular mechanisms controlling angiotensin synthesis and the role of biologically active angiotensin in the human brain by allowing the authors to examine regulation of expression of the renin-angiotensin system in human astrocyte cultures

  20. Turning Avatar into Realistic Human Expression Using Linear and Bilinear Interpolations

    Science.gov (United States)

    Hazim Alkawaz, Mohammed; Mohamad, Dzulkifli; Rehman, Amjad; Basori, Ahmad Hoirul

    2014-06-01

    The facial animation in term of 3D facial data has accurate research support of the laser scan and advance 3D tools for complex facial model production. However, the approach still lacks facial expression based on emotional condition. Though, facial skin colour is required to offers an effect of facial expression improvement, closely related to the human emotion. This paper presents innovative techniques for facial animation transformation using the facial skin colour based on linear interpolation and bilinear interpolation. The generated expressions are almost same to the genuine human expression and also enhance the facial expression of the virtual human.

  1. Aggressive Posterior Retinopathy of Prematurity in a Premature Male Infant

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    Jun Zhou

    2017-07-01

    Full Text Available A premature male infant was born at 30 weeks’ gestation with a birth weight of 1,700 g in a rural hospital. He was diagnosed with respiratory distress syndrome and received continuous positive airway pressure treatment for 26 days. At 26 days after birth, the patient was transferred to our hospital for further evaluation and management. A comprehensive eye examination revealed a stage 3 retinopathy of prematurity (ROP involving zone 2 in both eyes. The patient was recommended to a provincial-level eye hospital for emergency laser therapy. Five months after birth, the feedback from the eye hospital showed that the patient had a high risk of blindness in both eyes. Our case report shows that delaying first screening examination increases the possibility of developing aggressive posterior ROP in infants with ROP. Doctors in rural hospitals should be aware of this possibility and trained for early screening and treatment in high-risk infants.

  2. Optimal oxygen saturation in premature infants

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    Meayoung Chang

    2011-09-01

    Full Text Available There is a delicate balance between too little and too much supplemental oxygen exposure in premature infants. Since underuse and overuse of supplemental oxygen can harm premature infants, oxygen saturation levels must be monitored and kept at less than 95% to prevent reactive oxygen species-related diseases, such as retinopathy of prematurity and bronchopulmonary dysplasia. At the same time, desaturation below 80 to 85% must be avoided to prevent adverse consequences, such as cerebral palsy. It is still unclear what range of oxygen saturation is appropriate for premature infants; however, until the results of further studies are available, a reasonable target for pulse oxygen saturation (SpO2 is 90 to 93% with an intermittent review of the correlation between SpO2 and the partial pressure of arterial oxygen tension (PaO2. Because optimal oxygenation depends on individuals at the bedside making ongoing adjustments, each unit must define an optimal target range and set alarm limits according to their own equipment or conditions. All staff must be aware of these values and adjust the concentration of supplemental oxygen frequently.

  3. Lactoferrin and prematurity: a promising milk protein?

    Science.gov (United States)

    Ochoa, Theresa J; Sizonenko, Stéphane V

    2017-02-01

    Lactoferrin (Lf) is the major whey protein in milk, with multiple beneficial health effects including direct antimicrobial activities, anti-inflammatory effects, and iron homeostasis. Oral Lf supplementation in human preterm infants has been shown to reduce the incidence of sepsis and necrotizing enterocolitis. In preclinical models of antenatal stress and perinatal brain injury, bovine Lf protected the developing brain from neuronal loss, improved connectivity, increased neurotrophic factors, and decreased inflammation. It also supported brain development and cognition. Further, Lf can prevent preterm delivery by reducing proinflammatory factors and inhibiting premature cervix maturation. We review here the latest research on Lf in the field of neonatology.

  4. Progranulin expression in advanced human atherosclerotic plaque.

    Science.gov (United States)

    Kojima, Yoji; Ono, Koh; Inoue, Katsumi; Takagi, Yasushi; Kikuta, Ken-ichiro; Nishimura, Masaki; Yoshida, Yoshinori; Nakashima, Yasuhiro; Matsumae, Hironobu; Furukawa, Yutaka; Mikuni, Nobuhiro; Nobuyoshi, Masakiyo; Kimura, Takeshi; Kita, Toru; Tanaka, Makoto

    2009-09-01

    Progranulin (PGRN) is a unique growth factor that plays an important role in cutaneous wound healing. It has an anti-inflammatory effect and promotes cell proliferation. However, when it is degraded to granulin peptides (GRNs) by neutrophil proteases, a pro-inflammatory reaction occurs. Since injury, inflammation and repair are common features in the progression of atherosclerosis, it is conceivable that PGRN plays a role in atherogenesis. Immunohistochemical analysis of human carotid endoatherectomy specimens indicated that vascular smooth muscle cells (vSMCs) in the intima expressed PGRN. Some macrophages in the plaque also expressed PGRN. We assessed the effect of PGRN on a human monocytic leukemia cell line (THP-1) and human aortic smooth muscle cells (HASMCs). PGRN alone had no effect on HASMC or THP-1 proliferation or migration. However, when THP-1 cells were stimulated with MCP-1, the number of migrated cells decreased in a PGRN-dose-dependent manner. TNF-alpha-induced HASMC migration was enhanced only at 10nM of PGRN. Interleukin-8 (IL-8) secretion from HASMCs was reduced by forced expression of PGRN and increased by RNAi-mediated knockdown of PGRN. While exogenous treatment with recombinant PGRN decreased IL-8 secretion, degraded recombinant GRNs increased IL-8 secretion from HASMCs. The expression of PGRN mainly reduces inflammation and its degradation into GRNs enhances inflammation in atherosclerotic plaque and may contribute to the progression of atherosclerosis.

  5. Extremely high concentration of folates in premature newborns.

    Science.gov (United States)

    Zikavska, T; Brucknerova, I

    2014-01-01

    Extremely high concentration of folates in premature newborns: case reports. Folates are a group of water soluble compounds, which are important for metabolic processes in human body. These are important during periods of rapid cell growth. The most accurate indicator of long-term folate level status in the body is the determination of red blood cell (RBC) folate concentrations. The optimal level of RBC folate is not known in neonatal period. Authors discuss the reasons for extremely high level of RBC folate concentrations. In our work we present the cases of two premature newborns with extremely high level of RBC folate concentrations, which were analyzed immunochemically on the first day of life and after six weeks of life. In both cases we measured RBC folate concentrations on the 1st day of life. After 6 weeks we found extremely high RBC folate concentration level (5516.67 ng/ml) in the first case after RBC transfusions. In second case after two months of life the RBC folate concentration level was doubled (2335.1 ng/ml) until 24 hours after RBC transfusion compared to levels after birth. The normal range of RBC folate values vary in newborns. The upper limit of daily dose of folic acid in pregnancy and neonatal period is not known. On the other hand it is an easily excreted water-soluble vitamin but in premature newborn it can lead to the disruption of metabolic balance and slow its degradation. Some factors can have an impact on RBC folate concentration. Blood transfusion can be one of the main influences on RBC folate concentration. To clarify these mechanisms further studies are required (Ref. 29).

  6. Bacterial expression of human kynurenine 3-monooxygenase: Solubility, activity, purification☆

    Science.gov (United States)

    Wilson, K.; Mole, D.J.; Binnie, M.; Homer, N.Z.M.; Zheng, X.; Yard, B.A.; Iredale, J.P.; Auer, M.; Webster, S.P.

    2014-01-01

    Kynurenine 3-monooxygenase (KMO) is an enzyme central to the kynurenine pathway of tryptophan metabolism. KMO has been implicated as a therapeutic target in several disease states, including Huntington’s disease. Recombinant human KMO protein production is challenging due to the presence of transmembrane domains, which localise KMO to the outer mitochondrial membrane and render KMO insoluble in many in vitro expression systems. Efficient bacterial expression of human KMO would accelerate drug development of KMO inhibitors but until now this has not been achieved. Here we report the first successful bacterial (Escherichia coli) expression of active FLAG™-tagged human KMO enzyme expressed in the soluble fraction and progress towards its purification. PMID:24316190

  7. Snail1 Expression Is Required for Sarcomagenesis

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    Lorena Alba-Castellón

    2014-05-01

    Full Text Available Snail1 transcriptional repressor is a major inducer of epithelial-to mesenchymal transition but is very limitedly expressed in adult animals. We have previously demonstrated that Snail1 is required for the maintenance of mesenchymal stem cells (MSCs, preventing their premature differentiation. Now, we show that Snail1 controls the tumorigenic properties of mesenchymal cells. Increased Snail1 expression provides tumorigenic capabilities to fibroblastic cells; on the contrary, Snail1 depletion decreases tumor growth. Genetic depletion of Snail1 in MSCs that are deficient in p53 tumor suppressor downregulates MSC markers and prevents the capability of these cells to originate sarcomas in immunodeficient SCID mice. Notably, an analysis of human sarcomas shows that, contrarily to epithelial tumors, these neoplasms display high Snail1 expression. This is particularly clear for undifferentiated tumors, which are associated with poor outcome. Together, our results indicate a role for Snail1 in the generation of sarcomas.

  8. [Family participation in premature care in neonatal ICU].

    Science.gov (United States)

    Gaíva, Maria Aparecida Munhoz; Scochi, Carmen Gracinda Silvan

    2005-01-01

    This study aimed at analyzing the family participation in the premature assistance in a university hospital neonatal ICU. Data were collected from the participant observation. Results showed that despite of the mother's presence in the daily life of their premature children placed in a hospital, family isn't inserted in the work process and mothers are the only ones who take part of the cares. This participation basically happens in the execution of maternity care, especially at the medium risk unity, the mother and premature family are less welcomed and there isn't any partnership between the care team and the family, there aren't team interventions in order to turn premature family in autonomous subject to promote health and life quality to baby's life.

  9. Dual-color fluorescence imaging to monitor CYP3A4 and CYP3A7 expression in human hepatic carcinoma HepG2 and HepaRG cells.

    Directory of Open Access Journals (Sweden)

    Saori Tsuji

    Full Text Available Human adult hepatocytes expressing CYP3A4, a major cytochrome P450 enzyme, are required for cell-based assays to evaluate the potential risk of drug-drug interactions caused by transcriptional induction of P450 enzymes in early-phase drug discovery and development. However, CYP3A7 is preferentially expressed in premature hepatoblasts and major hepatic carcinoma cell lines. The human hepatocellular carcinoma cell line HepaRG possesses a high self-renewal capacity and can differentiate into hepatic cells similar to human adult hepatocytes in vitro. Transgenic HepaRG cells, in which the expression of fluorescent reporters is regulated by 35 kb regulatory elements of CYP3A4, have a distinct advantage over human hepatocytes isolated by collagenase perfusion, which are unstable in culture. Thus, we created transgenic HepaRG and HepG2 cells by replacing the protein-coding regions of human CYP3A4 and CYP3A7 with enhanced green fluorescent protein (EGFP and DsRed reporters, respectively, in a bacterial artificial chromosome vector that included whole regulatory elements. The intensity of DsRed fluorescence was initially high during the proliferation of transgenic HepaRG cells. However, most EGFP-positive cells were derived from those in which DsRed fluorescence was extinguished. Comparative analyses in these transgenic clones showed that changes in the total fluorescence intensity of EGFP reflected fold changes in the mRNA level of endogenous CYP3A4. Moreover, CYP3A4 induction was monitored by the increase in EGFP fluorescence. Thus, this assay provides a real-time evaluation system for quality assurance of hepatic differentiation into CYP3A4-expressing cells, unfavourable CYP3A4 induction, and fluorescence-activated cell sorting-mediated enrichment of CYP3A4-expressing hepatocytes based on the total fluorescence intensities of fluorescent reporters, without the need for many time-consuming steps.

  10. Do the early development of gestures and receptive and expressive language predict language skills at 5;0 in prematurely born very-low-birth-weight children?

    Science.gov (United States)

    Stolt, S; Lind, A; Matomäki, J; Haataja, L; Lapinleimu, H; Lehtonen, L

    2016-01-01

    It is unclear what the predictive value of very early development of gestures and language is on later language ability in prematurely born very-low-birth-weight (VLBW; birth weight ≤1500g) children. The aim of the present study was to analyse the predictive value of early gestures and a receptive lexicon measured between the ages of 0;9 and 1;3, as well as the predictive value of receptive and expressive language ability at 2;0 for language skills at 5;0 in VLBW children. The subjects were 29 VLBW children and 28 full-term children whose language development has been followed intensively between the ages of 0;9 and 2;0 using the Finnish version of the MacArthur Developmental Inventory and the Reynell Developmental Language Scales (RDLS III). At 5;0, five selected verbal subtests of the Nepsy II test and the Boston Naming Test (BNT) were used to assess children's language skills. For the first time in VLBW children, the development of gestures measured between the ages of 0;9 and 1;3 was shown to correlate significantly and positively with language skills at 5;0. In addition, both receptive and expressive language ability measured at 2;0 correlated significantly and positively with later language skills in both groups. Moreover, according to the hierarchical regression analysis, the receptive language score of the RDLS III at 2;0 was a clear and significant predictor for language skills at 5;0 in both groups. The findings particularly underline the role of early receptive language as a significant predictor for later language ability in VLBW children. The results provide evidence for a continuity between early language development and later language skills. After reading this article, readers will understand the associations between the very early (≤2 years of age) development of gestures and language (i.e. early receptive lexicon, expressive lexicon at 2;0, receptive and expressive language ability at 2;0) and the language skills at 5;0 in prematurely born

  11. Risk Factors for premature birth in a hospital 1

    Science.gov (United States)

    Ahumada-Barrios, Margarita E.; Alvarado, German F.

    2016-01-01

    Abstract Objective: to determine the risk factors for premature birth. Methods: retrospective case-control study of 600 pregnant women assisted in a hospital, with 298 pregnant women in the case group (who gave birth prematurely <37 weeks) and 302 pregnant women who gave birth to a full-term newborn in the control group. Stata software version 12.2 was used. The Chi-square test was used in bivariate analysis and logistic regression was used in multivariate analysis, from which Odds Ratios (OR) and Confidence Intervals (CI) of 95% were derived. Results: risk factors associated with premature birth were current twin pregnancy (adjusted OR= 2.4; p= 0.02), inadequate prenatal care (< 6 controls) (adjusted OR= 3.2; p <0.001), absent prenatal care (adjusted OR= 3.0; p <0.001), history of premature birth (adjusted OR= 3.7; p <0.001) and preeclampsia (adjusted OR= 1.9; p= 0.005). Conclusion: history of premature birth, preeclampsia, not receiving prenatal care and receiving inadequate prenatal care were risk factors for premature birth. PMID:27463110

  12. Time trends and risk factor associated with premature birth and infants deaths due to prematurity in Hubei Province, China from 2001 to 2012.

    Science.gov (United States)

    Xu, Haiqing; Dai, Qiong; Xu, Yusong; Gong, Zhengtao; Dai, Guohong; Ding, Ming; Duggan, Christopher; Hu, Zubin; Hu, Frank B

    2015-12-10

    The nutrition and epidemiologic transition has been associated with an increasing incidence of preterm birth in developing countries, but data from large observational studies in China have been limited. Our study was to describe the trends and factors associated with the incidence of preterm birth and infant mortality due to prematurity in Hubei Province, China. We conducted a population-based survey through the Maternal and Child Health Care Network in Hubei Province from January 2001 to December 2012. We used data from 16 monitoring sites to examine the trend and risk factors for premature birth as well as infant mortality associated with prematurity. A total of 818,481 live births were documented, including 76,923 preterm infants (94 preterm infants per 1,000 live births) and 2,248 deaths due to prematurity (2.75 preterm deaths per 1,000 live births). From 2001 to 2012, the incidence of preterm birth increased from 56.7 to 105.2 per 1,000 live births (P for trend prematurity declined from 95.0 to 13.4 per 1,000 live births (P for trend prematurity were observed in Hubei Province from 2001 to 2012. Our results provide important information for areas of improvements in reducing incidence and mortality of premature birth.

  13. Biodosimetry of ionizing radiation by selective painting of prematurely condensed chromosomes in human lymphocytes

    Science.gov (United States)

    Durante, M.; George, K.; Yang, T. C.

    1997-01-01

    Painting of interphase chromosomes can be useful for biodosimetric purposes in particular cases such as radiation therapy, accidental exposure to very high radiation doses and exposure to densely ionizing radiation, for example during space missions. Biodosimetry of charged-particle radiation is analyzed in the present paper. Target cells were human peripheral blood lymphocytes irradiated in vitro with gamma rays, protons and iron ions. After exposure, lymphocytes were incubated for different times to allow repair of radiation-induced damage and then fused to mitotic hamster cells to promote premature condensation in the interphase chromosomes. Chromosome spreads were then hybridized with whole-chromosome DNA probes labeled with fluorescent stains. Dose-response curves for the induction of chromatin fragments shortly after exposure, as well as the kinetics of rejoining and misrejoining, were not markedly dependent on linear energy transfer. However, after exposure to heavy ions, more aberrations were scored in the interphase cells after incubation for repair than in metaphase samples harvested at the first postirradiation mitosis. On the other hand, no significant differences were observed in the two samples after exposure to sparsely ionizing radiation. These results suggest that interphase chromosome painting can be a useful tool for biodosimetry of particle radiation.

  14. Microarray expression profiling of human dental pulp from single subject.

    Science.gov (United States)

    Tete, Stefano; Mastrangelo, Filiberto; Scioletti, Anna Paola; Tranasi, Michelangelo; Raicu, Florina; Paolantonio, Michele; Stuppia, Liborio; Vinci, Raffaele; Gherlone, Enrico; Ciampoli, Cristian; Sberna, Maria Teresa; Conti, Pio

    2008-01-01

    Microarray is a recently developed simultaneous analysis of expression patterns of thousand of genes. The aim of this research was to evaluate the expression profile of human healthy dental pulp in order to find the presence of genes activated and encoding for proteins involved in the physiological process of human dental pulp. We report data obtained by analyzing expression profiles of human tooth pulp from single subjects, using an approach based on the amplification of the total RNA. Experiments were performed on a high-density array able to analyse about 21,000 oligonucleotide sequences of about 70 bases in duplicate, using an approach based on the amplification of the total RNA from the pulp of a single tooth. Obtained data were analyzed using the S.A.M. system (Significance Analysis of Microarray) and genes were merged according to their molecular functions and biological process by the Onto-Express software. The microarray analysis revealed 362 genes with specific pulp expression. Genes showing significant high expression were classified in genes involved in tooth development, protoncogenes, genes of collagen, DNAse, Metallopeptidases and Growth factors. We report a microarray analysis, carried out by extraction of total RNA from specimens of healthy human dental pulp tissue. This approach represents a powerful tool in the study of human normal and pathological pulp, allowing minimization of the genetic variability due to the pooling of samples from different individuals.

  15. Premature ejaculation: A clinical review for the general physician.

    Science.gov (United States)

    Chung, Eric; Gilbert, Brent; Perera, Marlon; Roberts, Matthew J

    2015-10-01

    Premature ejaculation is one of the most common sexual dysfunctions in men. Recent epidemiological studies suggest its prevalence in Australia may range from 21-31% This article will discuss the current definition of premature ejaculation from a urological perspective. It will provide an understanding of the pathogenesis of premature ejaculation, as well as assessment and management options. Premature ejaculation can have a significant adverse effect on the quality of life for the patient and his sexual partners. It can potentially lead to psychological distress, diminished self- esteem, anxiety, erectile dysfunction, reduced libido and poor interpersonal relationships. Most men feel reluctant to discuss premature ejaculation with their general practitioner despite its psychological, emotional and relational effects. Effective, evidence-based treatment options are available and physicians should feel confident when exploring ways to improve the quality of life for men with sexual dysfunction.

  16. Retinopathy of prematurity: an epidemic in the making.

    Science.gov (United States)

    Quinn, Graham E; Gilbert, Clare; Darlow, Brian A; Zin, Andrea

    2010-10-01

    To explore the etiology, incidence and methods to prevent and treat severe retinopathy of prematurity (ROP), which is rapidly becoming a threat to the vision of babies in areas of the world where increasing numbers of premature babies are surviving. The data used in this review were mainly from Medline and PubMed published in English. The search term was "retinopathy of prematurity and premature birth". We discuss the historical perspectives, prevalence and incidence, classification and treatment methods of ROP in premature babies. Peripheral retinal ablation for eyes with severe ROP can help prevent progression to blindness and several large clinical trials have shown the effectiveness of this treatment in high risk eyes. As a greater proportion of VLBW and ELBW babies survive, the population of babies at risk increases. In various regions of the world, different identification criteria are used to determine which babies are at risk of blindness in order to provide timely diagnostic examinations and treatment as needed. Methods for preventing ROP include better ante-natal and obstetric care leading to a reduction in the rate of prematurity, the use of ante-natal corticosteroids, and better neonatal care practices. Recent developments have indicated that management of oxygen supplementation is important for the prevention of severe ROP; however, there is not yet known what oxygen saturation target should be adopted. Sepsis increases severe ROP in very preterm infants. Genetic associations and a telemedicine approach may be explored to detect ROP. Treatment of anti-VEGF therapy are potentially useful in eyes with severe ROP, but long term effects are not yet known and such treatment should be used with great caution. ROP is a potentially binding disease for premature babies which is becoming more prevalent with the development improving neonatal services in many countries in recent years. High priority should be placed on developing approaches to prevent ROP

  17. Serbia within the European context: An analysis of premature mortality

    Directory of Open Access Journals (Sweden)

    Marinkovic Jelena

    2009-08-01

    diabetes mellitus. The results may be used for assessment of unacceptable social risks resulting from health inequalities. Within intentions to reduce an unfavourable premature mortality gap, it is necessary to reconsider certain local polices and practices as well as financial and human resources incorporated in the prevention of disease and injury burden.

  18. Relationship between serum 25-hydroxy vitamin D levels and retinopathy of prematurity.

    Science.gov (United States)

    Kabataş, Emrah Utku; Dinlen, Nurdan Fettah; Zenciroğlu, Ayşegül; Dilli, Dilek; Beken, Serdar; Okumuş, Nurullah

    2017-11-01

    Aim To evaluate the relationship between serum 25-hydroxy vitamin D, 25 (OH) D, levels and retinopathy of prematurity. Methods and Results Serum 25 (OH) D levels were measured in 97 very low birth weight infants, prior to vitamin D supplementation. The development of retinopathy of prematurity and its treatment requirement were evaluated. At follow-up, retinopathy of prematurity developed in 71 (73.2%) infants. Serum 25 (OH) D levels were significantly lower in infants with retinopathy of prematurity than ones without retinopathy of prematurity ( P prematurity development [OR: 1.14, 95% CI (1.02-1.27), P = 0.02]. Conclusion Lower 25 (OH) D levels in the first days of life may be related to retinopathy of prematurity development and treatment requirement in premature infants.

  19. Bacterial expression of human kynurenine 3-monooxygenase: solubility, activity, purification.

    Science.gov (United States)

    Wilson, K; Mole, D J; Binnie, M; Homer, N Z M; Zheng, X; Yard, B A; Iredale, J P; Auer, M; Webster, S P

    2014-03-01

    Kynurenine 3-monooxygenase (KMO) is an enzyme central to the kynurenine pathway of tryptophan metabolism. KMO has been implicated as a therapeutic target in several disease states, including Huntington's disease. Recombinant human KMO protein production is challenging due to the presence of transmembrane domains, which localise KMO to the outer mitochondrial membrane and render KMO insoluble in many in vitro expression systems. Efficient bacterial expression of human KMO would accelerate drug development of KMO inhibitors but until now this has not been achieved. Here we report the first successful bacterial (Escherichia coli) expression of active FLAG™-tagged human KMO enzyme expressed in the soluble fraction and progress towards its purification. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Expression of CD44 splice variants in human primary brain tumors

    NARCIS (Netherlands)

    Kaaijk, P.; Troost, D.; Morsink, F.; Keehnen, R. M.; Leenstra, S.; Bosch, D. A.; Pals, S. T.

    1995-01-01

    Expression of CD44, particularly of certain splice variants, has been linked to tumor progression and metastatic potential in a number of different animal and human cancers. Although differential expression of CD44 standard epitopes (CD44s) in human brain tumors has been reported, the expression of

  1. Decorin gene expression and its regulation in human keratinocytes

    Energy Technology Data Exchange (ETDEWEB)

    Velez-DelValle, Cristina; Marsch-Moreno, Meytha; Castro-Munozledo, Federico [Department of Cell Biology, Centro de Investigacion y de Estudios Avanzados del IPN, Apdo. Postal 14-740, Mexico D.F. 07000 (Mexico); Kuri-Harcuch, Walid, E-mail: walidkuri@gmail.com [Department of Cell Biology, Centro de Investigacion y de Estudios Avanzados del IPN, Apdo. Postal 14-740, Mexico D.F. 07000 (Mexico)

    2011-07-22

    Highlights: {yields} We showed that cultured human diploid epidermal keratinocytes express and synthesize decorin. {yields} Decorin is found intracytoplasmic in suprabasal cells of cultures and in human epidermis. {yields} Decorin mRNA expression in cHEK is regulated by pro-inflammatory and proliferative cytokines. {yields} Decorin immunostaining of psoriatic lesions showed a lower intensity and altered intracytoplasmic arrangements. -- Abstract: In various cell types, including cancer cells, decorin is involved in regulation of cell attachment, migration and proliferation. In skin, decorin is seen in dermis, but not in keratinocytes. We show that decorin gene (DCN) is expressed in the cultured keratinocytes, and the protein is found in the cytoplasm of differentiating keratinocytes and in suprabasal layers of human epidermis. RT-PCR experiments showed that DCN expression is regulated by pro-inflammatory and proliferative cytokines. Our data suggest that decorin should play a significant role in keratinocyte terminal differentiation, cutaneous homeostasis and dermatological diseases.

  2. Fractalkine is expressed in the human ovary and increases progesterone biosynthesis in human luteinised granulosa cells

    Directory of Open Access Journals (Sweden)

    Yan Jie

    2011-06-01

    Full Text Available Abstract Background Recent evidence from rodent ovaries has demonstrated expression of fractalkine and the existence of fractalkine receptor, and showed that there is a significant increase in steroidogenesis in response to fractalkine, yet the role of fractalkine and CX3CR1 in the human ovary is still unknown. This study aimed to determine the expression levels of fractalkine and CX3CR1 in the human ovary and to investigate their roles in sexual hormone biosynthesis by human luteinising granulosa cells. This is the first detailed report of fractalkine and CX3CR1 expression and function in the human ovary. Methods Fractalkine and CX3CR1 expression levels were measured by immunohistochemistry using ovarian tissue from pathological specimens from five individuals. Granulosa cells were obtained from patients during IVF treatment. They were cultured and treated with increasing doses of hCG with or without fractalkine. Media were collected to detect estradiol and progesterone by chemiluminescence. StAR, 3-βHSD and CYP11A expression were determined in granulosa cells treated with or without fractalkine by real-time RT-PCR. Results Fractalkine and CX3CR1 were expressed in the human ovary and in luteinising granulosa cells. However, fractalkine expression was stronger in luteinising granulosa cells. Treatment with fractalkine augmented hCG stimulation of progesterone production in a dose-dependent manner with concomitant increases in transcript levels for key steroidogenic enzymes (StAR, 3-βHSD and CYP11A but had no effect on estradiol biosynthesis(P Conclusions Fractalkine and CX3CR1 were found to express in human ovary and luteinising granulosa cells. Fractalkine can increase the biosynthesis of progesterone in a dose-dependent manner by enhancing transcript levels of key steroidogenic enzymes.

  3. [Birth weight distribution among premature infants and related social factors].

    Science.gov (United States)

    Guo, Li-jun; Ye, Rong-wei; Wang, Gui-xia; Wang, Juan; Li, Zhi-wen; Ren, Ai-guo

    2009-12-01

    To understand the distribution of birth weight among premature infants and the associated social factors. The study population consisted of 97 537 women who delivered singleton live birth of 20 to 41 gestational weeks in 4 counties/cities, Jiangsu and Zhejiang provinces, China from 1995 to 2000. Chi-square test was employed to test the difference of proportions between respective groups. One- way ANOVA was used to test the differences regarding the mean of gestational weeks at the first prenatal visit and the mean of prenatal visits between the two groups. Multivariate logistic regression was conducted to examine the factors associated with premature birth. Women aged 35 years had higher (8.8%) premature incidence than those aged less than 24 years (5.6%), 25 - 29 years (4.6%), or 30 - 34 years (4.5%, P premature incidence than those with height taller than 150 cm (5.0%). Women whose BMI were at least 28 and 24 - 28 had higher (5.5%, 5.5%) premature incidences than those whose BMI were 18.5 - 24.0 (5.0%), premature birth was 6.0% among women without previous pregnancy, higher than that among those women with 4 times of pregnancies (5.7%), 2 times of pregnancies (4.3%), and 3 times of pregnancies (4.0%). Parous women with at least two deliveries had higher (9.3%) premature incidence than the primiparous women (5.2%) and whose women with only one delivery (4.5%, P premature incidence than those who did not receive the service (6.1%). The mean times of prenatal visits among women with premature births was 8.53, less than that of those with full term delivery (10.97). Women with less than four times of prenatal visit had higher (18.9%) premature incidence than those with at least five prenatal visits (4.9%). Multivariate logistic regression showed that premature delivery risk was associated with age, height, BMI, gravidity, parity, early prenatal care, the mean of gestational weeks at first prenatal visit and the mean number of prenatal visits etc. Premature delivery

  4. The distribution of patients who seek treatment for the complaint of ejaculating prematurely according to the four premature ejaculation syndromes.

    Science.gov (United States)

    Serefoglu, Ege Can; Cimen, Haci Ibrahim; Atmaca, Ali Fuat; Balbay, M Derya

    2010-02-01

    In addition to "lifelong" and "acquired" premature ejaculation (PE) syndromes, two more PE syndromes have recently been proposed: "Natural variable PE" and "premature-like ejaculatory dysfunction." The purpose of this study was to analyze the prevalence of the four PE syndromes among patients who were admitted to a urology outpatient clinic with the complaint of ejaculating prematurely. Between July 2008 and March 2009, patients admitted to a urology outpatient clinic with a self-reported complaint of PE were enrolled into the study. After taking a careful medical and sexual history, patients were classified as "lifelong,"acquired,"natural variable," PE or "premature-like ejaculatory dysfunction." In addition to medical and sexual history, self-estimated intravaginal ejaculatory latency times (IELTs) of patients were used in the classification of patients. A total of 261 potent men with a mean age of 36.39 +/- 10.45 years (range 20-70) were recruited into the study. The majority of the men was diagnosed as having lifelong PE (62.5%); the remaining men were diagnosed as having acquired (16.1%), natural variable PE (14.5%), or premature-like ejaculatory disorder (6.9%). The mean age of patients with acquired PE was significantly higher than the other groups (P = 0.001). No significant difference was observed for educational status or income level of patients in the different PE groups (P = 0.983 and P = 0.151, respectively). The mean self-estimated IELT for all subjects was 65.16 +/- 83.75 seconds (2-420 seconds). Patients with lifelong PE had significantly lower mean self-reported IELT, whereas the patients with premature-like ejaculatory dysfunction had the highest mean IELT (P = 0.001): (i) life-long PE: 20.47 +/- 28.90 seconds (2-120 seconds); (ii) aquired PE: 57.91 +/- 38.72 seconds (90-180 seconds); (iii) natural variable PE: 144.17 +/- 22.47 seconds (120-180 seconds); and (iv) premature-like ejaculatory dysfunction: 286.67 +/- 69.96 seconds (180-420 seconds

  5. Activated human mast cells induce LOX-1-specific scavenger receptor expression in human monocyte-derived macrophages.

    Directory of Open Access Journals (Sweden)

    Mervi Alanne-Kinnunen

    Full Text Available Activated mast cells in atherosclerotic lesions degranulate and release bioactive compounds capable of regulating atherogenesis. Here we examined the ability of activated human primary mast cells to regulate the expression of the major scavenger receptors in cultured human primary monocyte-derived macrophages (HMDMs.Components released by immunologically activated human primary mast cells induced a transient expression of lectin-like oxidized LDL receptor (LOX-1 mRNA in HMDMs, while the expression of two other scavenger receptors, MSR1 and CD36, remained unaffected. The LOX-1-inducing secretory components were identified as histamine, tumor necrosis factor alpha (TNF-α, and transforming growth factor beta (TGF-β1, which exhibited a synergistic effect on LOX-1 mRNA expression. Histamine induced a transient expression of LOX-1 protein. Mast cell -induced increase in LOX-1 expression was not associated with increased uptake of oxidized LDL by the macrophages.Mast cell-derived histamine, TNF-α, and TGF-β1 act in concert to induce a transient increase in LOX-1 expression in human primary monocyte-derived macrophages. The LOX-1-inducing activity potentially endows mast cells a hitherto unrecognized role in the regulation of innate immune reactions in atherogenesis.

  6. Premature dental eruption: report of case.

    LENUS (Irish Health Repository)

    McNamara, C M

    2011-08-05

    This case report reviews the variability of dental eruption and the possible sequelae. Dental eruption of the permanent teeth in cleft palate children may be variable, with delayed eruption the most common phenomenon. A case of premature dental eruption of a maxillary left first premolar is demonstrated, however, in a five-year-old male. This localized premature dental eruption anomaly was attributed to early extraction of the primary dentition, due to caries.

  7. Adequacy of published screening criteria for retinopathy of prematurity.

    Science.gov (United States)

    Taranath, Deepa A; Oh, Dickson D-S; Keane, Miriam C; Fabel, Helen; Marshall, Peter

    2016-03-01

    Criteria for screening preterm infants for retinopathy of prematurity vary around the world. We aimed to analyse the efficacy of alternative screening criteria. We collected retrospective data at a tertiary level neonatal nursery. Our participants were 1007 babies, born between 1997 and 2011, at prematurity. We determined whether disease would be detected using an alternative Australian screening model (gestational age prematurity is our main outcome. Using several of the alternative criteria, two neonates with clinically significant retinopathy of prematurity, one of whom required laser treatment to preserve sight, would not have been screened, and their disease may have gone undetected. Use of prematurity may risk clinically significant cases being missed and others may screen babies unnecessarily. Alternative criteria should be considered and '<30 weeks gestational age and/or <1500 g birth weight' appears a viable option. © 2015 Royal Australian and New Zealand College of Ophthalmologists.

  8. Gene expression variability in human hepatic drug metabolizing enzymes and transporters.

    Directory of Open Access Journals (Sweden)

    Lun Yang

    Full Text Available Interindividual variability in the expression of drug-metabolizing enzymes and transporters (DMETs in human liver may contribute to interindividual differences in drug efficacy and adverse reactions. Published studies that analyzed variability in the expression of DMET genes were limited by sample sizes and the number of genes profiled. We systematically analyzed the expression of 374 DMETs from a microarray data set consisting of gene expression profiles derived from 427 human liver samples. The standard deviation of interindividual expression for DMET genes was much higher than that for non-DMET genes. The 20 DMET genes with the largest variability in the expression provided examples of the interindividual variation. Gene expression data were also analyzed using network analysis methods, which delineates the similarities of biological functionalities and regulation mechanisms for these highly variable DMET genes. Expression variability of human hepatic DMET genes may affect drug-gene interactions and disease susceptibility, with concomitant clinical implications.

  9. Hypoxia regulates microRNA expression in the human carotid body

    International Nuclear Information System (INIS)

    Mkrtchian, Souren; Lee, Kian Leong; Kåhlin, Jessica; Ebberyd, Anette; Poellinger, Lorenz; Fagerlund, Malin Jonsson; Eriksson, Lars I.

    2017-01-01

    The carotid body (CB) is the key sensing organ for physiological oxygen levels in the body. Under conditions of low oxygen (hypoxia), the CB plays crucial roles in signaling to the cardiorespiratory center in the medulla oblongata for the restoration of oxygen homeostasis. How hypoxia regulates gene expression in the human CB remains poorly understood. While limited information on transcriptional regulation in animal CBs is available, the identity and impact of important post-transcriptional regulators such as non-coding RNAs, and in particular miRNAs are not known. Here we show using ex vivo experiments that indeed a number of miRNAs are differentially regulated in surgically removed human CB slices when acute hypoxic conditions were applied. Analysis of the hypoxia-regulated miRNAs shows that they target biological pathways with upregulation of functions related to cell proliferation and immune response and downregulation of cell differentiation and cell death functions. Comparative analysis of the human CB miRNAome with the global miRNA expression patterns of a large number of different human tissues showed that the CB miRNAome had a unique profile which reflects its highly specialized functional status. Nevertheless, the human CB miRNAome is most closely related to the miRNA expression pattern of brain tissues indicating that they may have the most similar developmental origins. - Highlights: • Hypoxia triggers differential expression of many miRNAs in the human carotid body. • This can lead to the upregulation of proliferation and immune response functions. • CB expression profile in the carotid body resembles the miRNA expression pattern in the brain. • miRNAs are involved in the regulation of carotid body functions including oxygen sensing.

  10. Hypoxia regulates microRNA expression in the human carotid body

    Energy Technology Data Exchange (ETDEWEB)

    Mkrtchian, Souren, E-mail: souren.mkrtchian@ki.se [Section for Anesthesiology and Intensive Care Medicine, Department of Physiology and Pharmacology, Karolinska Institute, SE-171 77 Stockholm (Sweden); Lee, Kian Leong, E-mail: csilkl@nus.edu.sg [Cancer Science Institute of Singapore, National University of Singapore, 117599 Singapore (Singapore); Kåhlin, Jessica [Section for Anesthesiology and Intensive Care Medicine, Department of Physiology and Pharmacology, Karolinska Institute, SE-171 77 Stockholm (Sweden); Function Perioperative Medicine and Intensive Care, Karolinska University Hospital, SE-171 76 Stockholm (Sweden); Ebberyd, Anette [Section for Anesthesiology and Intensive Care Medicine, Department of Physiology and Pharmacology, Karolinska Institute, SE-171 77 Stockholm (Sweden); Poellinger, Lorenz [Cancer Science Institute of Singapore, National University of Singapore, 117599 Singapore (Singapore); Department of Cell and Molecular Biology, Karolinska Institute, SE-171 77 Stockholm (Sweden); Fagerlund, Malin Jonsson; Eriksson, Lars I. [Section for Anesthesiology and Intensive Care Medicine, Department of Physiology and Pharmacology, Karolinska Institute, SE-171 77 Stockholm (Sweden); Function Perioperative Medicine and Intensive Care, Karolinska University Hospital, SE-171 76 Stockholm (Sweden)

    2017-03-15

    The carotid body (CB) is the key sensing organ for physiological oxygen levels in the body. Under conditions of low oxygen (hypoxia), the CB plays crucial roles in signaling to the cardiorespiratory center in the medulla oblongata for the restoration of oxygen homeostasis. How hypoxia regulates gene expression in the human CB remains poorly understood. While limited information on transcriptional regulation in animal CBs is available, the identity and impact of important post-transcriptional regulators such as non-coding RNAs, and in particular miRNAs are not known. Here we show using ex vivo experiments that indeed a number of miRNAs are differentially regulated in surgically removed human CB slices when acute hypoxic conditions were applied. Analysis of the hypoxia-regulated miRNAs shows that they target biological pathways with upregulation of functions related to cell proliferation and immune response and downregulation of cell differentiation and cell death functions. Comparative analysis of the human CB miRNAome with the global miRNA expression patterns of a large number of different human tissues showed that the CB miRNAome had a unique profile which reflects its highly specialized functional status. Nevertheless, the human CB miRNAome is most closely related to the miRNA expression pattern of brain tissues indicating that they may have the most similar developmental origins. - Highlights: • Hypoxia triggers differential expression of many miRNAs in the human carotid body. • This can lead to the upregulation of proliferation and immune response functions. • CB expression profile in the carotid body resembles the miRNA expression pattern in the brain. • miRNAs are involved in the regulation of carotid body functions including oxygen sensing.

  11. Endothelium specific matrilysin (MMP-7) expression in human cancers

    NARCIS (Netherlands)

    Sier, C.F.M.; Hawinkels, L.J.A.C.; Zijlmans, H.J.M.A.A.; Zuidwijk, K.; Jonge de; Muller, E.S.M.; Ferreira, V.; Hanemaaijer, R.; Mulder-Stapel, A.A.; Kenter, G.G.; Verspaget, H.W.; Gorter, A.

    2008-01-01

    Over-expression of matrilysin (MMP-7) is predominantly associated with epithelial (pre)malignant cells. In the present study MMP-7 expression is also found in endothelial cells in various human cancer types. Endothelial MMP-7 was associated with CD34 and/or CD105 expression. These

  12. The predictive nature of transcript expression levels on protein expression in adult human brain.

    Science.gov (United States)

    Bauernfeind, Amy L; Babbitt, Courtney C

    2017-04-24

    Next generation sequencing methods are the gold standard for evaluating expression of the transcriptome. When determining the biological implications of such studies, the assumption is often made that transcript expression levels correspond to protein levels in a meaningful way. However, the strength of the overall correlation between transcript and protein expression is inconsistent, particularly in brain samples. Following high-throughput transcriptomic (RNA-Seq) and proteomic (liquid chromatography coupled with tandem mass spectrometry) analyses of adult human brain samples, we compared the correlation in the expression of transcripts and proteins that support various biological processes, molecular functions, and that are located in different areas of the cell. Although most categories of transcripts have extremely weak predictive value for the expression of their associated proteins (R 2 values of < 10%), transcripts coding for protein kinases and membrane-associated proteins, including those that are part of receptors or ion transporters, are among those that are most predictive of downstream protein expression levels. The predictive value of transcript expression for corresponding proteins is variable in human brain samples, reflecting the complex regulation of protein expression. However, we found that transcriptomic analyses are appropriate for assessing the expression levels of certain classes of proteins, including those that modify proteins, such as kinases and phosphatases, regulate metabolic and synaptic activity, or are associated with a cellular membrane. These findings can be used to guide the interpretation of gene expression results from primate brain samples.

  13. Variable expression of cerebral cavernous malformations in carriers of a premature termination codon in exon 17 of the Krit1 gene

    Directory of Open Access Journals (Sweden)

    Gamero Miguel A

    2003-07-01

    Full Text Available Abstract Background Cerebral cavernous malformations (CCM present as either sporadic or autosomal dominant conditions with incomplete penetrance of symptoms. Differences in genetic and environmental factors might be minimized among first-degree relatives. We therefore studied clinical expression in a family with several affected members. Methods We studied a three-generation family with the onset of CCM as a cerebral haemorrhage in the younger (four-year-old sibling. Identification and enumeration of CCMs were performed in T2-weighted or gradient-echo MRIs of the whole brains. Genetic analysis comprised SCCP, sequencing and restriction polymorphism of the Krit1 gene in the proband and at risk relatives. Results The phenotypes of cerebral cavernous malformations (CCMs in carriers of Krit1 mutations were very variable. We identified a novel frameshift mutation caused by a 1902A insertion in exon 17 of the Krit1 gene, which leads to a premature TAA triplet and predicts the truncating phenotype Y634X. A very striking finding was the absence of both clinical symptoms and CCMs in the eldest sibling harbouring the 1902insA. Conclusions Patients in this family, harbouring the same mutation, illustrate the very variable clinical and radiological expression of a Krit1 mutation. The early and critical onset in the proband contrasts with minor clinical findings in affected relatives. This consideration is important in genetic counselling.

  14. Human milk use in Australian hospitals, 1949-1985.

    Science.gov (United States)

    Thorley, Virginia

    2012-07-01

    This paper will draw mainly on the experiences of fourteen women to explore the use of expressed human milk by hospitals in Australia from the postwar period through to 1985. The purpose is to provide a snapshot of common practices before the decline of human milk banking and other uses of expressed breastmilk in Australian hospitals, thus providing a source for future comparison against the more rigorous, uniform practices being instituted in the new milk banks of the early-21st century. The ten mothers included were a convenience sample drawn from the author's networks, with recruitment continuing till a range of hospital types and a majority of states were included. Three of the mothers also had experience as trainee midwives and midwives, and four midwives contributed their experiences as staff members, only. The hospitals ranged from large teaching hospitals to small private hospitals and were in metropolitan, regional and country locations. The practices included routine expression and expression for specific purposes, whether for the mother's own baby or to donate. Some hospitals pooled the donor milk for premature or sick babies.

  15. Long-term impact of prematurity on postnatal neurohormonal regulation

    Directory of Open Access Journals (Sweden)

    M. I. Ziborova

    2016-01-01

    Full Text Available This article considers the psychophysiological and neuroendocrine differences characteristic of premature children, which are as a result of long-term perinatal consequences. Particular emphasis is laid on the effects of the hypothalamic-pituitary-adrenocortical stress system, the performance of which is reprogramed during complicated pregnancy, labor, and postnatal period under pain stress due to medical manipulations. Being extremely sensitive to all these exposures, the brain of a premature infant develops during activation of the stress system and takes on a few distinctive properties in addition to independent neuroanatomical distinctions due to premature birth. The altered neurohormonal patterns revealed in very prematurely born children and adolescents involve the regulation of mental processes, behavior, metabolism, and circadian rhythms (sleep-wake regulation, which differ from those in their maturely born peers. These cases allow learning and behavior problems and lower cognitive estimates to be considered in normally developing children born extremely prematurely who have also hormonal dysregulation.

  16. Neuromodulation of Limb Proprioceptive Afferents Decreases Apnea of Prematurity and Accompanying Intermittent Hypoxia and Bradycardia.

    Directory of Open Access Journals (Sweden)

    Kalpashri Kesavan

    Full Text Available Apnea of Prematurity (AOP is common, affecting the majority of infants born at <34 weeks gestational age. Apnea and periodic breathing are accompanied by intermittent hypoxia (IH. Animal and human studies demonstrate that IH exposure contributes to multiple pathologies, including retinopathy of prematurity (ROP, injury to sympathetic ganglia regulating cardiovascular action, impaired pancreatic islet cell and bone development, cerebellar injury, and neurodevelopmental disabilities. Current standard of care for AOP/IH includes prone positioning, positive pressure ventilation, and methylxanthine therapy; these interventions are inadequate, and not optimal for early development.The objective is to support breathing in premature infants by using a simple, non-invasive vibratory device placed over limb proprioceptor fibers, an intervention using the principle that limb movements trigger reflexive facilitation of breathing.Premature infants (23-34 wks gestational age, with clinical evidence of AOP/IH episodes were enrolled 1 week after birth. Caffeine treatment was not a reason for exclusion. Small vibration devices were placed on one hand and one foot and activated in 6 hour ON/OFF sequences for a total of 24 hours. Heart rate, respiratory rate, oxygen saturation (SpO2, and breathing pauses were continuously collected.Fewer respiratory pauses occurred during vibration periods, relative to baseline (p<0.005. Significantly fewer SpO2 declines occurred with vibration (p<0.05, relative to control periods. Significantly fewer bradycardic events occurred during vibration periods, relative to no vibration periods (p<0.05.In premature neonates, limb proprioceptive stimulation, simulating limb movement, reduces breathing pauses and IH episodes, and lowers the number of bradycardic events that accompany aberrant breathing episodes. This low-cost neuromodulatory procedure has the potential to provide a non-invasive intervention to reduce apnea, bradycardia and

  17. 'Rush' type retinopathy of prematurity: report of three cases.

    OpenAIRE

    Nissenkorn, I; Kremer, I; Gilad, E; Cohen, S; Ben-Sira, I

    1987-01-01

    Three premature infants observed to develop severe stage III retinopathy of prematurity (ROP) at 3 to 5 weeks of age received immediate treatment by cryoablation and photocoagulation, with good results. The critical importance of the ophthalmic examination of premature babies from the age of 2 weeks, so as not to overlook such cases of 'rush' type ROP is stressed and the difficulty involved in treating such small neonates is discussed.

  18. Ichthyosis prematurity syndrome: a well-defined congenital ichthyosis subtype

    DEFF Research Database (Denmark)

    Bygum, Anette; Westermark, Per; Brandrup, Flemming

    2008-01-01

    Ichthyosis prematurity syndrome is a rare syndrome characterized by the clinical triad of premature birth, thick caseous desquamating epidermis, and neonatal asphyxia. We describe two siblings with ichthyosis prematurity syndrome. The index patient was born at gestational week 34. Immediately aft...... in the stratum corneum and stratum granulosum. Diagnosing this syndrome is important to reassure parents, obstetricians, and pediatricians about its benign course after complications in the perinatal period....

  19. Retinopathy of Prematurity: Clinical Features, Classification, Natural History, Management and Outcome.

    Science.gov (United States)

    Shah, Parag K; Prabhu, Vishma; Ranjan, Ratnesh; Narendran, Venkatapathy; Kalpana, Narendran

    2016-11-07

    Retinopathy of prematurity is an avoidable cause of childhood blindness. Proper understanding of the classification and treatment methods is a must in tackling this disease. Literature search with PubMed was conducted covering the period 1940-2015 with regards to retinopathy of prematurity, retrolental fibroplasia, its natural history, classification and treatment. The clinical features, screening and staging of retinopathy of prematurity according to International classification of retinopathy of prematurity (ICROP) has been included with illustrations. The standard current treatment indications, modalities and outcomes from landmark randomized controlled trials on retinopathy of prematurity have been mentioned. This review would help pediatricians to update their current knowledge on classification and treatment of retinopathy of prematurity. Screening for retinopathy of prematurity, in India, should be performed in all preterm neonates who are born <34 weeks gestation and/or <1750 grams birthweight; as well as in babies 34-36 weeks gestation or 1750-2000 grams birthweight if they have risk factors for ROP. Screening should start by one month after birth.

  20. Premature Ejaculation and Utilization of Cognitive Techniques

    Directory of Open Access Journals (Sweden)

    Serkan AKKOYUNLU

    2013-03-01

    Full Text Available Introduction: Premature ejaculation is the most common male sexual dysfunction leading to distress in many couples. Master and Johnson emphasized the concept of early learned experiences and Kaplan emphasized lack of sensory awareness. For treatment sex therapists mainly utilize start-stop and squeeze techniques as homework. Couples enter sex therapy with some cognitive distortions and beliefs about sex and sexuality. These beliefs are also named sexual myths. For some couples using techniques to challenge cognitive distortions and maladaptive beliefs about sex and sexuality can be used. In this paper by presenting a case we discussed how cognitive techniques can be used along with behaviour techniques with couples. Case: Presenting clients are five years married couple who are thirty and twenty nine years old respectively. They attended to the outpatient clinic with the request of the female client. Their main complaint was premature ejaculation. They were diagnosed premature ejaculation using clinical interview. In treatment besides start and stop technique, cognitive techniques were utilized to address dysfunctional beliefs about sexuality. Discussion: Premature ejaculation is a male sexual dysfunction that causes distress and intimacy problems between couples. Stop start and squeeze techniques were accepted as the choice of treatment but their effectiveness is questioned recently. Also cognitive distortions and maladaptive beliefs may hamper therapy progress. Besides that, behavioral techniques utilizing cognitive techniques to lessen the degree of dysfunctional beliefs about sex and sexuality may help the couple to overcome premature ejaculation and enhance sexual satisfaction and intimacy.

  1. Expression of human lymphotoxin alpha in Aspergillus niger

    NARCIS (Netherlands)

    Krasevec, N.; Hondel, C.A.M.J.J. van de; Komel, R.

    2000-01-01

    A gene-fusion expression strategy was applied for heterologous expression of human lymphotoxin alpha (LTα) in the Aspergillus niger AB1.13 protease-deficient strain. The LTα gene was fused with the A. niger glucoamylase GII-form as a carrier-gene, behind its transcription control and secretion

  2. Melatonin and Fertoprotective Adjuvants: Prevention against Premature Ovarian Failure during Chemotherapy.

    Science.gov (United States)

    Jang, Hoon; Hong, Kwonho; Choi, Youngsok

    2017-06-07

    Premature ovarian failure is one of the side effects of chemotherapy in pre-menopausal cancer patients. Preservation of fertility has become increasingly important in improving the quality of life of completely recovered cancer patients. Among the possible strategies for preserving fertility such as ovarian tissue cryopreservation, co-treatment with a pharmacological adjuvant is highly effective and poses less of a burden on the human body. Melatonin is generally produced in various tissues and acts as a universally acting antioxidant in cells. Melatonin is now more widely used in various biological processes including treating insomnia and an adjuvant during chemotherapy. In this review, we summarize the information indicating that melatonin may be useful for reducing and preventing premature ovarian failure in chemotherapy-treated female patients. We also mention that many adjuvants other than melatonin are developed and used to inhibit chemotherapy-induced infertility. This information will give us novel insights on the clinical use of melatonin and other agents as fertoprotective adjuvants for female cancer patients.

  3. LINE FUSION GENES: a database of LINE expression in human genes

    Directory of Open Access Journals (Sweden)

    Park Hong-Seog

    2006-06-01

    Full Text Available Abstract Background Long Interspersed Nuclear Elements (LINEs are the most abundant retrotransposons in humans. About 79% of human genes are estimated to contain at least one segment of LINE per transcription unit. Recent studies have shown that LINE elements can affect protein sequences, splicing patterns and expression of human genes. Description We have developed a database, LINE FUSION GENES, for elucidating LINE expression throughout the human gene database. We searched the 28,171 genes listed in the NCBI database for LINE elements and analyzed their structures and expression patterns. The results show that the mRNA sequences of 1,329 genes were affected by LINE expression. The LINE expression types were classified on the basis of LINEs in the 5' UTR, exon or 3' UTR sequences of the mRNAs. Our database provides further information, such as the tissue distribution and chromosomal location of the genes, and the domain structure that is changed by LINE integration. We have linked all the accession numbers to the NCBI data bank to provide mRNA sequences for subsequent users. Conclusion We believe that our work will interest genome scientists and might help them to gain insight into the implications of LINE expression for human evolution and disease. Availability http://www.primate.or.kr/line

  4. Premature rupture of membranes

    Science.gov (United States)

    ... gov/ency/patientinstructions/000512.htm Premature rupture of membranes To use the sharing features on this page, ... water that surrounds your baby in the womb. Membranes or layers of tissue hold in this fluid. ...

  5. CHARACTERIZATION OF THE OLFACTORY RECEPTORS EXPRESSED IN HUMAN SPERMATOZOA

    Directory of Open Access Journals (Sweden)

    Caroline eFlegel

    2016-01-01

    Full Text Available The detection of external cues is fundamental for human spermatozoa to locate the oocyte in the female reproductive tract. This task requires a specific chemoreceptor repertoire that is expressed on the surface of human spermatozoa, which is not fully identified to date. Olfactory receptors (ORs are candidate molecules and have been attributed to be involved in sperm chemotaxis and chemokinesis, indicating an important role in mammalian spermatozoa. An increasing importance has been suggested for spermatozoal RNA, which led us to investigate the expression of all 387 OR genes. This study provides the first comprehensive analysis of OR transcripts in human spermatozoa of several individuals by RNA-Seq. We detected 91 different transcripts in the spermatozoa samples that could be aligned to annotated OR genes. Using stranded mRNA-Seq, we detected a class of these putative OR transcripts in an antisense orientation, indicating a different function, rather than coding for a functional OR protein. Nevertheless, we were able to detect OR proteins in various compartments of human spermatozoa, indicating distinct functions in human sperm. A panel of various OR ligands induced Ca2+ signals in human spermatozoa, which could be inhibited by mibefradil. This study indicated that a variety of ORs are expressed at the mRNA and protein level in human spermatozoa and demonstrates that ORs are involved in the physiological processes.

  6. L-Dopa decarboxylase expression profile in human cancer cells.

    Science.gov (United States)

    Chalatsa, Ioanna; Nikolouzou, Eleftheria; Fragoulis, Emmanuel G; Vassilacopoulou, Dido

    2011-02-01

    L-Dopa decarboxylase (DDC) catalyses the decarboxylation of L-Dopa. It has been shown that the DDC gene undergoes alternative splicing within its 5'-untranslated region (UTR), in a tissue-specific manner, generating identical protein products. The employment of two alternative 5'UTRs is thought to be responsible for tissue-specific expression of the human DDC mRNA. In this study, we focused on the investigation of the nature of the mRNA expression in human cell lines of neural and non-neural origin. Our results show the expression of a neural-type DDC mRNA splice variant, lacking exon 3 in all cell lines studied. Co-expression of the full length non-neural DDC mRNA and the neural-type DDC splice variant lacking exon 3 was detected in all cell lines. The alternative DDC protein isoform, Alt-DDC, was detected in SH-SY5Y and HeLa cells. Our findings suggest that the human DDC gene undergoes complex processing, leading to the formation of multiple mRNA isoforms. The study of the significance of this phenomenon of multiple DDC mRNA isoforms could provide us with new information leading to the elucidation of the complex biological pathways that the human enzyme is involved in.

  7. Decoding NADPH oxidase 4 expression in human tumors

    Directory of Open Access Journals (Sweden)

    Jennifer L. Meitzler

    2017-10-01

    Full Text Available NADPH oxidase 4 (NOX4 is a redox active, membrane-associated protein that contributes to genomic instability, redox signaling, and radiation sensitivity in human cancers based on its capacity to generate H2O2 constitutively. Most studies of NOX4 in malignancy have focused on the evaluation of a small number of tumor cell lines and not on human tumor specimens themselves; furthermore, these studies have often employed immunological tools that have not been well characterized. To determine the prevalence of NOX4 expression across a broad range of solid tumors, we developed a novel monoclonal antibody that recognizes a specific extracellular region of the human NOX4 protein, and that does not cross-react with any of the other six members of the NOX gene family. Evaluation of 20 sets of epithelial tumors revealed, for the first time, high levels of NOX4 expression in carcinomas of the head and neck (15/19 patients, esophagus (12/18 patients, bladder (10/19 patients, ovary (6/17 patients, and prostate (7/19 patients, as well as malignant melanoma (7/15 patients when these tumors were compared to histologically-uninvolved specimens from the same organs. Detection of NOX4 protein upregulation by low levels of TGF-β1 demonstrated the sensitivity of this new probe; and immunofluorescence experiments found that high levels of endogenous NOX4 expression in ovarian cancer cells were only demonstrable associated with perinuclear membranes. These studies suggest that NOX4 expression is upregulated, compared to normal tissues, in a well-defined, and specific group of human carcinomas, and that its expression is localized on intracellular membranes in a fashion that could modulate oxidative DNA damage.

  8. The relationship of the subtypes of preterm birth with retinopathy of prematurity.

    Science.gov (United States)

    Lynch, Anne M; Wagner, Brandie D; Hodges, Jennifer K; Thevarajah, Tamara S; McCourt, Emily A; Cerda, Ashlee M; Mandava, Naresh; Gibbs, Ronald S; Palestine, Alan G

    2017-09-01

    Retinopathy of prematurity is an adverse outcome of preterm birth and is a leading cause of childhood blindness. The relationship between the subtypes of preterm birth with retinopathy of prematurity is understudied. To investigate whether there is a difference in the incidence of type 1 or type 2 retinopathy of prematurity in infants with preterm birth resulting from spontaneous preterm labor, a medical indication of preterm birth, or preterm premature rupture of the membranes. A retrospective cohort study was conducted of 827 infants screened for retinopathy of prematurity who were delivered at a single tertiary care center in Colorado. All infants fulfilled the American Academy of Pediatrics 2013 screening criteria for retinopathy of prematurity defined as "infants with a birth weight of ≤1500 g or gestational age of 30 weeks or less (as defined by the attending neonatologist) and selected infants with a birth weight between 1500 and 2000 g or gestational age of >30 weeks with an unstable clinical course, including those requiring cardiorespiratory support and who are believed by their attending pediatrician or neonatologist to be at high risk for retinopathy of prematurity." Two independent reviewers masked to retinopathy of prematurity outcomes determined whether preterm birth resulted from spontaneous preterm labor, medical indication of preterm birth, or preterm premature rupture of the membranes. Discrepancies were resolved by a third reviewer. Data were analyzed with univariate and multivariable logistic regression. In our cohort, the frequency of preterm birth resulting from spontaneous preterm labor, medical indication of preterm birth, or preterm premature rupture of the membranes was 34%, 40%, and 26%, respectively. The mean gestational age (weeks, days) ± SD (range) in the cohort and across the preterm birth subtypes was as follows: entire cohort, 28 weeks, 6 days ± 2 weeks, 3 days (23 weeks, 3 days - 36 weeks, 4 days); spontaneous preterm labor

  9. A dose-effect curve of premature condensation chromosome ring in lymphocytes of human peripheral blood exposed to high dose of 60Co γ-rays in vitro

    International Nuclear Information System (INIS)

    Yao Bo; Li Yufang; Liu Guangxian; Huang Shan; Jiang Benrong; Ai Huisheng

    2009-01-01

    Objective: To establish a dose-effect curve of premature condensation chromosome ring (PCC-R) in lymphocytes of human peripheral blood after exposed to high doses of γ-rays. Methods: Peripheral blood samples was drawn from three healthy individuals, and exposed to 60 Co γ-rays with doses between 0 and 30 Gy. The frequencies of PCC-R in premature condensation chromosome (PCC) cells obtained by Okadaic acid (OA) induction were calculated, and a dose-effect curve was fitted. Results: PCC index tapered with dose. Frequencies of PCC-R per cell increased until 20 Gy, and then saturation was observed. The results were fitted to a lineal model up to 20 Gy: y=-0.020 + 0.052D, where y was the frequencies of PCC-R per cell, D was the radiation dose(Gy). Conclusions: The highest dose could be estimated is 20 Gy by the dose-effect curve established with PCC-R method. Its utility and validity will be verified in the future application of radiation accident. (authors)

  10. Nutritional factors and visual function in premature infants.

    Science.gov (United States)

    Jewell, V C; Northrop-Clewes, C A; Tubman, R; Thurnham, D I

    2001-05-01

    Approximately 5-7% of all infants are born prematurely, and birth before 37 weeks is the most common cause of neonatal mortality, morbidity and long-term disability. Premature infants are poorly equipped for life outside the womb, and oxidant stress has been implicated in the aetiology of visual impairment in these infants, who are often exposed to increased O2 concentrations and high light intensity in neonatal units. The carotenoids lutein and zeaxanthin, which give the macular area of the eye its yellow colour, are located in the retinal pigment epithelium of the eye, and are believed to play a role in protecting it against oxidative and light damage. The macular pigments are of dietary origin, and green leafy vegetables are the primary source of lutein and zeaxanthin. Lutein is one of the five most common carotenoids found in the diet. There is current interest in the macular pigment in relation to age-related macular degeneration, but these pigments may also have a protective role in the retinal pigment epithelium of the newborn infant. Little information is available on blood lutein and zeaxanthin levels in neonates. Levels of lutein in human milk are two to three times higher than those of beta-carotene, whereas their concentrations in the mothers' blood are approximately the same. Human milk is the main dietary source of lutein and zeaxanthin for infants until weaning occurs. The biochemical mechanisms which mediate the transport of the macular carotenoids into the eye are not known, but tubulin has been identified as the major carotenoid-binding protein, and may play a role in the physiology of the macula.

  11. Retinopathy of prematurity - from recognition of risk factors to treatment recommendations.

    Science.gov (United States)

    Fagerholm, Reija; Vesti, Eija

    Retinopathy of prematurity is a proliferative retinal disorder diagnosed exclusively in prematurely born infants. In retinopathy of prematurity, growth of the retinal vasculature is disturbed, leading to hypoxia-induced pathological changes typical of retinopathy of prematurity, in the worst case resulting in retinal detachment. The most typical risk factors predisposing to the disease include hyperoxemia, low levels of insulin-like growth factor 1 (IGF-I), and low birth weight in relation to weeks of pregnancy. Laser therapy of peripheral retina is the currently established form of treatment. Screening is applied in order to recognize the pathological changes in retinopathy of prematurity early enough.

  12. Dogs can discriminate human smiling faces from blank expressions.

    Science.gov (United States)

    Nagasawa, Miho; Murai, Kensuke; Mogi, Kazutaka; Kikusui, Takefumi

    2011-07-01

    Dogs have a unique ability to understand visual cues from humans. We investigated whether dogs can discriminate between human facial expressions. Photographs of human faces were used to test nine pet dogs in two-choice discrimination tasks. The training phases involved each dog learning to discriminate between a set of photographs of their owner's smiling and blank face. Of the nine dogs, five fulfilled these criteria and were selected for test sessions. In the test phase, 10 sets of photographs of the owner's smiling and blank face, which had previously not been seen by the dog, were presented. The dogs selected the owner's smiling face significantly more often than expected by chance. In subsequent tests, 10 sets of smiling and blank face photographs of 20 persons unfamiliar to the dogs were presented (10 males and 10 females). There was no statistical difference between the accuracy in the case of the owners and that in the case of unfamiliar persons with the same gender as the owner. However, the accuracy was significantly lower in the case of unfamiliar persons of the opposite gender to that of the owner, than with the owners themselves. These results suggest that dogs can learn to discriminate human smiling faces from blank faces by looking at photographs. Although it remains unclear whether dogs have human-like systems for visual processing of human facial expressions, the ability to learn to discriminate human facial expressions may have helped dogs adapt to human society.

  13. Premature graying of hair: An independent risk marker for coronary ...

    African Journals Online (AJOL)

    The presence of premature graying of hair was associated with 3.24 times the risk of CAD on multiple logistic regression analysis. CONCLUSION: The presence of premature graying of hair was associated with an increased risk of CAD in young smokers. Premature graying of hair can be used as preliminary evidence by ...

  14. Hepatocyte specific expression of human cloned genes

    Energy Technology Data Exchange (ETDEWEB)

    Cortese, R

    1986-01-01

    A large number of proteins are specifically synthesized in the hepatocyte. Only the adult liver expresses the complete repertoire of functions which are required at various stages during development. There is therefore a complex series of regulatory mechanisms responsible for the maintenance of the differentiated state and for the developmental and physiological variations in the pattern of gene expression. Human hepatoma cell lines HepG2 and Hep3B display a pattern of gene expression similar to adult and fetal liver, respectively; in contrast, cultured fibroblasts or HeLa cells do not express most of the liver specific genes. They have used these cell lines for transfection experiments with cloned human liver specific genes. DNA segments coding for alpha1-antitrypsin and retinol binding protein (two proteins synthesized both in fetal and adult liver) are expressed in the hepatoma cell lines HepG2 and Hep3B, but not in HeLa cells or fibroblasts. A DNA segment coding for haptoglobin (a protein synthesized only after birth) is only expressed in the hepatoma cell line HepG2 but not in Hep3B nor in non hepatic cell lines. The information for tissue specific expression is located in the 5' flanking region of all three genes. In vivo competition experiments show that these DNA segments bind to a common, apparently limiting, transacting factor. Conventional techniques (Bal deletions, site directed mutagenesis, etc.) have been used to precisely identify the DNA sequences responsible for these effects. The emerging picture is complex: they have identified multiple, separate transcriptional signals, essential for maximal promoter activation and tissue specific expression. Some of these signals show a negative effect on transcription in fibroblast cell lines.

  15. Neighborhood Environmental Health and Premature Death From Cardiovascular Disease.

    Science.gov (United States)

    Gaglioti, Anne H; Xu, Junjun; Rollins, Latrice; Baltrus, Peter; O'Connell, Laura Kathryn; Cooper, Dexter L; Hopkins, Jammie; Botchwey, Nisha D; Akintobi, Tabia Henry

    2018-02-01

    Cardiovascular disease (CVD) is the leading cause of death in the United States and disproportionately affects racial/ethnic minority groups. Healthy neighborhood conditions are associated with increased uptake of health behaviors that reduce CVD risk, but minority neighborhoods often have poor food access and poor walkability. This study tested the community-driven hypothesis that poor access to food at the neighborhood level and poor neighborhood walkability are associated with racial disparities in premature deaths from CVD. We examined the relationship between neighborhood-level food access and walkability on premature CVD mortality rates at the census tract level for the city of Atlanta using multivariable logistic regression models. We produced maps to illustrate premature CVD mortality, food access, and walkability by census tract for the city. We found significant racial differences in premature CVD mortality rates and geographic disparities in food access and walkability among census tracts in Atlanta. Improved food access and walkability were associated with reduced overall premature CVD mortality in unadjusted models, but this association did not persist in models adjusted for census tract population composition and poverty. Census tracts with high concentrations of minority populations had higher levels of poor food access, poor walkability, and premature CVD mortality. This study highlights disparities in premature CVD mortality and neighborhood food access and walkability at the census tract level in the city of Atlanta. Improving food access may have differential effects for subpopulations living in the same area. These results can be used to calibrate neighborhood-level interventions, and they highlight the need to examine race-specific health outcomes.

  16. Identification of differentially expressed microRNAs in human male breast cancer

    Directory of Open Access Journals (Sweden)

    Schipper Elisa

    2010-03-01

    Full Text Available Abstract Background The discovery of small non-coding RNAs and the subsequent analysis of microRNA expression patterns in human cancer specimens have provided completely new insights into cancer biology. Genetic and epigenetic data indicate oncogenic or tumor suppressor function of these pleiotropic regulators. Therefore, many studies analyzed the expression and function of microRNA in human breast cancer, the most frequent malignancy in females. However, nothing is known so far about microRNA expression in male breast cancer, accounting for approximately 1% of all breast cancer cases. Methods The expression of 319 microRNAs was analyzed in 9 primary human male breast tumors and in epithelial cells from 15 male gynecomastia specimens using fluorescence-labeled bead technology. For identification of differentially expressed microRNAs data were analyzed by cluster analysis and selected statistical methods. Expression levels were validated for the most up- or down-regulated microRNAs in this training cohort using real-time PCR methodology as well as in an independent test cohort comprising 12 cases of human male breast cancer. Results Unsupervised cluster analysis separated very well male breast cancer samples and control specimens according to their microRNA expression pattern indicating cancer-specific alterations of microRNA expression in human male breast cancer. miR-21, miR519d, miR-183, miR-197, and miR-493-5p were identified as most prominently up-regulated, miR-145 and miR-497 as most prominently down-regulated in male breast cancer. Conclusions Male breast cancer displays several differentially expressed microRNAs. Not all of them are shared with breast cancer biopsies from female patients indicating male breast cancer specific alterations of microRNA expression.

  17. Acetaminophen developmental pharmacokinetics in premature neonates and infants

    DEFF Research Database (Denmark)

    Anderson, Brian J; van Lingen, Richard A; Hansen, Tom G

    2002-01-01

    The aim of this study was to describe acetaminophen developmental pharmacokinetics in premature neonates through infancy to suggest age-appropriate dosing regimens.......The aim of this study was to describe acetaminophen developmental pharmacokinetics in premature neonates through infancy to suggest age-appropriate dosing regimens....

  18. Retinopathy of Prematurity (ROP)

    Science.gov (United States)

    ... developing severe ROP, especially those in underserved or remote areas. Currently in the U.S., evaluation of premature ... files require the free Adobe® Reader® software for viewing. This website is maintained by the NEI Office ...

  19. Retinopathy of prematurity in a cohort of neonates at Groote Schuur ...

    African Journals Online (AJOL)

    Retinopathy of prematurity (ROP) is a preventable cause of visual impairment in premature ... and extremely low-birth-weight (ELBW) premature infants from the West Metro ...... Arch Ophthalmol 2000;118(5):645-649. http://dx.doi.org/10.1001/.

  20. Computed tomography of the head of new born premature infants

    International Nuclear Information System (INIS)

    Ohno, Tsutomu; Mizobe, Naoki; Takehiro, Hideo

    1983-01-01

    Evaluation of the extracerebral space on CT resulted as follows: The existence of the etracerebral space in the parieto-occipital region (PO-ECS) was physiological findings characteristic to premature infants. Its incidence was higher and the width of the space was greater, in those of premature infants. Generally PO-ECS disappeared around 40 weeks of gestation, while it tended to remaine beyond 40 weeks in premature infants born after less than 30 weeks of pregnancy. The appearance and disappearance of the PO-ECS may present some approach to learning the development of the brain in premature infants. (Ueda, J.)

  1. The economic impact of prematurity and bronchopulmonary dysplasia.

    Science.gov (United States)

    Álvarez-Fuente, María; Arruza, Luis; Muro, Marta; Zozaya, Carlos; Avila, Alejandro; López-Ortego, Paloma; González-Armengod, Carmen; Torrent, Alba; Gavilán, Jose Luis; Del Cerro, María Jesús

    2017-12-01

    Bronchopulmonary dysplasia (BPD) is one of the most serious chronic lung diseases in infancy and one of the most important sequels of premature birth (prevalence of 15-50%). Our objective was to estimate the cost of BPD of one preterm baby, with no other major prematurity-related complications, during the first 2 years of life in Spain. Data from the Spanish Ministry of Health regarding costs of diagnosis-related group of preterm birth, hospital admissions and visits, palivizumab administration, and oxygen therapy in the year 2013 were analyzed. In 2013, 2628 preterm babies were born with a weight under 1500 g; 50.9% were males. The need for respiratory support was 2.5% needed only oxygen therapy, 39.5% required conventional mechanical ventilation, and 14.9% required high-frequency ventilation. The incidence of BPD was of 34.9%. The cost of the first 2 years of life of a preterm baby with BPD and no other major prematurity-related complications ranged between 45,049.81 € and 118,760.43 €, in Spain, depending on birth weight and gestational age. If the baby required home oxygen therapy or developed pulmonary hypertension, this cost could add up to 181,742.43 €. Prematurity and BPD have an elevated cost, even for public health care systems. This cost will probably increase in the coming years if the incidence and survival of preterm babies keeps rising. The development of new therapies and preventive strategies to decrease the incidence of BPD and other morbidities associated with prematurity should be a priority. What is known: • Bronchopulmonary dysplasia (BPD) is a serious chronic lung disease related with premature birth. • BPD is an increasing disease due to the up-rise in the number of premature births. What is new: • The economic cost of preterm birth and BPD has never before been estimated in Spain nor published with European data. • Preterm babies with BPD and a good clinical outcome carry also an important economic and social burden.

  2. RESEARCH ON REDUCING PREMATURITY RUPTURE OF MEMBRANE

    Directory of Open Access Journals (Sweden)

    Maria URSACHI (BOLOTA

    2016-12-01

    Full Text Available The membranes surrounding the amniotic cavity are composed from amnion and chorion, tightly adherent layers which are composed of several cell types, including epithelial cells, trophoblasts cells and mesenchyme cells, embedded in a collagenous matrix. They retain amniotic fluid, secret substances into the amniotic fluid, as well as to the uterus and protect the fetus against upward infections from urogenital tract. Normally, the membranes it breaks during labor. Premature rupture of the amniotic sac (PRAS is defined as rupture of membranes before the onset of labor. Premature rupture of the fetal membrane, which occurs before 37 weeks of gestation, usually, refers to preterm premature rupture of membranes. Despite advances in the care period, premature rupture of membranes and premature rupture of membranes preterm continue to be regarded as serious obstetric complications. On the term 8% - 10% of pregnant women have premature rupture of membranes; these women are at increased risk of intrauterine infections, where the interval between membrane rupture and expulsion is rolled-over. Premature rupture of membranes preterm occurs in approximately 1% of all pregnancies and is associated with 30% -40% of preterm births. Thus, it is important to identify the cause of pre-term birth (after less than 37 completed weeks of "gestation" and its complications, including respiratory distress syndrome, neonatal infection and intraventricular hemorrhage. Objectives: the development of the protocol of the clinical trial on patients with impending preterm birth, study clinical and statistical on the socio-demographic characteristics of patients with imminent preterm birth; clinical condition of patients and selection of cases that could benefit from the application of interventional therapy; preclinical investigation (biological and imaging of patients with imminent preterm birth; the modality therapy; clinical investigation of the effectiveness of short

  3. Age-Related Effect of Viral-Induced Wheezing in Severe Prematurity

    Directory of Open Access Journals (Sweden)

    Geovanny F. Perez

    2016-10-01

    Full Text Available Premature children are prone to severe viral respiratory infections in early life, but the age at which susceptibility peaks and disappears for each pathogen is unclear. Methods: A retrospective analysis was performed of the age distribution and clinical features of acute viral respiratory infections in full-term and premature children, aged zero to seven years. Results: The study comprised of a total of 630 hospitalizations (n = 580 children. Sixty-seven percent of these hospitalizations occurred in children born full-term (>37 weeks, 12% in preterm (32–37 weeks and 21% in severely premature children (<32 weeks. The most common viruses identified were rhinovirus (RV; 60% and respiratory syncytial virus (RSV; 17%. Age-distribution analysis of each virus identified that severely premature children had a higher relative frequency of RV and RSV in their first three years, relative to preterm or full-term children. Additionally, the probability of RV- or RSV-induced wheezing was higher overall in severely premature children less than three years old. Conclusions: Our results indicate that the vulnerability to viral infections in children born severely premature is more specific for RV and RSV and persists during the first three years of age. Further studies are needed to elucidate the age-dependent molecular mechanisms that underlie why premature infants develop RV- and RSV-induced wheezing in early life.

  4. Gene Expression Analysis to Assess the Relevance of Rodent Models to Human Lung Injury.

    Science.gov (United States)

    Sweeney, Timothy E; Lofgren, Shane; Khatri, Purvesh; Rogers, Angela J

    2017-08-01

    The relevance of animal models to human diseases is an area of intense scientific debate. The degree to which mouse models of lung injury recapitulate human lung injury has never been assessed. Integrating data from both human and animal expression studies allows for increased statistical power and identification of conserved differential gene expression across organisms and conditions. We sought comprehensive integration of gene expression data in experimental acute lung injury (ALI) in rodents compared with humans. We performed two separate gene expression multicohort analyses to determine differential gene expression in experimental animal and human lung injury. We used correlational and pathway analyses combined with external in vitro gene expression data to identify both potential drivers of underlying inflammation and therapeutic drug candidates. We identified 21 animal lung tissue datasets and three human lung injury bronchoalveolar lavage datasets. We show that the metasignatures of animal and human experimental ALI are significantly correlated despite these widely varying experimental conditions. The gene expression changes among mice and rats across diverse injury models (ozone, ventilator-induced lung injury, LPS) are significantly correlated with human models of lung injury (Pearson r = 0.33-0.45, P human lung injury. Predicted therapeutic targets, peptide ligand signatures, and pathway analyses are also all highly overlapping. Gene expression changes are similar in animal and human experimental ALI, and provide several physiologic and therapeutic insights to the disease.

  5. Neighborhood Environmental Health and Premature Death From Cardiovascular Disease

    Science.gov (United States)

    Xu, Junjun; Rollins, Latrice; Baltrus, Peter; O’Connell, Laura Kathryn; Cooper, Dexter L.; Hopkins, Jammie; Botchwey, Nisha D.; Akintobi, Tabia Henry

    2018-01-01

    Introduction Cardiovascular disease (CVD) is the leading cause of death in the United States and disproportionately affects racial/ethnic minority groups. Healthy neighborhood conditions are associated with increased uptake of health behaviors that reduce CVD risk, but minority neighborhoods often have poor food access and poor walkability. This study tested the community-driven hypothesis that poor access to food at the neighborhood level and poor neighborhood walkability are associated with racial disparities in premature deaths from CVD. Methods We examined the relationship between neighborhood-level food access and walkability on premature CVD mortality rates at the census tract level for the city of Atlanta using multivariable logistic regression models. We produced maps to illustrate premature CVD mortality, food access, and walkability by census tract for the city. Results We found significant racial differences in premature CVD mortality rates and geographic disparities in food access and walkability among census tracts in Atlanta. Improved food access and walkability were associated with reduced overall premature CVD mortality in unadjusted models, but this association did not persist in models adjusted for census tract population composition and poverty. Census tracts with high concentrations of minority populations had higher levels of poor food access, poor walkability, and premature CVD mortality. Conclusion This study highlights disparities in premature CVD mortality and neighborhood food access and walkability at the census tract level in the city of Atlanta. Improving food access may have differential effects for subpopulations living in the same area. These results can be used to calibrate neighborhood-level interventions, and they highlight the need to examine race-specific health outcomes. PMID:29389312

  6. The relation between oxygen saturation level and retionopathy of prematurity

    Directory of Open Access Journals (Sweden)

    Mohammad Gharavi Fard

    2016-03-01

    Full Text Available Introduction: Oxygen therapy used for preterm infant disease might be associated with oxygen toxicity or oxidative stress. The exact oxygen concentration to control and maintain the arterial oxygen saturation balance is not certainly clear. We aimed to compare the efficacy of higher or lower oxygen saturations on the development of severe retinopathy of prematurity which is a major cause of blindness in preterm neonates. Methods: PubMed was searched for obtaining the relevant articles. A total of seven articles were included after studying the titles, abstracts, and the full text of retrieved articles at initial search. Inclusion criteria were all the English language human clinical randomized controlled trials with no time limitation, which studied the efficacy of low versus high oxygen saturation measured by pulse oximetry in preterm infants.Result: It can be suggested that lower limits of oxygen saturations have higher efficacy at postmesetural age of ≤28 weeks in preterm neonates. This relation has been demonstrated in five large clinical trials including three Boost trials, COT, and Support.Discussion: Applying higher concentrations of oxygen supplementations at mesentural age ≥32 weeks reduced the development of retinopathy of prematurity. Lower concentrations of oxygen saturation decreased the incidence and the development of retinopathy of prematurity in preterm neonates while applied soon after the birth.Conclusions: Targeting levels of oxygen saturation in the low or high range should be performed cautiously with attention to the postmesentural age in preterm infants at the time of starting the procedures.

  7. Gene expression in the aging human brain: an overview.

    Science.gov (United States)

    Mohan, Adith; Mather, Karen A; Thalamuthu, Anbupalam; Baune, Bernhard T; Sachdev, Perminder S

    2016-03-01

    The review aims to provide a summary of recent developments in the study of gene expression in the aging human brain. Profiling differentially expressed genes or 'transcripts' in the human brain over the course of normal aging has provided valuable insights into the biological pathways that appear activated or suppressed in late life. Genes mediating neuroinflammation and immune system activation in particular, show significant age-related upregulation creating a state of vulnerability to neurodegenerative and neuropsychiatric disease in the aging brain. Cellular ionic dyshomeostasis and age-related decline in a host of molecular influences on synaptic efficacy may underlie neurocognitive decline in later life. Critically, these investigations have also shed light on the mobilization of protective genetic responses within the aging human brain that help determine health and disease trajectories in older age. There is growing interest in the study of pre and posttranscriptional regulators of gene expression, and the role of noncoding RNAs in particular, as mediators of the phenotypic diversity that characterizes human brain aging. Gene expression studies in healthy brain aging offer an opportunity to unravel the intricately regulated cellular underpinnings of neurocognitive aging as well as disease risk and resiliency in late life. In doing so, new avenues for early intervention in age-related neurodegenerative disease could be investigated with potentially significant implications for the development of disease-modifying therapies.

  8. Role of stress peptides during human pregnancy and labour.

    Science.gov (United States)

    Hillhouse, Edward W; Grammatopoulos, Dimitris K

    2002-09-01

    Premature birth is the major source of perinatal death and disability. Furthermore, the intrauterine health of the baby is important for preventing certain adult diseases. However, the molecular mechanisms driving the onset of human labour remain uncertain, although several key players have been identified. It is becoming clear that there are many pathways to parturition in humans. Stress peptides, in particular placental corticotrophin releasing hormone (CRH) and possibly the related peptide urocortin, appear to play important roles throughout pregnancy. Plasma CRH is a predictor of the duration of human gestation. During most of pregnancy, CRH, acting via specific CRH receptor subtypes, plays a 'protective' role by promoting myometrial quiescence via the generation of cAMP and cGMP, and upregulation of nitric oxide synthase expression. At term, myometrial contractility is enhanced by a complex series of molecular switches, involving the upregulation of oxytocin receptor expression and crosstalk between the oxytocin and CRH receptors. This results in protein kinase C-induced phosphorylation of specific CRH receptor subtypes, with subsequent desensitization and a shift in the intracellular microenvironment to enhance contractility. CRH/urocortin, via specific receptor isoforms, is now able to activate Gq and potentially enhance the oxytocin-driven generation of inositol triphosphate. In addition, CRH/urocortin, via specific CRH receptor subtypes, may generate prostaglandins from the fetal membranes and decidua, play a role in placental vasodilatation and participate in fetal adrenal function and organ maturation. These peptides and receptors are phylogenetically ancient and well preserved across species. They may have evolved as a mechanism to protect against the 'stress' of premature birth.

  9. [Development and evaluation of an e-learning program for mothers of premature infants].

    Science.gov (United States)

    Lee, Nae-Young; Kim, Young-Hae

    2008-02-01

    It has been attempted to support mother of premature infants by providing information of premature infant care using e-learning because premature infants need continuous care from birth to after discharge. The e-Learning Program for mother of premature was developed with Xpert, Namo web editor, Adobe Photoshop, and PowerPoint and applied for 4 weeks from 4 to 30 September 2006. 1) We found that the contents of information which premature infants' need when being in the hospital and after discharge were the definition of a premature infant, orientation of NICU, care of premature infants, care of premature infants' common diseases, the connection of healthcare resources, exchange of information, and the management of rearing stress. 2) The program content consisted of cause of premature birth, comparison to full-term baby, physiology character, orientation of NICU, common health problems, follow up care, infection control, feeding, normal development physically and mentally, weaning method, and vaccination. Considering the results, this program for mother of premature is a useful means to provide premature-care information to mothers. This information can be readily accessible and can be varied and complex enough to be able to help mothers to the information and assistance they require.

  10. VEGF-mediated angiogenesis stimulates neural stem cell proliferation and differentiation in the premature brain

    International Nuclear Information System (INIS)

    Sun, Jinqiao; Sha, Bin; Zhou, Wenhao; Yang, Yi

    2010-01-01

    This study investigated the effects of angiogenesis on the proliferation and differentiation of neural stem cells in the premature brain. We observed the changes in neurogenesis that followed the stimulation and inhibition of angiogenesis by altering vascular endothelial growth factor (VEGF) expression in a 3-day-old rat model. VEGF expression was overexpressed by adenovirus transfection and down-regulated by siRNA interference. Using immunofluorescence assays, Western blot analysis, and real-time PCR methods, we observed angiogenesis and the proliferation and differentiation of neural stem cells. Immunofluorescence assays showed that the number of vWF-positive areas peaked at day 7, and they were highest in the VEGF up-regulation group and lowest in the VEGF down-regulation group at every time point. The number of neural stem cells, neurons, astrocytes, and oligodendrocytes in the subventricular zone gradually increased over time in the VEGF up-regulation group. Among the three groups, the number of these cells was highest in the VEGF up-regulation group and lowest in the VEGF down-regulation group at the same time point. Western blot analysis and real-time PCR confirmed these results. These data suggest that angiogenesis may stimulate the proliferation of neural stem cells and differentiation into neurons, astrocytes, and oligodendrocytes in the premature brain.

  11. [Evaluation of maternal parameters as risk factors for premature birth (individual and combined effects)].

    Science.gov (United States)

    Voigt, M; Briese, V; Pietzner, V; Kirchengast, S; Schneider, K T M; Straube, S; Jorch, G

    2009-08-01

    We aimed to examine the individual and combined effects of nine maternal parameters (biological, medical, and social) on rates of prematurity. Our objective was to provide obstetricians with a way of screening women for likely premature deliveries. We conducted a retrospective analysis on the data of about 2.3 million pregnancies taken from the German perinatal statistics of 1995-2000. Rates of prematurity were calculated with single and multi-dimensional analyses on the basis of nine maternal parameters (age, weight, height, number of previous live births, stillbirths, miscarriages and terminations of pregnancy, smoking status, previous premature delivery). The following combinations of parameters were investigated in particular: rates of prematurity according to the number of previous stillbirths, miscarriages, and terminations; rates of prematurity according to the number of previous live births and maternal age, height and weight. We also included daily cigarette consumption and previous premature deliveries in our analyses. The rate of prematurity (premature deliveries (32-36 weeks) was 5.9%, and the rate of very early premature deliveries (prematurity (prematurity of 27.5% in women with the following combination of parameters: > or =1 stillbirth, > or =2 terminations of pregnancy and > or =2 miscarriages. A rather high risk of premature delivery (>11%) was also found for elderly (> or =40 years) grand multiparous women as well as small (premature deliveries (>10%). The risk table that we present here may assist in predicting premature delivery. Georg Thieme Verlag KG Stuttgart.New York.

  12. Premature aging in telomerase-deficient zebrafish

    Directory of Open Access Journals (Sweden)

    Monique Anchelin

    2013-09-01

    The study of telomere biology is crucial to the understanding of aging and cancer. In the pursuit of greater knowledge in the field of human telomere biology, the mouse has been used extensively as a model. However, there are fundamental differences between mouse and human cells. Therefore, additional models are required. In light of this, we have characterized telomerase-deficient zebrafish (Danio rerio as the second vertebrate model for human telomerase-driven diseases. We found that telomerase-deficient zebrafish show p53-dependent premature aging and reduced lifespan in the first generation, as occurs in humans but not in mice, probably reflecting the similar telomere length in fish and humans. Among these aging symptoms, spinal curvature, liver and retina degeneration, and infertility were the most remarkable. Although the second-generation embryos died in early developmental stages, restoration of telomerase activity rescued telomere length and survival, indicating that telomerase dosage is crucial. Importantly, this model also reproduces the disease anticipation observed in humans with dyskeratosis congenita (DC. Thus, telomerase haploinsufficiency leads to anticipation phenomenon in longevity, which is related to telomere shortening and, specifically, with the proportion of short telomeres. Furthermore, p53 was induced by telomere attrition, leading to growth arrest and apoptosis. Importantly, genetic inhibition of p53 rescued the adverse effects of telomere loss, indicating that the molecular mechanisms induced by telomere shortening are conserved from fish to mammals. The partial rescue of telomere length and longevity by restoration of telomerase activity, together with the feasibility of the zebrafish for high-throughput chemical screening, both point to the usefulness of this model for the discovery of new drugs able to reactivate telomerase in individuals with DC.

  13. The human endolymphatic sac expresses natriuretic peptides

    DEFF Research Database (Denmark)

    Møller, Martin Nue; Kirkeby, Svend; Vikeså, Jonas

    2017-01-01

    : Several natriuretic peptides were found expressed significantly in the ES, including uroguanylin and brain natriuretic peptide, but also peptides regulating vascular tone, including adrenomedullin 2. In addition, both neurophysin and oxytocin (OXT) were found significantly expressed. All peptides were...... verified by immunohistochemistry. CONCLUSION: The present data support the hypothesis that the human ES may have an endocrine/paracrine capacity through expression of several peptides with potent natriuretic activity. Furthermore, the ES may influence the hypothalamo-pituitary-adrenal axis and may regulate...... vasopressin receptors and aquaporin-2 channels in the inner ear via OXT expression. We hypothesize that the ES is likely to regulate inner ear endolymphatic homeostasis, possibly through secretion of several peptides, but it may also influence systemic and/or intracranial blood pressure through direct...

  14. The use of premature chromosome condensation to study in interphase cells the influence of environmental factors on human genetic material

    Directory of Open Access Journals (Sweden)

    Vasiliki I. Hatzi

    2006-01-01

    Full Text Available Nowadays, there is a constantly increasing concern regarding the mutagenic and carcinogenic potential of a variety of harmful environmental factors to which humans are exposed in their natural and anthropogenic environment. These factors exert their hazardous potential in humans' personal (diet, smoking, pharmaceuticals, cosmetics and occupational environment that constitute part of the anthropogenic environment. It is well known that genetic damage due to these factors has dramatic implications for human health. Since most of the environmental genotoxic factors induce arrest or delay in cell cycle progression, the conventional analysis of chromosomes at metaphase may underestimate their genotoxic potential. Premature Chromosome Condensation (PCC induced either by means of cell fusion or specific chemicals, enables the microscopic visualization of interphase chromosomes whose morphology depends on the cell cycle stage, as well as the analysis of structural and numerical aberrations at the G1 and G2 phases of the cell cycle. The PCC has been successfully used in problems involving cell cycle analysis, diagnosis and prognosis of human leukaemia, assessment of interphase chromosome malformations resulting from exposure to radiation or chemicals, as well as elucidation of the mechanisms underlying the conversion of DNA damage into chromosomal damage. In this report, particular emphasis is given to the advantages of the PCC methodology used as an alternative to conventional metaphase analysis in answering questions in the fields of radiobiology, biological dosimetry, toxicogenetics, clinical cytogenetics and experimental therapeutics.

  15. Risk Factors for premature birth in a hospital 1

    OpenAIRE

    Ahumada-Barrios, Margarita E.; Alvarado, German F.

    2016-01-01

    Abstract Objective: to determine the risk factors for premature birth. Methods: retrospective case-control study of 600 pregnant women assisted in a hospital, with 298 pregnant women in the case group (who gave birth prematurely

  16. Faktor Ibu yang Mempengaruhi Persalinan Prematur di RSUD Arifin Achmad Pekanbar

    Directory of Open Access Journals (Sweden)

    Liva Maita

    2012-11-01

    Full Text Available Persalinan prematur atau Partus Prematurus adalah persalinan yang terjadi pada usia kehamilan kurang dari 37 minggu dihitung dari hari pertama haid terakhir. Data di RSUD Arifin Achmad Pekanbaru didapatkan data pada tahun 2010 didapatkan data jumlah persalinan sebanyak 2400 kasus, dengan persalinan prematur 190 kasus (7,91%, tahun 2011 jumlah persalinan sebanyak 2287 kasus dengan persalinan prematur 279 kasus (12% dan pada periode Januari-April 2012 jumlah persalinan prematur 780 kasus (11,5%. Tujuan penelitian adalah diketahuinya hubungan dari komplikasi kehamilan, riwayat persalinan prematur, anemia, umur dan paritas dengan persalinan prematur. Jenis penelitian yang digunakan adalah studi kasus kontrol. Populasi dalam penelitian ini adalah seluruh ibu bersalin di RSUD Arifin achmad Pekanbaru. Besarnya sampel terdiri dari 245 kasus dan 245 kontrol. Analisis data dilakukan secara univariat, bivariat dan multivariat dengan metode Regresi Logistic Ganda. Hasil penelitian adalah komplikasi kehamilan (95% CI: 4,09-9,21, umur (CI 95%: 1,58-3,69, dan paritas (95% CI: 1,05-2,36 berhubungan dengan persalinan prematur. Kesimpulan yaitu variabel dominan yang berhubungan dengan kejadian persalinan prematur adalah komplikasi kehamilan dan tidak ada variabel counfounding. Saran kepada ibu hamil yang mengalami komplikasi kehamilan untuk memeriksakan kehamilan secara teratur minimal 4 kali selama kehamilan; pada ibu paritas tinggi disarankan menggunakan kontrasepsi mantap; dan Kepada tenaga kesehatan dapat mengelompokkan status pasien yang berisiko untuk mempermudah pemberian KIE

  17. Acute Associations Between Outdoor Temperature and Premature Rupture of Membranes.

    Science.gov (United States)

    Ha, Sandie; Liu, Danping; Zhu, Yeyi; Sherman, Seth; Mendola, Pauline

    2018-03-01

    Extreme ambient temperatures have been linked to preterm birth. Preterm premature rupture of membranes is a common precursor to preterm birth but is rarely studied in relation to temperature. We linked 15,381 singleton pregnancies with premature rupture of membranes from a nationwide US obstetrics cohort (2002-2008) to local temperature. Case-crossover analyses compared daily temperature during the week preceding delivery and the day of delivery to 2 control periods, before and after the case period. Conditional logistic regression models calculated the odds ratio (OR) and 95% confidence intervals (CIs) of preterm and term premature rupture of membranes for a 1°C increase in temperature during the warm (May-September) and cold (October-April) season separately after adjusting for humidity, barometric pressure, ozone, and particulate matter. During the warm season, 1°C increase during the week before delivery was associated with a 5% (95% CI, 3%, 6%) increased preterm premature rupture of membranes risk, and a 4% (95% CI, 3%, 5%) increased term premature rupture of membranes risk. During the cold season, 1°C increase was associated with a 2% decreased risk for both preterm (95% CI, 1%, 3%) and term premature rupture of membranes (95% CI, 1%, 3%). The day-specific associations for the week before delivery were similar, but somewhat stronger for days closer to delivery. Relatively small ambient temperature changes were associated with the risk of both preterm and term premature of membranes. Given the adverse consequences of premature rupture of membranes and concerns over global climate change, these findings merit further investigation. See video abstract at, http://links.lww.com/EDE/B312.

  18. Premature aging

    International Nuclear Information System (INIS)

    Sassaki, Hideo

    1992-01-01

    The hypothesis that radiation may accelerate aging phenomenon has been studied extensively, using the population of A-bomb survivors. In this paper, non-specific radiation-induced premature aging is discussed with a review of the literature. Cardiac lipofuscin, papillary fibrosis, aortic extensibility, hexamine/collagen ratio in the skin and aorta, testicular changes, giant hepatic cell nucleus, and neurofibril changes have so far been studied pathologically in the context of A-bomb radiation. Only testicular sclerosis has been found to correlate with distance from the hypocenter. Suggestive correlation was found to exist between the hexamine/collagen ratio in the skin and aorta and A-bomb radiation. Grip strength and hearing ability were decreased in the group of 100 rad and the group of 50-99 rad, respectively. The other physiological data did not definitely correlate with A-bomb radiation. Laboratory data, including erythrocyte sedimentation rate, α and β globulin levels, phytohemagglutinin reaction, T cell counts, erythrocyte glycophorin-A, the incidence of cerebral stroke, ischemic heart disease, and cataract were age-dependent and correlated with A-bomb radiation. These findings indicated that the occurrence of arteriosclerosis-related diseases, changes in immunological competence, and some pathological and physiological findings altered with advancing age, suggesting the correlation with A-bomb radiation. In general, it cannot be concluded that there is a positive correlation between A-bomb radiation and the premature aging. (N.K.) 51 refs

  19. Characterization of gene expression regulated by human OTK18 ...

    Indian Academy of Sciences (India)

    ing regulated by interactions with the Tat protein (Carlson et al. 2004a). In contrast, OTK18 is ubiquitously expressed in all normal human tissues, and OTK18 expression in HIV-1 ..... and Social Sciences and the UNK Biology Department.

  20. Down-regulation of Wild-type p53-induced Phosphatase 1 (Wip1) Plays a Critical Role in Regulating Several p53-dependent Functions in Premature Senescent Tumor Cells*

    Science.gov (United States)

    Crescenzi, Elvira; Raia, Zelinda; Pacifico, Francesco; Mellone, Stefano; Moscato, Fortunato; Palumbo, Giuseppe; Leonardi, Antonio

    2013-01-01

    Premature or drug-induced senescence is a major cellular response to chemotherapy in solid tumors. The senescent phenotype develops slowly and is associated with chronic DNA damage response. We found that expression of wild-type p53-induced phosphatase 1 (Wip1) is markedly down-regulated during persistent DNA damage and after drug release during the acquisition of the senescent phenotype in carcinoma cells. We demonstrate that down-regulation of Wip1 is required for maintenance of permanent G2 arrest. In fact, we show that forced expression of Wip1 in premature senescent tumor cells induces inappropriate re-initiation of mitosis, uncontrolled polyploid progression, and cell death by mitotic failure. Most of the effects of Wip1 may be attributed to its ability to dephosphorylate p53 at Ser15 and to inhibit DNA damage response. However, we also uncover a regulatory pathway whereby suppression of p53 Ser15 phosphorylation is associated with enhanced phosphorylation at Ser46, increased p53 protein levels, and induction of Noxa expression. On the whole, our data indicate that down-regulation of Wip1 expression during premature senescence plays a pivotal role in regulating several p53-dependent aspects of the senescent phenotype. PMID:23612976

  1. The expression of Egfl7 in human normal tissues and epithelial tumors.

    Science.gov (United States)

    Fan, Chun; Yang, Lian-Yue; Wu, Fan; Tao, Yi-Ming; Liu, Lin-Sen; Zhang, Jin-Fan; He, Ya-Ning; Tang, Li-Li; Chen, Guo-Dong; Guo, Lei

    2013-04-23

    To investigate the expression of Egfl7 in normal adult human tissues and human epithelial tumors.
 RT-PCR and Western blot were employed to detect Egfl7 expression in normal adult human tissues and 10 human epithelial tumors including hepatocellular carcinoma (HCC), lung cancer, breast cancer, prostate cancer, colorectal cancer, gastric cancer, esophageal cancer, malignant glioma, ovarian cancer and renal cancer. Immunohistochemistry and cytoimmunofluorescence were subsequently used to determine the localization of Egfl7 in human epithelial tumor tissues and cell lines. ELISA was also carried out to examine the serum Egfl7 levels in cancer patients. In addition, correlations between Egfl7 expression and clinicopathological features as well as prognosis of HCC and breast cancer were also analyzed on the basis of immunohistochemistry results.
 Egfl7 was differentially expressed in 19 adult human normal tissues and was overexpressed in all 10 human epithelial tumor tissues. The serum Egfl7 level was also significantly elevated in cancer patients. The increased Egfl7 expression in HCC correlated with vein invasion, absence of capsule formation, multiple tumor nodes and poor prognosis. Similarly, upregulation of Egfl7 in breast cancer correlated strongly with TNM stage, lymphatic metastasis, estrogen receptor positivity, Her2 positivity and poor prognosis. 
 Egfl7 is significantly upregulated in human epithelial tumor tissues, suggesting Egfl7 to be a potential biomarker for human epithelial tumors, especially HCC and breast cancer.

  2. Association of Maternal Preeclampsia With Infant Risk of Premature Birth and Retinopathy of Prematurity.

    Science.gov (United States)

    Shulman, Julia P; Weng, Cindy; Wilkes, Jacob; Greene, Tom; Hartnett, M Elizabeth

    2017-09-01

    Studies report conflicting associations between preeclampsia and retinopathy of prematurity (ROP). This study provides explanations for the discrepancies to clarify the relationship between preeclampsia and ROP. To evaluate the association of maternal preeclampsia and risk of ROP among infants in an unrestricted birth cohort and a restricted subcohort of preterm, very low birth weight (P-VLBW) infants. A retrospective review of 290 992 live births within the Intermountain Healthcare System in Utah from January 1, 2001, through December 31, 2010, was performed. Generalized estimating equations for logistic regressions with covariate adjustment were applied to relate ROP to preeclampsia among the full cohort and in a subcohort of P-VLBW infants born at younger than 31 weeks' gestation and weighing less than 1500 g. The occurrence of ROP was related to maternal preeclampsia in the full cohort and in a subcohort of P-VLBW infants. In the full cohort, 51% of the infants were male and the mean (SD) gestational age was 38.38 (1.87) weeks. In the P-VLBW cohort, 55% were male and the mean (SD) gestational age was 26.87 (2.40) weeks. In the full cohort, preeclampsia was associated with an increased risk of all ROP (adjusted odds ratio [aOR], 2.46; 95% CI, 2.17-2.79; P prematurity, because prematurity is an outcome of preeclampsia.

  3. Effects of pre-pregnancy obesity, race/ethnicity and prematurity.

    Science.gov (United States)

    de Jongh, B E; Paul, D A; Hoffman, M; Locke, R

    2014-04-01

    To investigate the association between maternal pre-pregnancy obesity, race/ethnicity and prematurity. Retrospective cohort study of maternal deliveries at a single regional center from 2009 to 2010 time period (n = 11,711). Generalized linear models were used for the analysis to estimate an adjusted odds ratio with 95% confidence interval of the association between maternal pre-pregnancy obesity, race/ethnicity and prematurity. Analysis controlled for diabetes, chronic hypertension, previous preterm birth, smoking and insurance status. The demographics of the study population were as follows, race/ethnicity had predominance in the White/Non-Hispanic population with 60.1%, followed by the Black/Non-Hispanic population 24.2%, the Hispanic population with 10.3% and the Asian population with 5.4%. Maternal pre-pregnancy weight showed that the population with a normal body mass index (BMI) was 49.4%, followed by the population being overweight with 26.2%, and last, the population which was obese with 24.4%. Maternal obesity increased the odds of prematurity in the White/Non-Hispanic, Hispanic and Asian population (aOR 1.40, CI 1.12-1.75; aOR 2.20, CI 1.23-3.95; aOR 3.07, CI 1.16-8.13, respectively). Although the Black/Non-Hispanic population prematurity rate remains higher than the other race/ethnicity populations, the Black/Non-Hispanic population did not have an increased odds of prematurity in obese mothers (OR 0.87; CI 0.68-1.19). Unlike White/Non-Hispanic, Asian and Hispanic mothers, normal pre-pregnancy BMI in Black/Non-Hispanic mothers was not associated with lower odds for prematurity. The odds for mothers of the White/Non-Hispanic, Hispanic and Asian populations, for delivering a premature infant, were significantly increased when obese. Analysis controlled for chronic hypertension, diabetes, insurance status, prior preterm birth and smoking. Obesity is a risk factor for prematurity in the White/Non-Hispanic, Asian and Hispanic population, but not for the

  4. Balance in children born prematurely currently aged 6–7

    Directory of Open Access Journals (Sweden)

    Dziuba Ewa

    2017-12-01

    Full Text Available Study aim: Premature birth is one of the major problems of obstetrics, leading to numerous complications that are associated with prematurity, for instance balance disorders. The aim of the study was to assess the impact of premature birth on the ability to maintain balance in children commencing their school education. Material and methods: The study included children aged 6-7 years. The study group consisted of 59 children (31 girls and 28 boys, mean age 6.38 ± SD 0.73 born prematurely between 24 and 35 weeks of gestation. The control group consisted of 61 children (28 girls and 33 boys, mean age 6.42 ± 0.58 born at term. The research utilized standardized test tools - one-leg open-eyed and closed-eyed standing test, one-leg jumping test - and an original questionnaire survey. Results: The children born at term achieved better results in the majority of tests. The comparison of girls and boys born pre­maturely and at term showed no statistically significant difference between them in terms of dynamic balance, static balance or total balance control. The comparison of the tests performed on the right and left lower limb in prematurely born children showed no statistically significant differences. Conclusion: Premature birth affects the ability to maintain body balance. The results of the study indicate the need to develop coordination skills that shape body balance in prematurely born children.

  5. EVALUATING THE EFFECTIVENESS OF ELKAR (L-CARNITINE IN PREMATURE INFANTS

    Directory of Open Access Journals (Sweden)

    Svetlana V. Garina

    2016-06-01

    Full Text Available Introduction. Recently in Russia there is a tendency to increase the proportion of premature infants, prolonged postnatal adaptation which may be associated with carnitine deficiency Early diagnosis and correction of carnitine deficiency in premature infants is possible to reserve the prevention of pathological conditions of the prenatal period in these patients. Materials and Methods. 98 newborn infants have been examined with the help of clinical laboratory methods. Results. It has been stated that the overwhelming majority of newborn infants irrespective of their gestational age and body mass at the moment of birth had reference ranges of crude carnitine and higher degree of floating carnitine in their peripheral blood within the first days of their lives. These changes are particularly characteristic for small pre-mature infants. Statistically significant differences between the levels of crude carnitine and floating carnitine depended on the gender of newborn infants have been revealed. Directly correlated dependence of the level of crude carnitine on the body mass at the moment of birth of small premature infants has been stated. Discussion and Conclusions. It has been proved that implementing L-carnitine into the development care plan for premature infants facilitates quick body weight gain, significantly cuts down the period of tube feeding, lowers frequency of anemia development of premature infants and duration of neonatal jaundice. The ability of Elkar to correct functional diseases of cardio vascular system of premature infants has been shown.

  6. Human cancer cells express Slug-based epithelial-mesenchymal transition gene expression signature obtained in vivo

    International Nuclear Information System (INIS)

    Anastassiou, Dimitris; Rumjantseva, Viktoria; Cheng, Weiyi; Huang, Jianzhong; Canoll, Peter D; Yamashiro, Darrell J; Kandel, Jessica J

    2011-01-01

    The biological mechanisms underlying cancer cell motility and invasiveness remain unclear, although it has been hypothesized that they involve some type of epithelial-mesenchymal transition (EMT). We used xenograft models of human cancer cells in immunocompromised mice, profiling the harvested tumors separately with species-specific probes and computationally analyzing the results. Here we show that human cancer cells express in vivo a precise multi-cancer invasion-associated gene expression signature that prominently includes many EMT markers, among them the transcription factor Slug, fibronectin, and α-SMA. We found that human, but not mouse, cells express the signature and Slug is the only upregulated EMT-inducing transcription factor. The signature is also present in samples from many publicly available cancer gene expression datasets, suggesting that it is produced by the cancer cells themselves in multiple cancer types, including nonepithelial cancers such as neuroblastoma. Furthermore, we found that the presence of the signature in human xenografted cells was associated with a downregulation of adipocyte markers in the mouse tissue adjacent to the invasive tumor, suggesting that the signature is triggered by contextual microenvironmental interactions when the cancer cells encounter adipocytes, as previously reported. The known, precise and consistent gene composition of this cancer mesenchymal transition signature, particularly when combined with simultaneous analysis of the adjacent microenvironment, provides unique opportunities for shedding light on the underlying mechanisms of cancer invasiveness as well as identifying potential diagnostic markers and targets for metastasis-inhibiting therapeutics

  7. Human T-lymphotropic virus type I tax regulates the expression of the human lymphotoxin gene.

    Science.gov (United States)

    Tschachler, E; Böhnlein, E; Felzmann, S; Reitz, M S

    1993-01-01

    Human T-lymphotropic virus type-I (HTLV-I)-infected T-cell lines constitutively produce high levels of lymphotoxin (LT). To analyze the mechanisms that lead to the expression of LT in HTLV-I-infected cell lines, we studied regulatory regions of the human LT promoter involved in the activation of the human LT gene. As determined by deletional analysis, sequences between +137 and -116 (relative to the transcription initiation site) are sufficient to direct expression of a reporter gene in the HTLV-I-infected cell line MT-2. Site-directed mutation of a of the single kappa B-like motif present in the LT promoter region (positions -99 to -89) completely abrogated LT promoter activity in MT-2 cells, suggesting that this site plays a critical role in the activation of the human LT gene. Transfection of LT constructs into HTLV-I-uninfected and -unstimulated Jurkat and U937 cell lines showed little to no activity of the LT promoter. Cotransfection of the same constructs with a tax expression plasmid into Jurkat cells led to detectable promoter activity, which could be significantly increased by stimulation of the cells with phorbol myristate acetate (PMA). Similarly, cotransfection of the LT promoter constructs and the tax expression plasmid into U937 cells led to significant promoter activity upon stimulation with PMA. These data suggest that HTLV-I tax is involved in the upregulation of LT gene expression in HTLV-I-infected cells.

  8. Premature hair greying may predict reduced bone mineral density in Graves' disease.

    LENUS (Irish Health Repository)

    Leary, A C

    2012-02-03

    BACKGROUND: Premature hair greying has been associated with low bone mineral density (BMD), and it may be more frequent in Graves\\' disease. AIMS: To determine whether premature greying is associated with reduced BMD in women with Graves\\' disease and in control women, and to examine whether premature greying is more common in Graves\\' disease. METHODS: Premature greying (> 50% grey by 40 years) and BMD were determined in 44 women with a history of Graves\\' disease and 133 female controls referred for routine BMD measurement. Exclusion criteria included diseases or drugs known to affect BMD. RESULTS: Mean Z and T scores at the lumbar spine were significantly lower (P < 0.04) in subjects with premature greying than in those not prematurely grey among women with Graves\\' disease, but not among control women. Multiple regression confirmed this difference between Graves\\' and control women (P = 0.041). There were no differences at other measurement sites. Of Graves\\' patients, 36% were prematurely grey compared with 25% of control women (P = 0.14). CONCLUSION: Premature greying may be a weak marker for reduced BMD in women with a history of Graves\\' disease, but it is not a marker in normal women.

  9. Bartter syndrome: presentation in an extremely premature neonate.

    Science.gov (United States)

    Flores, F X; Ojeda, F J; Calhoun, D A

    2013-08-01

    Reports of Bartter syndrome in premature neonates are rare. We describe the presentation and clinical course of a neonate born at 25.6 weeks estimated gestational age with polyuria, hyponatremia, hypokalemia and hypercalciuria ,who was diagnosed with neonatal Bartter syndrome. The evaluation, diagnosis and management of neonatal Bartter syndrome in this premature neonate are discussed.

  10. Investigation of G72 (DAOA expression in the human brain

    Directory of Open Access Journals (Sweden)

    Hirsch Steven

    2008-12-01

    Full Text Available Abstract Background Polymorphisms at the G72/G30 locus on chromosome 13q have been associated with schizophrenia or bipolar disorder in more than ten independent studies. Even though the genetic findings are very robust, the physiological role of the predicted G72 protein has thus far not been resolved. Initial reports suggested G72 as an activator of D-amino acid oxidase (DAO, supporting the glutamate dysfunction hypothesis of schizophrenia. However, these findings have subsequently not been reproduced and reports of endogenous human G72 mRNA and protein expression are extremely limited. In order to better understand the function of this putative schizophrenia susceptibility gene, we attempted to demonstrate G72 mRNA and protein expression in relevant human brain regions. Methods The expression of G72 mRNA was studied by northern blotting and semi-quantitative SYBR-Green and Taqman RT-PCR. Protein expression in human tissue lysates was investigated by western blotting using two custom-made specific anti-G72 peptide antibodies. An in-depth in silico analysis of the G72/G30 locus was performed in order to try and identify motifs or regulatory elements that provide insight to G72 mRNA expression and transcript stability. Results Despite using highly sensitive techniques, we failed to identify significant levels of G72 mRNA in a variety of human tissues (e.g. adult brain, amygdala, caudate nucleus, fetal brain, spinal cord and testis human cell lines or schizophrenia/control post mortem BA10 samples. Furthermore, using western blotting in combination with sensitive detection methods, we were also unable to detect G72 protein in a number of human brain regions (including cerebellum and amygdala, spinal cord or testis. A detailed in silico analysis provides several lines of evidence that support the apparent low or absent expression of G72. Conclusion Our results suggest that native G72 protein is not normally present in the tissues that we analysed

  11. Impaired Sleep, Circadian Rhythms and Neurogenesis in Diet-Induced Premature Aging

    Directory of Open Access Journals (Sweden)

    Alexander J. Stankiewicz

    2017-10-01

    Full Text Available Chronic high caloric intake (HCI is a risk factor for multiple major human disorders, from diabetes to neurodegeneration. Mounting evidence suggests a significant contribution of circadian misalignment and sleep alterations to this phenomenon. An inverse temporal relationship between sleep, activity, food intake, and clock mechanisms in nocturnal and diurnal animals suggests that a search for effective therapeutic approaches can benefit from the use of diurnal animal models. Here, we show that, similar to normal aging, HCI leads to the reduction in daily amplitude of expression for core clock genes, a decline in sleep duration, an increase in scoliosis, and anxiety-like behavior. A remarkable decline in adult neurogenesis in 1-year old HCI animals, amounting to only 21% of that in age-matched Control, exceeds age-dependent decline observed in normal 3-year old zebrafish. This is associated with misalignment or reduced amplitude of daily patterns for principal cell cycle regulators, cyclins A and B, and p20, in brain tissue. Together, these data establish HCI in zebrafish as a model for metabolically induced premature aging of sleep, circadian functions, and adult neurogenesis, allowing for a high throughput approach to mechanistic studies and drug trials in a diurnal vertebrate.

  12. Gene expression and functional annotation of the human and mouse choroid plexus epithelium.

    Directory of Open Access Journals (Sweden)

    Sarah F Janssen

    Full Text Available BACKGROUND: The choroid plexus epithelium (CPE is a lobed neuro-epithelial structure that forms the outer blood-brain barrier. The CPE protrudes into the brain ventricles and produces the cerebrospinal fluid (CSF, which is crucial for brain homeostasis. Malfunction of the CPE is possibly implicated in disorders like Alzheimer disease, hydrocephalus or glaucoma. To study human genetic diseases and potential new therapies, mouse models are widely used. This requires a detailed knowledge of similarities and differences in gene expression and functional annotation between the species. The aim of this study is to analyze and compare gene expression and functional annotation of healthy human and mouse CPE. METHODS: We performed 44k Agilent microarray hybridizations with RNA derived from laser dissected healthy human and mouse CPE cells. We functionally annotated and compared the gene expression data of human and mouse CPE using the knowledge database Ingenuity. We searched for common and species specific gene expression patterns and function between human and mouse CPE. We also made a comparison with previously published CPE human and mouse gene expression data. RESULTS: Overall, the human and mouse CPE transcriptomes are very similar. Their major functionalities included epithelial junctions, transport, energy production, neuro-endocrine signaling, as well as immunological, neurological and hematological functions and disorders. The mouse CPE presented two additional functions not found in the human CPE: carbohydrate metabolism and a more extensive list of (neural developmental functions. We found three genes specifically expressed in the mouse CPE compared to human CPE, being ACE, PON1 and TRIM3 and no human specifically expressed CPE genes compared to mouse CPE. CONCLUSION: Human and mouse CPE transcriptomes are very similar, and display many common functionalities. Nonetheless, we also identified a few genes and pathways which suggest that the CPE

  13. Efficacy of Intravitreal Bevacizumab for Stage 3+ Retinopathy of Prematurity

    Science.gov (United States)

    Mintz-Hittner, Helen A.; Kennedy, Kathleen A.; Chuang, Alice Z.

    2011-01-01

    BACKGROUND Retinopathy of prematurity is a leading cause of childhood blindness worldwide. Peripheral retinal ablation with conventional (confluent) laser therapy is destructive, causes complications, and does not prevent all vision loss, especially in cases of retinopathy of prematurity affecting zone I of the eye. Case series in which patients were treated with vascular endothelial growth factor inhibitors suggest that these agents may be useful in treating retinopathy of prematurity. METHODS We conducted a prospective, controlled, randomized, stratified, multicenter trial to assess intravitreal bevacizumab monotherapy for zone I or zone II posterior stage 3+ (i.e., stage 3 with plus disease) retinopathy of prematurity. Infants were randomly assigned to receive intravitreal bevacizumab (0.625 mg in 0.025 ml of solution) or conventional laser therapy, bilaterally. The primary ocular outcome was recurrence of retinopathy of prematurity in one or both eyes requiring retreatment before 54 weeks’ postmenstrual age. RESULTS We enrolled 150 infants (total sample of 300 eyes); 143 infants survived to 54 weeks’ postmenstrual age, and the 7 infants who died were not included in the primary-outcome analyses. Retinopathy of prematurity recurred in 4 infants in the bevacizumab group (6 of 140 eyes [4%]) and 19 infants in the laser-therapy group (32 of 146 eyes [22%], P = 0.002). A significant treatment effect was found for zone I retinopathy of prematurity (P = 0.003) but not for zone II disease (P = 0.27). CONCLUSIONS Intravitreal bevacizumab monotherapy, as compared with conventional laser therapy, in infants with stage 3+ retinopathy of prematurity showed a significant benefit for zone I but not zone II disease. Development of peripheral retinal vessels continued after treatment with intravitreal bevacizumab, but conventional laser therapy led to permanent destruction of the peripheral retina. This trial was too small to assess safety. PMID:21323540

  14. Human Milk Banking.

    Science.gov (United States)

    Haiden, Nadja; Ziegler, Ekhard E

    2016-01-01

    Human milk banks play an essential role by providing human milk to infants who would otherwise not be able to receive human milk. The largest group of recipients are premature infants who derive very substantial benefits from it. Human milk protects premature infants from necrotizing enterocolitis and from sepsis, two devastating medical conditions. Milk banks collect, screen, store, process, and distribute human milk. Donating women usually nurse their own infants and have a milk supply that exceeds their own infants' needs. Donor women are carefully selected and are screened for HIV-1, HIV-2, human T-cell leukemia virus 1 and 2, hepatitis B, hepatitis C, and syphilis. In the milk bank, handling, storing, processing, pooling, and bacterial screening follow standardized algorithms. Heat treatment of human milk diminishes anti-infective properties, cellular components, growth factors, and nutrients. However, the beneficial effects of donor milk remain significant and donor milk is still highly preferable in comparison to formula. © 2017 S. Karger AG, Basel.

  15. Cloning, sequencing, and expression of cDNA for human β-glucuronidase

    International Nuclear Information System (INIS)

    Oshima, A.; Kyle, J.W.; Miller, R.D.

    1987-01-01

    The authors report here the cDNA sequence for human placental β-glucuronidase (β-D-glucuronoside glucuronosohydrolase, EC 3.2.1.31) and demonstrate expression of the human enzyme in transfected COS cells. They also sequenced a partial cDNA clone from human fibroblasts that contained a 153-base-pair deletion within the coding sequence and found a second type of cDNA clone from placenta that contained the same deletion. Nuclease S1 mapping studies demonstrated two types of mRNAs in human placenta that corresponded to the two types of cDNA clones isolated. The NH 2 -terminal amino acid sequence determined for human spleen β-glucuronidase agreed with that inferred from the DNA sequence of the two placental clones, beginning at amino acid 23, suggesting a cleaved signal sequence of 22 amino acids. When transfected into COS cells, plasmids containing either placental clone expressed an immunoprecipitable protein that contained N-linked oligosaccharides as evidenced by sensitivity to endoglycosidase F. However, only transfection with the clone containing the 153-base-pair segment led to expression of human β-glucuronidase activity. These studies provide the sequence for the full-length cDNA for human β-glucuronidase, demonstrate the existence of two populations of mRNA for β-glucuronidase in human placenta, only one of which specifies a catalytically active enzyme, and illustrate the importance of expression studies in verifying that a cDNA is functionally full-length

  16. Zone 1 retinopathy of prematurity in a transitional economy: a cautionary note.

    Science.gov (United States)

    Carden, Susan M; Lan, Luu Ngoc; Huynh, Tess

    2006-06-01

    To describe three low risk infants in whom severe retinopathy of prematurity developed. A prospective, observational case series. setting: National Hospital of Pediatrics, Hanoi, Vietnam. study population: Premature infants in the neonatal ward. observation procedure: Eye examinations. Severe retinopathy of prematurity occurred in three infants. All had zone 1 disease and other unusually severe findings, such as neovascularization of the disk. These infants would not be at risk for the development of such severe retinopathy of prematurity in countries with a developed economy. Unusual characteristics of retinopathy of prematurity may be occurring in countries with transitional economies. Screening programs should be implemented and should take into consideration the possibility that retinopathy of prematurity may occur in infants who fall outside the screening guidelines that are used in the developed world.

  17. Structure and expression of human dihydropteridine reductase

    International Nuclear Information System (INIS)

    Lockyer, J.; Cook, R.G.; Milstien, S.; Kaufman, S.; Woo, S.L.C.; Ledley, F.D.

    1987-01-01

    Dihydropteridine reductase catalyzes the NADH-mediated reduction of quinonoid dihydrobiopterin and is an essential component of the pterindependent aromatic amino acid hydroxylating systems. A cDNA for human DHPR was isolated from a human liver cDNA library in the vector λgt11 using a monospecific antibody against sheep DHPR. The nucleic acid sequence and amino acid sequence of human DHPR were determined from a full-length clone. A 112 amino acid sequence of sheep DHPR was obtained by sequencing purified sheep DHPR. This sequence is highly homologous to the predicted amino acid sequence of the human protein. Gene transfer of the recombinant human DHPR into COS cells leads to expression of DHPR enzymatic activity. These results indicate that the cDNA clone identified by antibody screening is an authentic and full-length cDNA for human DHPR

  18. Premature Calcifications of Costal Cartilages: A New Perspective Premature Calcifications of Costal Cartilages: A New Perspective

    International Nuclear Information System (INIS)

    Rhomberg, W.; Schuster, A.

    2014-01-01

    Calcifications of the costal cartilages occur, as a rule, not until the age of 30 years. The knowledge of the clinical significance of early and extensive calcifications is still incomplete. Materials and Methods. A search was made to find patients below the age of 30 years who showed distinct calcifications of their lower costal cartilages by viewing 360 random samples of intravenous pyelograms and abdominal plain films. The histories, and clinical and laboratory findings of these patients were analyzed. Results. Nineteen patients fulfilled the criteria of premature calcifications of costal cartilages (CCCs). The patients had in common that they were frequently referred to a hospital and were treated by several medical disciplines. Nevertheless many complaints of the patients remained unsolved. Premature CCCs were often associated with rare endocrine disorders, inborn errors of metabolism, and abnormal hematologic findings. Among the metabolic disorders there were 2 proven porphyrias and 7 patients with a suspected porphyria but with inconclusive laboratory findings. Conclusion. Premature CCCs are unlikely to be a normal variant in skeletal radiology. The findings in this small group of patients call for more intensive studies, especially in regard to the putative role of a porphyria

  19. Gene expression and adaptive noncoding changes during human evolution.

    Science.gov (United States)

    Babbitt, Courtney C; Haygood, Ralph; Nielsen, William J; Wray, Gregory A

    2017-06-05

    Despite evidence for adaptive changes in both gene expression and non-protein-coding, putatively regulatory regions of the genome during human evolution, the relationship between gene expression and adaptive changes in cis-regulatory regions remains unclear. Here we present new measurements of gene expression in five tissues of humans and chimpanzees, and use them to assess this relationship. We then compare our results with previous studies of adaptive noncoding changes, analyzing correlations at the level of gene ontology groups, in order to gain statistical power to detect correlations. Consistent with previous studies, we find little correlation between gene expression and adaptive noncoding changes at the level of individual genes; however, we do find significant correlations at the level of biological function ontology groups. The types of function include processes regulated by specific transcription factors, responses to genetic or chemical perturbations, and differentiation of cell types within the immune system. Among functional categories co-enriched with both differential expression and noncoding adaptation, prominent themes include cancer, particularly epithelial cancers, and neural development and function.

  20. Antibiotics after preterm premature rupture of the membranes.

    Science.gov (United States)

    Singh, Katherine; Mercer, Brian

    2011-06-01

    Preterm premature rupture of the membranes remains a common cause of preterm deliveries and neonatal morbidities. The goal of this study is to review the evidence with regard to the antibiotic treatment after preterm premature rupture of the membranes, long-term outcomes related to antibiotic treatment, and possible complications with treatment. Future research goals are also discussed.

  1. Resveratrol Induced Premature Senescence Is Associated with DNA Damage Mediated SIRT1 and SIRT2 Down-Regulation.

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    Mehtap Kilic Eren

    agent doxorubicin also induced senescence in BJ fibroblasts associated with decreased SIRT1/2 levels. In conclusion our data reveal that resveratrol induced premature senescence is associated with SIRT1 and SIRT2 down regulation in human dermal fibroblasts. Here we suggest that the concomitant decline in SIRT1/2 expression in response to resveratrol treatment may be a cause for induction of senescence, which is most likely mediated by a regulatory mechanism activated by DNA damage response.

  2. System of the ophthalmologic help premature children with retinopathy of prematurity in the Central region of Russia

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    A. V. Tereshchenko

    2012-01-01

    Full Text Available Purpose: Functional results analysis of ophthalmologic help system for premature infants, which includes the full cycle of early revelation, treatment and regular medical check-up activities for patients with ROP in Central region of Russia.Methods: Fields for ROP screening were performed in premature infants medical care units by clinic specialists. Infants with re- vealed ROP were directed to Kaluga Branch of IRtC «Eye Microsurgery» for detailed diagnostic examination and subsequent treatment and monitoring.Results: In 2003-2011 454 fields in Kaluga, tula, Bryansk, and Orel regions were made. 8861 infants were examined. ROP was found in 1834 infants (20.7%. 823 different interventions for infants with active ROP were performed: 737 retinal lasercoagulations, 3-ports vitrectomy — 72, lensvitrectomy — 14. the total efficacy of the treatment was 92.9%.Conclusion: the ophthalmologic help system for premature infants in Central region of Russia combines all directions from de-tailed diagnostic to hich-technology treatment. It allows to reproduce one all over the Russian Federation territory.

  3. System of the ophthalmologic help premature children with retinopathy of prematurity in the Central region of Russia

    Directory of Open Access Journals (Sweden)

    A. V. Tereshchenko

    2014-07-01

    Full Text Available Purpose: Functional results analysis of ophthalmologic help system for premature infants, which includes the full cycle of early revelation, treatment and regular medical check-up activities for patients with ROP in Central region of Russia.Methods: Fields for ROP screening were performed in premature infants medical care units by clinic specialists. Infants with re- vealed ROP were directed to Kaluga Branch of IRtC «Eye Microsurgery» for detailed diagnostic examination and subsequent treatment and monitoring.Results: In 2003-2011 454 fields in Kaluga, tula, Bryansk, and Orel regions were made. 8861 infants were examined. ROP was found in 1834 infants (20.7%. 823 different interventions for infants with active ROP were performed: 737 retinal lasercoagulations, 3-ports vitrectomy — 72, lensvitrectomy — 14. the total efficacy of the treatment was 92.9%.Conclusion: the ophthalmologic help system for premature infants in Central region of Russia combines all directions from de-tailed diagnostic to hich-technology treatment. It allows to reproduce one all over the Russian Federation territory.

  4. Maternal Smoking during Pregnancy, Prematurity and Recurrent Wheezing in Early Childhood

    Science.gov (United States)

    Robison, Rachel G; Kumar, Rajesh; Arguelles, Lester M; Hong, Xiumei; Wang, Guoying; Apollon, Stephanie; Bonzagni, Anthony; Ortiz, Kathryn; Pearson, Colleen; Pongracic, Jacqueline A; Wang, Xiaobin

    2013-01-01

    Summary Background Prenatal maternal smoking and prematurity independently affect wheezing and asthma in childhood. Objective We sought to evaluate the interactive effects of maternal smoking and prematurity upon the development of early childhood wheezing. Methods We evaluated 1448 children with smoke exposure data from a prospective urban birth cohort in Boston. Maternal antenatal and postnatal exposure was determined from standardized questionnaires. Gestational age was assessed by the first day of the last menstrual period and early prenatal ultrasound (pretermprematurity and maternal antenatal smoking on recurrent wheeze, controlling for relevant covariates. Results In the cohort, 90 (6%) children had recurrent wheezing, 147 (10%) were exposed to in utero maternal smoke and 419 (29%) were premature. Prematurity (odds ratio [OR] 2.0; 95% CI, 1.3-3.1) was associated with an increased risk of recurrent wheezing, but in utero maternal smoking was not (OR 1.1, 95% CI 0.5-2.4). Jointly, maternal smoke exposure and prematurity caused an increased risk of recurrent wheezing (OR 3.8, 95% CI 1.8-8.0). There was an interaction between prematurity and maternal smoking upon episodes of wheezing (p=0.049). Conclusions We demonstrated an interaction between maternal smoking during pregnancy and prematurity on childhood wheezing in this urban, multiethnic birth cohort. PMID:22290763

  5. Large scale gene expression meta-analysis reveals tissue-specific, sex-biased gene expression in humans

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    Benjamin Mayne

    2016-10-01

    Full Text Available The severity and prevalence of many diseases are known to differ between the sexes. Organ specific sex-biased gene expression may underpin these and other sexually dimorphic traits. To further our understanding of sex differences in transcriptional regulation, we performed meta-analyses of sex biased gene expression in multiple human tissues. We analysed 22 publicly available human gene expression microarray data sets including over 2500 samples from 15 different tissues and 9 different organs. Briefly, by using an inverse-variance method we determined the effect size difference of gene expression between males and females. We found the greatest sex differences in gene expression in the brain, specifically in the anterior cingulate cortex, (1818 genes, followed by the heart (375 genes, kidney (224 genes, colon (218 genes and thyroid (163 genes. More interestingly, we found different parts of the brain with varying numbers and identity of sex-biased genes, indicating that specific cortical regions may influence sexually dimorphic traits. The majority of sex-biased genes in other tissues such as the bladder, liver, lungs and pancreas were on the sex chromosomes or involved in sex hormone production. On average in each tissue, 32% of autosomal genes that were expressed in a sex-biased fashion contained androgen or estrogen hormone response elements. Interestingly, across all tissues, we found approximately two-thirds of autosomal genes that were sex-biased were not under direct influence of sex hormones. To our knowledge this is the largest analysis of sex-biased gene expression in human tissues to date. We identified many sex-biased genes that were not under the direct influence of sex chromosome genes or sex hormones. These may provide targets for future development of sex-specific treatments for diseases.

  6. Room temperature housing results in premature cancellous bone loss in growing female mice: implications for the mouse as a preclinical model for age-related bone loss.

    Science.gov (United States)

    Iwaniec, U T; Philbrick, K A; Wong, C P; Gordon, J L; Kahler-Quesada, A M; Olson, D A; Branscum, A J; Sargent, J L; DeMambro, V E; Rosen, C J; Turner, R T

    2016-10-01

    Room temperature housing (22 °C) results in premature cancellous bone loss in female mice. The bone loss was prevented by housing mice at thermoneutral temperature (32 °C). Thermogenesis differs markedly between mice and humans and mild cold stress induced by standard room temperature housing may introduce an unrecognized confounding variable into preclinical studies. Female mice are often used as preclinical models for osteoporosis but, in contrast to humans, mice exhibit cancellous bone loss during growth. Mice are routinely housed at room temperature (18-23 °C), a strategy that exaggerates physiological differences in thermoregulation between mice (obligatory daily heterotherms) and humans (homeotherms). The purpose of this investigation was to assess whether housing female mice at thermoneutral (temperature range where the basal rate of energy production is at equilibrium with heat loss) alters bone growth, turnover and microarchitecture. Growing (4-week-old) female C57BL/6J and C3H/HeJ mice were housed at either 22 or 32 °C for up to 18 weeks. C57BL/6J mice housed at 22 °C experienced a 62 % cancellous bone loss from the distal femur metaphysis during the interval from 8 to 18 weeks of age and lesser bone loss from the distal femur epiphysis, whereas cancellous and cortical bone mass in 32 °C-housed mice were unchanged or increased. The impact of thermoneutral housing on cancellous bone was not limited to C57BL/6J mice as C3H/HeJ mice exhibited a similar skeletal response. The beneficial effects of thermoneutral housing on cancellous bone were associated with decreased Ucp1 gene expression in brown adipose tissue, increased bone marrow adiposity, higher rates of bone formation, higher expression levels of osteogenic genes and locally decreased bone resorption. Housing female mice at 22 °C resulted in premature cancellous bone loss. Failure to account for species differences in thermoregulation may seriously confound interpretation of studies

  7. Human eosinophils constitutively express a unique serine protease, PRSS33.

    Science.gov (United States)

    Toyama, Sumika; Okada, Naoko; Matsuda, Akio; Morita, Hideaki; Saito, Hirohisa; Fujisawa, Takao; Nakae, Susumu; Karasuyama, Hajime; Matsumoto, Kenji

    2017-07-01

    Eosinophils play important roles in asthma, especially airway remodeling, by producing various granule proteins, chemical mediators, cytokines, chemokines and proteases. However, protease production by eosinophils is not fully understood. In the present study, we investigated the production of eosinophil-specific proteases/proteinases by transcriptome analysis. Human eosinophils and other cells were purified from peripheral blood by density gradient sedimentation and negative/positive selections using immunomagnetic beads. Protease/proteinase expression in eosinophils and release into the supernatant were evaluated by microarray analysis, qPCR, ELISA, flow cytometry and immunofluorescence staining before and after stimulation with eosinophil-activating cytokines and secretagogues. mRNAs for extracellular matrix proteins in human normal fibroblasts were measured by qPCR after exposure to recombinant protease serine 33 (PRSS33) protein (rPRSS33), created with a baculovirus system. Human eosinophils expressed relatively high levels of mRNA for metalloproteinase 25 (MMP25), a disintegrin and metalloprotease 8 (ADAM8), ADAM10, ADAM19 and PRSS33. Expression of PRSS33 was the highest and eosinophil-specific. PRSS33 mRNA expression was not affected by eosinophil-activating cytokines. Immunofluorescence staining showed that PRSS33 was co-localized with an eosinophil granule protein. PRSS33 was not detected in the culture supernatant of eosinophils even after stimulation with secretagogues, but its cell surface expression was increased. rPRSS33 stimulation of human fibroblasts increased expression of collagen and fibronectin mRNAs, at least in part via protease-activated receptor-2 activation. Activated eosinophils may induce fibroblast extracellular matrix protein synthesis via cell surface expression of PRSS33, which would at least partly explain eosinophils' role(s) in airway remodeling. Copyright © 2017 Japanese Society of Allergology. Production and hosting by Elsevier

  8. Serbia within the European context: An analysis of premature mortality.

    Science.gov (United States)

    Santric Milicevic, Milena; Bjegovic, Vesna; Terzic, Zorica; Vukovic, Dejana; Kocev, Nikola; Marinkovic, Jelena; Vasic, Vladimir

    2009-08-05

    Based on the global predictions majority of deaths will be collectively caused by cancer, cardiovascular diseases, and traffic accidents over the coming 25 years. In planning future national health policy actions, inter - regional assessments play an important role. The purpose of the study was to analyze similarities and differences in premature mortality between Serbia, EURO A, EURO B, and EURO C regions in 2000. Mortality and premature mortality patterns were analysed according to cause of death, by gender and seven age intervals. The study results are presented in relative (%) and absolute terms (age-specific and age-standardized death rates per 100,000 population, and age-standardized rates of years of life lost - YLL per 1,000). Direct standardization of rates was undertaken using the standard population of Europe. The inter-regional comparison was based on a calculation of differences in YLL structures and with a ratio of age-standardized YLL rates per 1,000. A multivariate generalized linear model was used to explore mortality of Serbia and Europe sub-regions with ln age-specific death rates. The dissimilarity was achieved with a p financial and human resources incorporated in the prevention of disease and injury burden.

  9. Apnea of Prematurity (For Parents)

    Science.gov (United States)

    ... mature enough to allow nonstop breathing. This causes large bursts of breath followed by periods of shallow breathing or stopped breathing. Apnea of prematurity usually ends on its own after a few ...

  10. Sildenafil and retinopathy of prematurity risk in very low birth weight infants

    NARCIS (Netherlands)

    S. Samiee-Zafarghandy; J.N. van den Anker (John); M. Laughon (Matthew); R.H. Clark; P.B. Smith; C.P. Hornik

    2016-01-01

    textabstractObjective: To examine the effect of sildenafil therapy on development of severe retinopathy of prematurity (ROP) requiring surgical intervention in premature infants. Study Design: We identified premature infants who were discharged from Pediatrix Medical Group neonatal intensive care

  11. Stress-induced premature senescence of endothelial cells.

    Science.gov (United States)

    Chen, Jun; Patschan, Susann; Goligorsky, Michael S

    2008-01-01

    Stress-induced premature senescence (SIPS) is characterized by cell cycle arrest and curtailed Hayflick limit. Studies support a central role for Rb protein in controlling this process via signaling from the p53 and p16 pathways. Cellular senescence is considered an essential contributor to the aging process and has been shown to be an important tumor suppression mechanism. In addition, emerging evidence suggests that SIPS may be involved in the pathogenesis of chronic human diseases. Here, focusing on endothelial cells, we discuss recent advances in our understanding of SIPS and the pathways that trigger it, evaluate their correlation with the apoptotic response and examine their links to the development of chronic diseases, with the emphasis on vasculopathy. Emerging novel therapeutic interventions based on recent experimental findings are also reviewed.

  12. YY1 positively regulates human UBIAD1 expression

    International Nuclear Information System (INIS)

    Funahashi, Nobuaki; Hirota, Yoshihisa; Nakagawa, Kimie; Sawada, Natumi; Watanabe, Masato; Suhara, Yoshitomo; Okano, Toshio

    2015-01-01

    Vitamin K is involved in bone formation and blood coagulation. Natural vitamin K compounds are composed of the plant form phylloquinone (vitamin K 1 ) and a series of bacterial menaquionones (MK-n; vitamin K 2 ). Menadione (vitamin K 3 ) is an artificial vitamin K compound. MK-4 contains 4-isoprenyl as a side group in the 2-methyl-1,4-naphthoquinone common structure and has various bioactivities. UbiA prenyltransferase domain containing 1 (UBIAD1 or TERE1) is the menaquinone-4 biosynthetic enzyme. UBIAD1 transcript expression significantly decreases in patients with prostate carcinoma and overexpressing UBIAD1 inhibits proliferation of a tumour cell line. UBIAD1 mRNA expression is ubiquitous in mouse tissues, and higher UBIAD1 mRNA expression levels are detected in the brain, heart, kidneys and pancreas. Several functions of UBIAD1 have been reported; however, regulation of the human UBIAD1 gene has not been elucidated. Here we report cloning and characterisation of the human UBIAD1 promoter. A 5′ rapid amplification of cDNA ends analysis revealed that the main transcriptional start site was 306 nucleotides upstream of the translation initiation codon. Deletion and mutation analyses revealed the functional importance of the YY1 consensus motif. Electrophoretic gel mobility shift and chromatin immunoprecipitation assays demonstrated that YY1 binds the UBIAD1 promoter in vitro and in vivo. In addition, YY1 small interfering RNA decreased endogenous UBIAD1 mRNA expression and UBIAD1 conversion activity. These results suggest that YY1 up-regulates UBIAD1 expression and UBIAD1 conversion activity through the UBIAD1 promoter. - Highlights: • We cloned the human UBIAD1 promoter. • The functional importance of the YY1 motif was identified in the UBIAD1 promoter. • YY1 binds the UBIAD1 promoter in vitro and in vivo. • Knockdown of YY1 significantly decreased UBIAD1 expression. • YY1 up-regulates UBIAD1 conversion activity through the UBIAD1 promoter

  13. YY1 positively regulates human UBIAD1 expression

    Energy Technology Data Exchange (ETDEWEB)

    Funahashi, Nobuaki, E-mail: nfunahashi@ri.ncgm.go.jp [Department of Hygienic Sciences, Kobe Pharmaceutical University, Kobe (Japan); Department of Metabolic Disorder, Diabetes Research Center, Research Institute, National Center for Global Health and Medicine, Tokyo (Japan); Hirota, Yoshihisa [Department of Hygienic Sciences, Kobe Pharmaceutical University, Kobe (Japan); Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka (Japan); Nakagawa, Kimie; Sawada, Natumi; Watanabe, Masato [Department of Hygienic Sciences, Kobe Pharmaceutical University, Kobe (Japan); Suhara, Yoshitomo [Department of Bioscience and Engineering, Shibaura Institute of Technology, Saitama (Japan); Okano, Toshio [Department of Hygienic Sciences, Kobe Pharmaceutical University, Kobe (Japan)

    2015-05-01

    Vitamin K is involved in bone formation and blood coagulation. Natural vitamin K compounds are composed of the plant form phylloquinone (vitamin K{sub 1}) and a series of bacterial menaquionones (MK-n; vitamin K{sub 2}). Menadione (vitamin K{sub 3}) is an artificial vitamin K compound. MK-4 contains 4-isoprenyl as a side group in the 2-methyl-1,4-naphthoquinone common structure and has various bioactivities. UbiA prenyltransferase domain containing 1 (UBIAD1 or TERE1) is the menaquinone-4 biosynthetic enzyme. UBIAD1 transcript expression significantly decreases in patients with prostate carcinoma and overexpressing UBIAD1 inhibits proliferation of a tumour cell line. UBIAD1 mRNA expression is ubiquitous in mouse tissues, and higher UBIAD1 mRNA expression levels are detected in the brain, heart, kidneys and pancreas. Several functions of UBIAD1 have been reported; however, regulation of the human UBIAD1 gene has not been elucidated. Here we report cloning and characterisation of the human UBIAD1 promoter. A 5′ rapid amplification of cDNA ends analysis revealed that the main transcriptional start site was 306 nucleotides upstream of the translation initiation codon. Deletion and mutation analyses revealed the functional importance of the YY1 consensus motif. Electrophoretic gel mobility shift and chromatin immunoprecipitation assays demonstrated that YY1 binds the UBIAD1 promoter in vitro and in vivo. In addition, YY1 small interfering RNA decreased endogenous UBIAD1 mRNA expression and UBIAD1 conversion activity. These results suggest that YY1 up-regulates UBIAD1 expression and UBIAD1 conversion activity through the UBIAD1 promoter. - Highlights: • We cloned the human UBIAD1 promoter. • The functional importance of the YY1 motif was identified in the UBIAD1 promoter. • YY1 binds the UBIAD1 promoter in vitro and in vivo. • Knockdown of YY1 significantly decreased UBIAD1 expression. • YY1 up-regulates UBIAD1 conversion activity through the UBIAD1

  14. Expression of Sirtuins in the Retinal Neurons of Mice, Rats, and Humans

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    Hongdou Luo

    2017-11-01

    Full Text Available Sirtuins are a class of histone deacetylases (HDACs that have been shown to regulate a range of pathophysiological processes such as cellular aging, inflammation, metabolism, and cell proliferation. There are seven mammalian Sirtuins (SIRT1-7 that play important roles in stress response, aging, and neurodegenerative diseases. However, the location and function of Sirtuins in neurons are not well defined. This study assessed the retinal expression of Sirtuins in mice, rats, and humans and measured the expression of Sirtuins in aged and injured retinas. Expression of all 7 Sirtuins was confirmed by Western blot and Real-Time PCR analysis in all three species. SIRT1 is highly expressed in mouse, rat, and human retinas, whereas SIRT2-7 expression was relatively lower in human retinas. Immunofluorescence was also used to examine the expression and localization of Sirtuins in rat retinal neurons. Importantly, we demonstrate a marked reduction of SIRT1 expression in aged retinal neurons as well as retinas injured by acute ischemia-reperfusion. On the other hand, none of the other Sirtuins exhibit any significant age-related changes in expression except for SIRT5, which was significantly higher in the retinas of adults compared to both young and aged rats. Our work presents the first composite analysis of Sirtuins in the retinal neurons of mice, rats, and humans, and suggests that increasing the expression and activity of SIRT1 may be beneficial for the treatment of glaucoma and other age-related eye dysfunction.

  15. Expression of Recombinant Human Coagulation Factor VII by the Lizard Leishmania Expression System

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    Sina Mirzaahmadi

    2011-01-01

    Full Text Available The variety of recombinant protein expression systems have been developed as a resource of FVII gene expression. In the current study, the authors used a novel protein expression system based on the Iranian Lizard Leishmania, a trypanosomatid protozoan as a host for expression of FVII. Plasmid containing cDNA encoding full-length human FVII was introduced into Lizard Leishmania and positive transfectants were analyzed by SDS-PAGE and Western blot analysis. Furthermore, biological activity of purified protein was detected by PT assay. The recombinant strain harboring a construct was analyzed for expression of FVII at the mRNA and protein level. Purified rFVII was obtained and in order to confirm the purified compound was in fact rFVII. Western blot analysis was carried out. Clotting time in PT assay was reduced about 30 seconds with the purified rFVII. In Conclusion, this study has demonstrated, for the first time, that Leishmania cells can be used as an expression system for producing recombinant FVII.

  16. Analysis of aquaporin 9 expression in human epidermis and cultured keratinocytes

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    Yoshinori Sugiyama

    2014-01-01

    Full Text Available Aquaporin 9 (AQP9 is a member of the aquaglyceroporin family that transports glycerol, urea and other small solutes as well as water. Compared to the expression and function in epidermal keratinocytes of AQP3, another aquaglyceroporin, our knowledge of epidermal AQP9 remains elusive. In this study, we investigated the expression of AQP9 in the human epidermis and cultured keratinocytes. Immunofluorescence studies revealed that AQP9 expression is highly restricted to the stratum granulosum of the human epidermis, where occludin is also expressed at the tight junctions. Interestingly, the AQP3 staining decreased sharply below the cell layers in which AQP9 is expressed. In cultured normal human epidermal keratinocytes (NHEK, knock-down of AQP9 expression in the differentiated cells induced by RNA interference reduced glycerol uptake, which was not as pronounced as was the case with AQP3 knock-down cells. In contrast, similar reduction of urea uptake was detected in AQP9 and AQP3 knock-down cells. These findings suggested that AQP9 expression in NHEK facilitates at least the transport of glycerol and urea. Finally, we analyzed the effect of retinoic acid (RA, a potent stimulator of keratinocyte proliferation, on AQP3 and AQP9 mRNA expression in differentiated NHEK. Stimulation with RA at 1 μM for 24 h augmented AQP3 expression and down-regulated AQP9 expression. Collectively, these results indicate that AQP9 expression in epidermal keratinocytes is regulated in a different manner from that of AQP3.

  17. Transcriptional and epigenetic regulation of KIAA1199 gene expression in human breast cancer.

    Directory of Open Access Journals (Sweden)

    Cem Kuscu

    Full Text Available Emerging evidence has demonstrated that upregulated expression of KIAA1199 in human cancer bodes for poor survival. The regulatory mechanism controlling KIAA1199 expression in cancer remains to be characterized. In the present study, we have isolated and characterized the human KIAA1199 promoter in terms of regulation of KIAA1199 gene expression. A 3.3 kb fragment of human genomic DNA containing the 5'-flanking sequence of the KIAA1199 gene possesses both suppressive and activating elements. Employing a deletion mutagenesis approach, a 1.4 kb proximal region was defined as the basic KIAA1199 promoter containing a TATA-box close to the transcription start site. A combination of 5'-primer extension study with 5'RACE DNA sequencing analysis revealed one major transcription start site that is utilized in the human KIAA1199 gene. Bioinformatics analysis suggested that the 1.4 kb KIAA1199 promoter contains putative activating regulatory elements, including activator protein-1(AP-1, Twist-1, and NF-κB sites. Sequential deletion and site-direct mutagenesis analysis demonstrated that the AP-1 and distal NF-κB sites are required for KIAA1199 gene expression. Further analyses using an electrophoretic mobility-shift assay and chromatin immunoprecipitation confirmed the requirement of these cis- and trans-acting elements in controlling KIAA1199 gene expression. Finally, we found that upregulated KIAA1199 expression in human breast cancer specimens correlated with hypomethylation of the regulatory region. Involvement of DNA methylation in regulation of KIAA1199 expression was recapitulated in human breast cancer cell lines. Taken together, our study unraveled the regulatory mechanisms controlling KIAA1199 gene expression in human cancer.

  18. Acute effects of air pollution on spontaneous abortion, premature delivery, and stillbirth in Ahvaz, Iran: a time-series study.

    Science.gov (United States)

    Dastoorpoor, Maryam; Idani, Esmaeil; Goudarzi, Gholamreza; Khanjani, Narges

    2018-02-01

    Living in areas with high air pollution may have adverse effects on human health. There are few studies about the association between breathing polluted air and adverse pregnancy outcomes in the Middle East. The aim of this study was to determine the relationship between air pollution and spontaneous abortion, premature birth, and stillbirth in Ahvaz. A time-series study was conducted. Data about spontaneous abortion, premature deliveries, and stillbirth was collected from Ahvaz Imam Khomeini Hospital. Air pollution data including NO, CO, NO 2 , PM 10 , SO 2 , O 3 , and climate data were, respectively, collected from the Environmental Protection Agency and the Khuzestan Province Meteorology Office from March 2008 until March 2015. The relationship between air pollutants with the number of abortions, premature births, and stillbirths was found using a quasi-Poisson distributed lag model, adjusted by trend, seasonality, temperature, relative humidity, weekdays, and holidays. The average daily dust in Ahvaz on 7.2% days of the year was higher than 500 μg/m 3 (very dangerous). Findings from this study indicate a significant association between each 10-unit increase in SO 2 and spontaneous abortion in lag 0 and 9 days. There was a significant relation between each 10-unit increase in NO 2 and CO, and premature birth in lag 0. Also, we found a significant association between each 10-unit increase in CO and premature delivery in lag 1; PM 10 and premature delivery in lags 10, 11, and 12; and NO and premature delivery in lags 3, 4, 10, 11, 12, and 13 (p value polluted air during pregnancy may increase adverse pregnancy outcomes and stillbirth. Pregnant women should avoid polluted air.

  19. Premature Ejaculation and Utilization of Cognitive Techniques

    Directory of Open Access Journals (Sweden)

    Serkan AKKOYUNLU

    2013-04-01

    Discussion: Premature ejaculation is a male sexual dysfunction that causes distress and intimacy problems between couples. Stop start and squeeze techniques were accepted as the choice of treatment but their effectiveness is questioned recently. Also cognitive distortions and maladaptive beliefs may hamper therapy progress. Besides that, behavioral techniques utilizing cognitive techniques to lessen the degree of dysfunctional beliefs about sex and sexuality may help the couple to overcome premature ejaculation and enhance sexual satisfaction and intimacy. [JCBPR 2013; 2(1.000: 47-52

  20. Premature delivery

    Directory of Open Access Journals (Sweden)

    Bernardita Donoso Bernales

    2012-09-01

    Full Text Available Preterm delivery is the single most important cause of perinatal morbidity and mortality. In Chile, preterm births have increased in the past decade, although neonatal morbidity and mortality attributable to it shows a downward trend, thanks to improvements in neonatal care of premature babies, rather than the success of obstetric preventive and therapeutic strategies. This article describes clinical entities, disease processes and conditions that constitute predisposing factors of preterm birth, as well as an outline for the prevention and clinical management of women at risk of preterm birth.

  1. Analysis on screening results of 2 203 premature infants with retinopathy

    Directory of Open Access Journals (Sweden)

    Qian Wang

    2018-06-01

    Full Text Available AIM: To investigate the incidence and risk factors of retinopathy of prematurity(ROPin preterm infants. METHODS: The wide-field digital pediatric Retinal imaging system was used to screen 2 203 preterm infants with gestational age RESULTS: Totally 367 infants(621 eyeswere diagnosed as retinopathy among 2 203 premature infants and the incidence of ROP was 16.66%; 236 cases(399 eyesof ROP(26.61%were detected in 887 cases of premature infants in accord with screening standard of the Chinese Premature Retinopathy Screening Guidelines(2014, and 131 cases(222 eyesof ROP(9.95%was detected in 1 316 cases of premature infants outside the screening standard. In our research, the incidence of ROP was related with gestational age, birth weight, oxygen duration and mechanical ventilation. However, the relationship had not been found with artificial insemination, caesarean birth, gender, polyembryony, acute respiratory distress syndrome(ARDS, hypertensive disorders in pregnancy, gestational diabetes mellitus, intrauterine infection, intrauterine distress, premature rupture of membrane. The incidence of ROP was statistically significant between different gestational age groups, different birth weight groups and different oxygen groups(PCONCLUSION: The incidence of ROP is 16.66% in this study, and there is still a certain proportion outside the screening standard of the Chinese Premature Retinopathy Screening Guidelines(2014. Gestational age, birth weight, oxygen duration and mechanical ventilation are high risk factors for ROP.

  2. Chronological changes in microRNA expression in the developing human brain.

    Directory of Open Access Journals (Sweden)

    Michael P Moreau

    Full Text Available MicroRNAs (miRNAs are endogenously expressed noncoding RNA molecules that are believed to regulate multiple neurobiological processes. Expression studies have revealed distinct temporal expression patterns in the developing rodent and porcine brain, but comprehensive profiling in the developing human brain has not been previously reported.We performed microarray and TaqMan-based expression analysis of all annotated mature miRNAs (miRBase 10.0 as well as 373 novel, predicted miRNAs. Expression levels were measured in 48 post-mortem brain tissue samples, representing gestational ages 14-24 weeks, as well as early postnatal and adult time points.Expression levels of 312 miRNAs changed significantly between at least two of the broad age categories, defined as fetal, young, and adult.We have constructed a miRNA expression atlas of the developing human brain, and we propose a classification scheme to guide future studies of neurobiological function.

  3. Adverse respiratory outcome after premature rupture of membranes before viability.

    Science.gov (United States)

    Verspyck, Eric; Bisson, Violene; Roman, Horace; Marret, Stéphane

    2014-03-01

    To determine whether preterm premature rupture of membranes (PPROM) before 24 weeks is an independent risk factor for poor outcome in preterm neonates. A retrospective comparative cohort study was conducted, including viable premature infants born between 25 and 34-weeks gestation. Each preterm case with early PPROM was matched with two preterm controls of the same gestational age at birth, sex and birth date and who were born spontaneously with intact membranes. Logistic regression was performed to identify independent risk factors associated with composite respiratory and perinatal adverse outcomes for the overall population of preterm infants. Thirty-five PPROM cases were matched with 70 controls. Extreme prematurity (26-28 weeks) was an independent risk factor for composite perinatal adverse outcomes [odds ratio (OR) 43.9; p = 0.001]. Extreme prematurity (OR 42.9; p = 0.001), PPROM (OR 7.1; p = 0.01), male infant (OR 5.2; p = 0.02) and intrauterine growth restriction (IUGR, OR 4.8; p = 0.04) were factors for composite respiratory adverse outcomes. Preterm premature rupture of membranes before viability represents an independent risk factor for composite respiratory adverse outcomes in preterm neonates. Extreme prematurity may represent the main risk factor for both composite respiratory and perinatal adverse outcomes. ©2013 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  4. Early menarche, nulliparity and the risk for premature and early natural menopause.

    Science.gov (United States)

    Mishra, Gita D; Pandeya, Nirmala; Dobson, Annette J; Chung, Hsin-Fang; Anderson, Debra; Kuh, Diana; Sandin, Sven; Giles, Graham G; Bruinsma, Fiona; Hayashi, Kunihiko; Lee, Jung Su; Mizunuma, Hideki; Cade, Janet E; Burley, Victoria; Greenwood, Darren C; Goodman, Alissa; Simonsen, Mette Kildevæld; Adami, Hans-Olov; Demakakos, Panayotes; Weiderpass, Elisabete

    2017-03-01

    .80, 95% CI 1.53-2.12) and early menopause (1.31, 1.19-1.44). Nulliparity was associated with increased risk of premature menopause (2.26, 1.84-2.77) and early menopause (1.32, 1.09-1.59). Women having early menarche and nulliparity were at over 5-fold increased risk of premature menopause (5.64, 4.04-7.87) and 2-fold increased risk of early menopause (2.16, 1.48-3.15) compared with women who had menarche at ≥12 years and two or more children. Most of the studies (except the birth cohorts) relied on retrospectively reported age at menarche, which may have led to some degree of recall bias. Our findings support early monitoring of women with early menarche, especially those who have no children, for preventive health interventions aimed at mitigating the risk of adverse health outcomes associated with early menopause. InterLACE project is funded by the Australian National Health and Medical Research Council project grant (APP1027196). G.D.M. is supported by Australian Research Council Future Fellowship (FT120100812). There are no competing interests. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.

  5. The splicing mutant of the human tumor suppressor protein DFNA5 induces programmed cell death when expressed in the yeast Saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    Van Rossom, Sofie; Op de Beeck, Ken; Franssens, Vanessa; Swinnen, Erwin; Schepers, Anne; Ghillebert, Ruben; Caldara, Marina; Van Camp, Guy; Winderickx, Joris

    2012-01-01

    DFNA5 was first identified as a gene responsible for autosomal dominant deafness. Different mutations were found, but they all resulted in exon 8 skipping during splicing and premature termination of the protein. Later, it became clear that the protein also has a tumor suppression function and that it can induce apoptosis. Epigenetic silencing of the DFNA5 gene is associated with different types of cancers, including gastric and colorectal cancers as well as breast tumors. We introduced the wild-type and mutant DFNA5 allele in the yeast Saccharomyces cerevisiae. The expression of the wild-type protein was well tolerated by the yeast cells, although the protein was subject of degradation and often deposited in distinct foci when cells entered the diauxic shift. In contrast, cells had problems to cope with mutant DFNA5 and despite an apparent compensatory reduction in expression levels, the mutant protein still triggered a marked growth defect, which in part can be ascribed to its interaction with mitochondria. Consistently, cells with mutant DFNA5 displayed significantly increased levels of ROS and signs of programmed cell death. The latter occurred independently of the yeast caspase, Mca1, but involved the mitochondrial fission protein, Fis1, the voltage-dependent anion channel protein, Por1 and the mitochondrial adenine nucleotide translocators, Aac1 and Aac3. Recent data proposed DFNA5 toxicity to be associated to a globular domain encoded by exon 2–6. We confirmed these data by showing that expression of solely this domain confers a strong growth phenotype. In addition, we identified a point mutant in this domain that completely abrogated its cytotoxicity in yeast as well as human Human Embryonic Kidney 293T cells (HEK293T). Combined, our data underscore that the yeast system offers a valuable tool to further dissect the apoptotic properties of DFNA5.

  6. The splicing mutant of the human tumor suppressor protein DFNA5 induces programmed cell death when expressed in the yeast Saccharomyces cerevisiae

    Energy Technology Data Exchange (ETDEWEB)

    Van Rossom, Sofie [Department of Biology, Functional Biology, KU Leuven, Leuven-Heverlee (Belgium); Department of Biomedical Sciences, Center of Medical Genetics, University of Antwerp, Wilrijk-Antwerp (Belgium); Op de Beeck, Ken [Department of Biomedical Sciences, Center of Medical Genetics, University of Antwerp, Wilrijk-Antwerp (Belgium); Franssens, Vanessa; Swinnen, Erwin [Department of Biology, Functional Biology, KU Leuven, Leuven-Heverlee (Belgium); Schepers, Anne [Department of Biomedical Sciences, Center of Medical Genetics, University of Antwerp, Wilrijk-Antwerp (Belgium); Ghillebert, Ruben; Caldara, Marina [Department of Biology, Functional Biology, KU Leuven, Leuven-Heverlee (Belgium); Van Camp, Guy [Department of Biomedical Sciences, Center of Medical Genetics, University of Antwerp, Wilrijk-Antwerp (Belgium); Winderickx, Joris, E-mail: guy.vancamp@ua.ac.be, E-mail: joris.winderickx@bio.kuleuven.be [Department of Biology, Functional Biology, KU Leuven, Leuven-Heverlee (Belgium)

    2012-07-25

    DFNA5 was first identified as a gene responsible for autosomal dominant deafness. Different mutations were found, but they all resulted in exon 8 skipping during splicing and premature termination of the protein. Later, it became clear that the protein also has a tumor suppression function and that it can induce apoptosis. Epigenetic silencing of the DFNA5 gene is associated with different types of cancers, including gastric and colorectal cancers as well as breast tumors. We introduced the wild-type and mutant DFNA5 allele in the yeast Saccharomyces cerevisiae. The expression of the wild-type protein was well tolerated by the yeast cells, although the protein was subject of degradation and often deposited in distinct foci when cells entered the diauxic shift. In contrast, cells had problems to cope with mutant DFNA5 and despite an apparent compensatory reduction in expression levels, the mutant protein still triggered a marked growth defect, which in part can be ascribed to its interaction with mitochondria. Consistently, cells with mutant DFNA5 displayed significantly increased levels of ROS and signs of programmed cell death. The latter occurred independently of the yeast caspase, Mca1, but involved the mitochondrial fission protein, Fis1, the voltage-dependent anion channel protein, Por1 and the mitochondrial adenine nucleotide translocators, Aac1 and Aac3. Recent data proposed DFNA5 toxicity to be associated to a globular domain encoded by exon 2–6. We confirmed these data by showing that expression of solely this domain confers a strong growth phenotype. In addition, we identified a point mutant in this domain that completely abrogated its cytotoxicity in yeast as well as human Human Embryonic Kidney 293T cells (HEK293T). Combined, our data underscore that the yeast system offers a valuable tool to further dissect the apoptotic properties of DFNA5.

  7. DMPD: LPS induction of gene expression in human monocytes. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 11257452 LPS induction of gene expression in human monocytes. Guha M, Mackman N. Ce...ll Signal. 2001 Feb;13(2):85-94. (.png) (.svg) (.html) (.csml) Show LPS induction of gene expression in human... monocytes. PubmedID 11257452 Title LPS induction of gene expression in human monocytes. Authors Guha M, Ma

  8. [Outcomes of surgical management of retinopathy of prematurity--an overview].

    Science.gov (United States)

    Kuprjanowicz, Leszek; Kubasik-Kładna, Katarzyna; Modrzejewska, Monika

    2014-01-01

    According to the guidelines by the ETROP (Early Treatment for Retinopathy of Prematurity) study group, laser therapy is the gold standard in the treatment of retinopathy of prematurity. However, progression of the disease is seen in 12% of eyes despite the treatment. Since there is no causal treatment, new therapies of retinopathy of prematurity, are continually sought, such as anti-VEGF agents, beta-blockers, or insulin-like growth factor gene therapy. In cases with concomitant retinal detachment, surgery is performed. The standard therapy for retinopathy of prematurity stages 4-5 involves pars plicata vitrectomy and lensectomy (stage 5), ab externo surgery (scleral buckling) and lens-sparing vitrectomy (some cases of stage 4). Classic vitrectomy with lensectomy is reserved only for cases with advanced retinal tractions, retina-lens apposition or for cases of intraoperative lens damage during the lens-sparing vitrectomy. The ab externo surgery does not eliminate vitreous tractions, but it stabilises the neovascular membrane activity (transforming it into a scar). The indication for this type of operation is stage 4 retinopathy of prematurity with peripheral proliferations, except for the posterior--aggressive form of retinopathy of prematurity. Many papers have been published on combined therapy involving vitrectomy and conservative treatment. In conclusion, optimal timing of surgical intervention is difficult to determine in stages 4 and 5, because the anatomical and functional outcomes in stage 5 are unfavourable. Both, ab externo surgery and vitrectomy tend to produce poor macular vision in eyes with advanced retinopathy of prematurity, therefore surgical intervention at stage 4 just before the local macular retinal detachment provides better anatomical and functional outcomes.

  9. Biomarkers of brain injury in the premature infant

    Directory of Open Access Journals (Sweden)

    Martha V. Douglas-Escobar

    2013-01-01

    Full Text Available The term encephalopathy of prematurity encompasses not only the acute brain injury (such as intraventricular hemorrhage but also complex disturbance on the infant’s subsequent brain development. In premature infants, the most frequent recognized source of brain injury is intraventricular hemorrhage (IVH and periventricular leukomalacia (PVL. Furthermore 20-25% infants with birth weigh less than 1,500 g will have IVH and that proportion increases to 45% if the birth weight is less than 500-750 g. In addition, nearly 60% of very low birth weight newborns will have hypoxic-ischemic injury. Therefore permanent lifetime neurodevelopmental disabilities are frequent in premature infants. Innovative approach to prevent or decrease brain injury in preterm infants requires discovery of biomarkers able to discriminate infants at risk for injury, monitor the progression of the injury and assess efficacy of neuroprotective clinical trials. In this article, we will review biomarkers studied in premature infants with IVH, Post-hemorrhagic ventricular dilation (PHVD and PVL including: S100b, Activin A, erythropoietin, chemokine CCL 18, GFAP and NFL will also be examined. Some of the most promising biomarkers for IVH are S100β and Activin. The concentrations of TGF-β1, MMP-9 and PAI-1 in cerebrospinal fluid could be used to discriminate patients that will require shunt after post-hemorrhagic ventricular dilation. Neonatal brain injury is frequent in premature infants admitted to the neonatal intensive care and we hope to contribute to the awareness and interest in clinical validation of established as well as novel neonatal brain injury biomarkers.

  10. Impact of Prematurity on Language Skills at School Age

    Science.gov (United States)

    Smith, Jamie Mahurin; DeThorne, Laura Segebart; Logan, Jessica A. R.; Channell, Ron W.; Petrill, Stephen A.

    2014-01-01

    Purpose: The existing literature on language outcomes in children born prematurely focuses almost exclusively on standardized test scores rather than discourse-level abilities. The authors of this study looked longitudinally at school-age language outcomes and potential moderating variables for a group of twins born prematurely versus a control…

  11. Effect of enteral IGF-1 supplementation on feeding tolerance, growth, and gut permeability in enterally fed premature neonates

    NARCIS (Netherlands)

    Corpeleijn, Willemijn E.; van Vliet, Ineke; de Gast-Bakker, Dana-Anne H.; van der Schoor, Sophie R. D.; Alles, Martine S.; Hoijer, Maarten; Tibboel, Dick; van Goudoever, Johannes B.

    2008-01-01

    The gastrointestinal tract of the premature newborn functions suboptimally with regard to digestion, absorption, and feeding tolerance. Human milk contains trophic factors, such as insulin-like growth factor-1 (IGF-1), that are believed to stimulate gut growth and function. The objective of this

  12. Advances in understanding and management of retinopathy of prematurity.

    Science.gov (United States)

    Hartnett, Mary Elizabeth

    The understanding, diagnosis, and treatment of retinopathy of prematurity have changed in the 70 years since the original description of retrolental fibroplasia associated with high oxygenation. It is now recognized that retinopathy of prematurity differs in appearance worldwide and as ever smaller and younger premature infants survive. New methods are being evaluated to image the retina, diagnose severe retinopathy of prematurity, and determine windows of time for treatment to save eyes and improve visual and neural outcomes. New treatments to promote physiologic retinal vascular development, vascular repair, and inhibit vasoproliferation by regulating proteins involved in vascular endothelial growth factor, insulin-like growth factor, or erythropoietin signaling. Reducing excessive oxidative/nitrosative stress and understanding progenitor cells and neurovascular and glial vascular interactions are being studied. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Subcellular localization of human neutral ceramidase expressed in HEK293 cells

    International Nuclear Information System (INIS)

    Hwang, Young-ha; Tani, Motohiro; Nakagawa, Tetsuto; Okino, Nozomu; Ito, Makoto

    2005-01-01

    We previously reported that rat and mouse neutral ceramidases were mainly localized to plasma membranes as a type II integral membrane protein and partly detached from the cells via processing of the N-terminal/anchor sequence when expressed in HEK293 cells [M. Tani, H. Iida, M. Ito, O-glycosylation of mucin-like domain retains the neutral ceramidase on the plasma membranes as a type II integral membrane protein, J. Biol. Chem. 278 (2003) 10523-10530]. In contrast, the human homologue was exclusively detected in mitochondria when expressed in HEK293 and MCF7 cells as a fusion protein with green fluorescent protein at the N-terminal of the enzyme [S.E. Bawab, P. Roddy, T. Quian, A. Bielawska, J.J. Lemasters, Y.A. Hannun, Molecular cloning and characterization of a human mitochondrial ceramidase, J. Biol. Chem. 275 (2000) 21508-21513]. Given this discrepancy, we decided to clone the neutral ceramidase from human kidney cDNA and re-examine the intracellular localization of the enzyme when expressed in HEK293 cells. The putative amino acid sequence of the newly cloned enzyme was identical to that reported for human neutral ceramidase except at the N-terminal; the new protein was 19 amino acids longer at the N-terminal. We found that the putative full-length human neutral ceramidase was transported to plasma membranes, but not to mitochondria, possibly via a classical ER/Golgi pathway and localized mainly in plasma membranes when expressed in HEK293 cells. The N-terminal-truncated mutant, previously reported as a human mitochondrial ceramidase, was also weakly expressed in HEK293 cells but mainly released into the medium possibly due to the insufficient signal/anchor sequence

  14. HEARING FUNCTION IN PREMATURE CHILDREN WITH INTRAUTERINE GROWTH RESTRICTION

    Directory of Open Access Journals (Sweden)

    I. V. Rakhmanova

    2012-01-01

    Full Text Available Initial audiological test was performed in 136 premature children with various gestational age born from single fetation. The children were divided into 2 groups: prematures with intrauterine growth restriction (IUGR and prematures with normal weight for their gestational age (normotrophy. The study showed that the rate of passing the initial audiological test using the method of DPOAE was lower in both ears in children with IUGR, than in children with normotrophy. The correlation between the results of initial audiological test and birth weight was found: the lower was weight, the higher was risk of absence of acoustic response registration on initial examination.

  15. A NANOS3 mutation linked to protein degradation causes premature ovarian insufficiency

    OpenAIRE

    Wu, X; Wang, B; Dong, Z; Zhou, S; Liu, Z; Shi, G; Cao, Y; Xu, Y

    2013-01-01

    Primary ovarian insufficiency (POI), or premature ovarian failure, is defined as the cessation of ovarian function before the age of 40. An insufficient ovarian follicle pool derived from primordial germ cells (PGCs) is an important cause of POI. Although the Nanos gene family is known to be required for PGC development and maintenance in diverse model organisms, the relevance of this information to human biology is not yet clear. In this study, we screened the coding regions of the NANOS1, N...

  16. Importance of the brow in facial expressiveness during human communication.

    Science.gov (United States)

    Neely, John Gail; Lisker, Paul; Drapekin, Jesse

    2014-03-01

    The objective of this study was to evaluate laterality and upper/lower face dominance of expressiveness during prescribed speech using a unique validated image subtraction system capable of sensitive and reliable measurement of facial surface deformation. Observations and experiments of central control of facial expressions during speech and social utterances in humans and animals suggest that the right mouth moves more than the left during nonemotional speech. However, proficient lip readers seem to attend to the whole face to interpret meaning from expressed facial cues, also implicating a horizontal (upper face-lower face) axis. Prospective experimental design. Experimental maneuver: recited speech. image-subtraction strength-duration curve amplitude. Thirty normal human adults were evaluated during memorized nonemotional recitation of 2 short sentences. Facial movements were assessed using a video-image subtractions system capable of simultaneously measuring upper and lower specific areas of each hemiface. The results demonstrate both axes influence facial expressiveness in human communication; however, the horizontal axis (upper versus lower face) would appear dominant, especially during what would appear to be spontaneous breakthrough unplanned expressiveness. These data are congruent with the concept that the left cerebral hemisphere has control over nonemotionally stimulated speech; however, the multisynaptic brainstem extrapyramidal pathways may override hemiface laterality and preferentially take control of the upper face. Additionally, these data demonstrate the importance of the often-ignored brow in facial expressiveness. Experimental study. EBM levels not applicable.

  17. Gene Expression in the Human Endolymphatic Sac

    DEFF Research Database (Denmark)

    Møller, Martin Nue; Kirkeby, Svend; Vikeså, Jonas

    2015-01-01

    a1 sodium-bicarbonate transporter, SLC9a2 sodium-hydrogen transporter, SLC12a3 thiazide-sensitive Na-Cl transporter, and SLC34a2 sodium-phosphate transporter. CONCLUSIONS: Several important ion transporters of the SLC family are expressed in the human endolymphatic sac, including Pendrin...

  18. Onco-GPCR signaling and dysregulated expression of microRNAs in human cancer.

    Science.gov (United States)

    Nohata, Nijiro; Goto, Yusuke; Gutkind, J Silvio

    2017-01-01

    The G-protein-coupled receptor (GPCR) family is the largest family of cell-surface receptors involved in signal transduction. Aberrant expression of GPCRs and G proteins are frequently associated with prevalent human diseases, including cancer. In fact, GPCRs represent the therapeutic targets of more than a quarter of the clinical drugs currently on the market. MiRNAs (miRNAs) are also aberrantly expressed in many human cancers, and they have significant roles in the initiation, development and metastasis of human malignancies. Recent studies have revealed that dysregulation of miRNAs and their target genes expression are associated with cancer progression. The emerging information suggests that miRNAs play an important role in the fine tuning of many signaling pathways, including GPCR signaling. We summarize our current knowledge of the individual functions of miRNAs regulated by GPCRs and GPCR signaling-associated molecules, and miRNAs that regulate the expression and activity of GPCRs, their endogenous ligands and their coupled heterotrimeric G proteins in human cancer.

  19. Intestinal Microbiota in Premature Children — the Modern State of the Problem (Literature Analysis

    Directory of Open Access Journals (Sweden)

    I. A. Belyaeva

    2015-01-01

    Full Text Available The problem of intestinal microbiota influencing the health of early aged children has become especially relevant over the past few years. On one hand, this is due to the significant worsening of the human environment ecology, on the other — due to the high prevalence of digestive disorders in children, especially premature ones. The introduction of modern high-informative molecular-genetic research methods (PCR-amplification with gene sequenation made it possible to reveal the primary stage of human colonization by bacteria even at the stage of fetal ontogenesis and to thoroughly decode the microbiota structure in newborns and first-year babies. It is established, that the mothers microbiota has a direct effect on the quantity and quality of the child’s microbiota. The mother’s microbiota depends not only on her possessing inflammatory, but also metabolic diseases (obesity. There is also a direct correlation between the children’s microbiota and the wway they were born (microbiota is better in cases of natural birth, and these differences are prevalent after a number of months after birth. One of the main factors affecting microbiota after birth from the very first day is nutrition. Most studies earnestly confirm the role of breastfeeding in contributing to an optimal microbiocenosis in the child. Antibacterial therapy, being received by either the mother or the child has a negative effect on the colonization of the intestines by symbiont microbes. The negative impacts on the micro flora are especially significant for premature children especially those born with a very low and extremely low body mass. The ontogenesis of these children is most severed by malicious factors (infections followed by the necessity of a massive antibacterial therapy, hypoxia, surgical birth, forced artificial feeding in connection with a general immaturity, including not yet fully-fledged body defense systems. Directive microbiota correction in premature

  20. [Cloning of human CD45 gene and its expression in Hela cells].

    Science.gov (United States)

    Li, Jie; Xu, Tianyu; Wu, Lulin; Zhang, Liyun; Lu, Xiao; Zuo, Daming; Chen, Zhengliang

    2015-11-01

    To clone human CD45 gene PTPRC and establish Hela cells overexpressing recombinant human CD45 protein. The intact cDNA encoding human CD45 amplified using RT-PCR from the total RNA extracted from peripheral blood mononuclear cells (PBMCs) of a healthy donor was cloned into pMD-18T vector. The CD45 cDNA fragment amplified from the pMD-18T-CD45 by PCR was inserted to the coding region of the PcDNA3.1-3xflag vector, and the resultant recombinant expression vector PcDNA3.1-3xflag-CD45 was transfected into Hela cells. The expression of CD45 in Hela cells was detected by flow cytometry and Western blotting, and the phosphastase activity of CD45 was quantified using an alkaline phosphatase assay kit. The cDNA fragment of about 3 900 bp was amplified from human PBMCs and cloned into pMD-18T vector. The recombinant expression vector PcDNA3.1-3xflag-CD45 was constructed, whose restriction maps and sequence were consistent with those expected. The expression of CD45 in transfected Hela cells was detected by flow cytometry and Western blotting, and the expressed recombinant CD45 protein in Hela cells showed a phosphastase activity. The cDNA of human CD45 was successfully cloned and effectively expressed in Hela cells, which provides a basis for further exploration of the functions of CD45.

  1. Histological Chorioamnionitis: Effects on Premature Delivery and Neonatal Prognosis

    Directory of Open Access Journals (Sweden)

    Gulin Erdemir

    2013-08-01

    Conclusion: Chorioamnionitis not only causes premature deliveries, but is also associated with neonatal complications and increased mortality. Clinical findings and infectious markers in mother or infant do not predict the diagnosis of histological chorioamnionitis. Therefore, placental histopathology may have a role in predicting neonatal outcome in premature deliveries, especially those below 30 weeks.

  2. Expression of a novel cardiac-specific tropomyosin isoform in humans

    International Nuclear Information System (INIS)

    Denz, Christopher R.; Narshi, Aruna; Zajdel, Robert W.; Dube, Dipak K.

    2004-01-01

    Tropomyosins are a family of actin binding proteins encoded by a group of highly conserved genes. Humans have four tropomyosin-encoding genes: TPM1, TPM2, TPM3, and TPM4, each of which is known to generate multiple isoforms by alternative splicing, promoters, and 3 ' end processing. TPM1 is the most versatile and encodes a variety of tissue specific isoforms. The TPM1 isoform specific to striated muscle, designated TPM1α, consists of 10 exons: 1a, 2b, 3, 4, 5, 6b, 7, 8, and 9a/b. In this study, using RT-PCR with adult and fetal human RNAs, we present evidence for the expression of a novel isoform of the TPM1 gene that is specifically expressed in cardiac tissues. The new isoform is designated TPM1κ and contains exon 2a instead of 2b. Ectopic expression of human GFP.TPM1κ fusion protein can promote myofibrillogenesis in cardiac mutant axolotl hearts that are lacking in tropomyosin

  3. Social representations of mothers about gestational hypertension and premature birth.

    Science.gov (United States)

    de Souza, Nilba Lima; de Araújo, Ana Cristina Pinheiro Fernandes; Costa, Iris do Ceu Clara

    2013-01-01

    To identify the meanings attributed by mothers to hypertensive disorders of pregnancy (HDPs) and their consequences, such as premature birth and hospitalization of the infant in the neonatal intensive care unit (NICU). A qualitative study, based on the Central Nucleus Theory, with 70 women who had hypertensive disorders of pregnancy and preterm delivery. We used the technique of free word association (FWAT) with three stimuli: high blood pressure during pregnancy, prematurity and NICU. We obtained 1007 evocations, distributed as follows: high blood pressure during pregnancy (335) prematurity (333) and NICU (339). These constituted three thematic units: representation of HDPs, prematurity and the NICU. The categories death and negative aspects were inherent to the three units analyzed, followed by coping strategies and needs for care present in HDPs and prematurity. The study had death as its central nucleus, and highlighted the subjective aspects present in the high risk pregnancy and postpartum cycle. It is hoped that this research will contribute to qualifying nursing care for women confronting the problem of HDPs, so that they can cope with less impacts from the adverse effects of high risk pregnancy and birth.

  4. Systematic analysis of gene expression patterns associated with postmortem interval in human tissues.

    Science.gov (United States)

    Zhu, Yizhang; Wang, Likun; Yin, Yuxin; Yang, Ence

    2017-07-14

    Postmortem mRNA degradation is considered to be the major concern in gene expression research utilizing human postmortem tissues. A key factor in this process is the postmortem interval (PMI), which is defined as the interval between death and sample collection. However, global patterns of postmortem mRNA degradation at individual gene levels across diverse human tissues remain largely unknown. In this study, we performed a systematic analysis of alteration of gene expression associated with PMI in human tissues. From the Genotype-Tissue Expression (GTEx) database, we evaluated gene expression levels of 2,016 high-quality postmortem samples from 316 donors of European descent, with PMI ranging from 1 to 27 hours. We found that PMI-related mRNA degradation is tissue-specific, gene-specific, and even genotype-dependent, thus drawing a more comprehensive picture of PMI-associated gene expression across diverse human tissues. Additionally, we also identified 266 differentially variable (DV) genes, such as DEFB4B and IFNG, whose expression is significantly dispersed between short PMI (S-PMI) and long PMI (L-PMI) groups. In summary, our analyses provide a comprehensive profile of PMI-associated gene expression, which will help interpret gene expression patterns in the evaluation of postmortem tissues.

  5. Radiation-induced life-shortening and premature aging

    International Nuclear Information System (INIS)

    Walburg, H.E. Jr.

    1975-01-01

    Data from a number of studies on irradiated laboratory animals showed that almost none of the characteristic lesions associated with senescence that were studied adequately reflects a radiation effect analogous to premature aging. In fact, most of the age-related changes showed no effect of radiation at all, and many of those that did (for example, graying of hair, sterility, cataract formation) did not appear to be due to similar mechanisms. It is concluded that, in the light of more recent information, the hypothesis of radiation-induced premature aging requires reassessment. (80 references) (CH)

  6. Human trabecular meshwork cells express BMP antagonist mRNAs and proteins.

    Science.gov (United States)

    Tovar-Vidales, Tara; Fitzgerald, Ashley M; Clark, Abbot F

    2016-06-01

    Glaucoma patients have elevated aqueous humor and trabecular meshwork (TM) levels of transforming growth factor-beta2 (TGF-β2). TGF-β2 has been associated with increased extracellular matrix (ECM) deposition (i.e. fibronectin), which is attributed to the increased resistance of aqueous humor outflow through the TM. We have previously demonstrated that bone morphogenetic protein (BMP) 4 selectively counteracts the profibrotic effect of TGF-β2 with respect to ECM synthesis in the TM, and this action is reversed by the BMP antagonist gremlin. Thus, the BMP and TGF-β signaling pathways antagonize each other's antifibrotic and profibrotic roles. The purpose of this study was to determine whether cultured human TM cells: (a) express other BMP antagonists including noggin, chordin, BMPER, BAMBI, Smurf1 and 2, and (b) whether expression of these proteins is regulated by exogenous TGF-β2 treatment. Primary human trabecular meshwork (TM) cells were grown to confluency and treated with TGF-β2 (5 ng/ml) for 24 or 48 h in serum-free medium. Untreated cell served as controls. qPCR and Western immunoblots (WB) determined that human TM cells expressed mRNAs and proteins for the BMP antagonist proteins: noggin, chordin, BMPER, BAMBI, and Smurf1/2. Exogenous TGF-β2 decreased chordin, BMPER, BAMBI, and Smurf1 mRNA and protein expression. In contrast, TGF-β2 increased secreted noggin and Smurf2 mRNA and protein levels. BMP antagonist members are expressed in the human TM. These molecules may be involved in the normal function of the TM as well as TM pathogenesis. Altered expression of BMP antagonist members may lead to functional changes in the human TM. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Expression of fully functional tetrameric human hemoglobin in Escherichia coli

    International Nuclear Information System (INIS)

    Hoffman, S.J.; Looker, D.L.; Roehrich, J.M.; Cozart, P.E.; Durfee, S.L.; Tedesco, J.L.; Stetler, G.L.

    1990-01-01

    Synthesis genes encoding the human α- and β-globin polypeptides have been expressed from a single operon in Escherichia coli. The α- and β-globin polypeptides associate into soluble tetramers, incorporate heme, and accumulate to >5% of the total cellular protein. Purified recombinant hemoglobin has the correct stoichiometry of α- and β-globin chains and contains a full complement of heme. Each globin chain also contains an additional methionine as an extension to the amino terminus. The recombinant hemoglobin has a C 4 reversed-phase HPLC profile essentially identical to that of human hemoglobin A 0 and comigrates with hemoglobin A 0 on SDS/PAGE. The visible spectrum and oxygen affinity are similar to that of native human hemoglobin A 0 . The authors have also expressed the α- and β-globin genes separately and found that the expression of the α-globin gene alone results in a marked decrease in the accumulation of α-globin in the cell. Separate expression of the β-globin gene results in high levels of insoluble β-globin. These observations suggest that the presence of α- and β-globin in the same cell stabilizes α-globin and aids the correct folding of β-globin. This system provides a simple method for expressing large quantities of recombinant hemoglobin and allows facile manipulation of the genes encoding hemoglobin to produce functionally altered forms of this protein

  8. Intrauterine growth restriction and prematurity influence regulatory T cell development in newborns.

    Science.gov (United States)

    Mukhopadhyay, Dhriti; Weaver, Laura; Tobin, Richard; Henderson, Stephanie; Beeram, Madhava; Newell-Rogers, M Karen; Perger, Lena

    2014-05-01

    The aim of this study was to determine the relationship of birth weight and gestational age with regulatory T cells (Tregs) in cord blood of human newborns. Cord blood mononuclear cells (CBMCs) of 210 newborns were analyzed using flow cytometry to identify Tregs (CD3(+), CD4(+), CD25(high), FoxP3(high)) and measure FoxP3 mean fluorescence intensity (MFI). Suppressive index (SI) was calculated as FoxP3 MFI per Treg. Mode of delivery had no significant effect on Tregs at birth. Term babies with growth restriction had fewer Tregs than their appropriate weight counterparts but equivalent SI. Preterm babies had higher percentages of Tregs, but lower SI than term controls. SI steadily increased through gestation. Intrauterine growth restriction is correlated with fewer circulating Tregs and prematurity with decreased functionality of Tregs compared to term appropriate weight infants. This may have implications in diseases such as necrotizing enterocolitis that disproportionately affect premature and lower birth weight infants. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Features of retinopathy of prematurity in a tertiary care hospital in Lahore.

    Science.gov (United States)

    Jamil, Ahmad Zeeshan; Tahir, Muhammad Younis; Ayub, Muhammad Hammad; Mirza, Khurram Azam

    2015-02-01

    To study the demographic and clinical features of Retinopathy of Prematurity in urban Punjab. The cross-sectional study was performed at Hameed Latif Hospital, Lahore, from April 2010 to October 2013 and comprised neonates born with birth weight less than 2000 g, gestational age less than 37 weeks, or those who were considered high risk for Retinopathy of Prematurity. Variables recorded included history, birth weight, gestational age, oxygen supplementation, development of Retinopathy of Prematurity, and laser treatment. Data was analysed using SPSS 17. There were 285 neonates in the study with a mean birth weight of 1280.34 ± 350.43 g and mean gestational age being 29.38 ± 3.14 weeks. Overall, 167 (58.6%) received supplemental oxygen, 86(30.2%) were anaemic and 44 (15.4%) received blood transfusion. Besides, 47 (16.5%) premature babies were product of multiple gestation, 34 (11.9%) were having respiratory distress, 25 (8.8%) had sepsis and received intravenous antibiotics, 70(24.6%) developed Retinopathy of Prematurity, and 22 (7.7%) developed threshold disease and received laser treatment at mean gestational age of 32.11 ± 2.53 weeks. Screening is key to preventing childhood blindness caused by Retinopathy of Prematurity. Prematurity, low birth weight and supplemental oxygen therapy are significant risk factors for the condition.

  10. PKCα expression regulated by Elk-1 and MZF-1 in human HCC cells

    International Nuclear Information System (INIS)

    Hsieh, Y.-H.; Wu, T.-T.; Tsai, J.-H.; Huang, C.-Y.; Hsieh, Y.-S.; Liu, J.-Y.

    2006-01-01

    Our previous study found that PKCα was highly expressed in the poor-differentiated human HCC cells and associated with cell migration and invasion. In this study, we further investigated the gene regulation of this enzyme. We showed that PKCα expression enhancement in the poor-differentiated human HCC cells was found neither by DNA amplification nor by increasing mRNA stability using differential PCR and mRNA decay assays. After screening seven transcription factors in the putative cis-acting regulatory elements of human PKCα promoters, only Elk-1 and MZF-1 antisense oligonucleotide showed a significant reduction in the PKCα mRNA level. They also reduced cell proliferation, cell migratory and invasive capabilities, and DNA binding activities in the PKCα promoter region. Over-expression assay confirmed that the PKCα expression may be modulated by these two factors at the transcriptional level. Therefore, these results may provide a novel mechanism for PKCα expression regulation in human HCC cells

  11. Risk factors of intracranial hemorrhage in premature neonates.

    Directory of Open Access Journals (Sweden)

    Nasrin Khalessi

    2014-09-01

    Full Text Available Intraventricular hemorrhage (IVH is an important cause of brain injury in premature neonates. Current study tries to define associated risk factors of IVH in preterm neonates in Aliasghar Children Hospital during 2008 to 2011. In this study, the risk factors have been evaluated in premature neonates with IVH, who had at least one brain sonography since their admission in NICU. A total of 63 premature neonates with IVH were assessed. Mean gestational age was 29.81 (24-34 weeks and mean birth weight was 1290.83±382.96 gr. Other risk factors such as sex, mode of delivery, history of using infertility drugs, maternal disease, maternal hypertension and preeclampsia, lumbar puncture, ventilator therapy and pneumothorax were considered. Because no absolute treatment for IVH is available, identifying risk factors is important in prevention and management of IVH.

  12. Neurological consequences of systemic inflammation in the premature neonate.

    Science.gov (United States)

    Patra, Aparna; Huang, Hong; Bauer, John A; Giannone, Peter J

    2017-06-01

    Despite substantial progress in neonatal care over the past two decades leading to improved survival of extremely premature infants, extreme prematurity continues to be associated with long term neurodevelopmental impairments. Cerebral white matter injury is the predominant form of insult in preterm brain leading to adverse neurological consequences. Such brain injury pattern and unfavorable neurologic sequelae is commonly encountered in premature infants exposed to systemic inflammatory states such as clinical or culture proven sepsis with or without evidence of meningitis, prolonged mechanical ventilation, bronchopulmonary dysplasia, necrotizing enterocolitis and chorioamnionitis. Underlying mechanisms may include cytokine mediated processes without direct entry of pathogens into the brain, developmental differences in immune response and complex neurovascular barrier system that play a critical role in regulating the cerebral response to various systemic inflammatory insults in premature infants. Understanding of these pathologic mechanisms and clinical correlates of such injury based on serum biomarkers or brain imaging findings on magnetic resonance imaging will pave way for future research and translational therapeutic opportunities for the developing brain.

  13. Neurological consequences of systemic inflammation in the premature neonate

    Directory of Open Access Journals (Sweden)

    Aparna Patra

    2017-01-01

    Full Text Available Despite substantial progress in neonatal care over the past two decades leading to improved survival of extremely premature infants, extreme prematurity continues to be associated with long term neurodevelopmental impairments. Cerebral white matter injury is the predominant form of insult in preterm brain leading to adverse neurological consequences. Such brain injury pattern and unfavorable neurologic sequelae is commonly encountered in premature infants exposed to systemic inflammatory states such as clinical or culture proven sepsis with or without evidence of meningitis, prolonged mechanical ventilation, bronchopulmonary dysplasia, necrotizing enterocolitis and chorioamnionitis. Underlying mechanisms may include cytokine mediated processes without direct entry of pathogens into the brain, developmental differences in immune response and complex neurovascular barrier system that play a critical role in regulating the cerebral response to various systemic inflammatory insults in premature infants. Understanding of these pathologic mechanisms and clinical correlates of such injury based on serum biomarkers or brain imaging findings on magnetic resonance imaging will pave way for future research and translational therapeutic opportunities for the developing brain.

  14. SORBS2 and TLR3 induce premature senescence in primary human fibroblasts and keratinocytes

    International Nuclear Information System (INIS)

    Liesenfeld, Melanie; Mosig, Sandy; Funke, Harald; Jansen, Lars; Runnebaum, Ingo B; Dürst, Matthias; Backsch, Claudia

    2013-01-01

    Genetic aberrations are required for the progression of HPV-induced cervical precancers. A prerequisite for clonal expansion of cancer cells is unlimited proliferative capacity. In a cell culture model for cervical carcinogenesis loss of genes located on chromosome 4q35→qter and chromosome 10p14-p15 were found to be associated with escape from senescence. Moreover, by LOH and I-FISH analyses a higher frequency of allele loss of these regions was also observed in cervical carcinomas as compared to CIN3. The aim of this study was to identify candidate senescence-related genes located on chromosome 4q35→qter and chromosome 10p14-p15 which may contribute to clonal expansion at the transition of CIN3 to cancer. Microarray expression analyses were used to identify candidate genes down-regulated in cervical carcinomas as compared to CIN3. In order to relate these genes with the process of senescence their respective cDNAs were overexpressed in HPV16-immortalized keratinocytes as well as in primary human fibroblasts and keratinocytes using lentivirus mediated gene transduction. Overall fifteen genes located on chromosome 4q35→qter and chromosome 10p14-p15 were identified. Ten of these genes could be validated in biopsies by RT-PCR. Of interest is the novel finding that SORBS2 and TLR3 can induce senescence in primary human fibroblasts and keratinocytes but not in HPV-immortalized cell lines. Intriguingly, the endogenous expression of both genes increases during finite passaging of primary keratinocytes in vitro. The relevance of the genes SORBS2 and TLR3 in the process of cellular senescence warrants further investigation. In ongoing experiments we are investigating whether this increase in gene expression is also characteristic of replicative senescence

  15. Pathophysiology of gastroesophageal reflux disease in premature infants using a radionuclide method

    International Nuclear Information System (INIS)

    Ishihara, Michiomi

    2001-01-01

    The cases of 36 very low birthweight infants (premature group) and 52 mature infants with birth weights as low as 1500 g (mature group) with gastro-esephageal reflux disease (GERD) were reviewed. These infants received 24 hour pH monitoring, reflux scintigraphy, gastric emptying, and antrum motility measurement. The results of 24-hour pH monitoring of the premature group are not different from these of the mature group. Time required for reflux scintigraphy of the premature group is higher than that of the mature group. Emptying time of premature group is slower than that of the mature group. Dietary management in premature infants with GERD is important. Using a nasoduodenal feeding tube is quite effective. Radionuclide method, in addition to 24-hour pH monitoring, should be used to evaluate total gastroesophageal function. (author)

  16. Pathophysiology of gastroesophageal reflux disease in premature infants using a radionuclide method

    Energy Technology Data Exchange (ETDEWEB)

    Ishihara, Michiomi [Tokyo Metropolitan Hospital of Ohkubo (Japan)

    2001-12-01

    The cases of 36 very low birthweight infants (premature group) and 52 mature infants with birth weights as low as 1500 g (mature group) with gastro-esephageal reflux disease (GERD) were reviewed. These infants received 24 hour pH monitoring, reflux scintigraphy, gastric emptying, and antrum motility measurement. The results of 24-hour pH monitoring of the premature group are not different from these of the mature group. Time required for reflux scintigraphy of the premature group is higher than that of the mature group. Emptying time of premature group is slower than that of the mature group. Dietary management in premature infants with GERD is important. Using a nasoduodenal feeding tube is quite effective. Radionuclide method, in addition to 24-hour pH monitoring, should be used to evaluate total gastroesophageal function. (author)

  17. Perspectives and attitudes of pediatricians concerning post-discharge care practice of premature infants.

    Science.gov (United States)

    Gad, A; Parkinson, E; Khawar, N; Elmeki, A; Narula, P; Hoang, D

    2017-01-01

    Survival rates of premature infants are at a historical high and increasingly more pediatricians are caring for former premature infants. The goal of this study was to describe the perspectives and attitudes of pediatricians, as well as, the challenges of rendering post-neonatal intensive care unit (NICU) discharge care for premature infants. An anonymous 22-question web-based survey was emailed to pediatricians who are current members of the American Academy of Pediatrics (AAP) and practicing in Kings County, New York. There were 148 completed surveys with 79% being general pediatricians. Of all respondents, 63% believed that premature infants should have a neonatal high risk follow-up visit within days after discharge and 64% were satisfied with the NICU discharge summary acquisition. While 74% of pediatricians felt comfortable following up with former extremely premature infants, 65% referred to specialists, most often to child development, neurology, and physical and/or occupational therapy. The majority (85%) were more likely to refer premature infants to early intervention. Participating pediatricians varied in their knowledge of immunization and breastfeeding guidelines. Finally, 88% of respondents acknowledged that caregivers of premature infants experience increased stress, with 53% stating that the stress should be addressed. Understanding the perceptions and challenges of pediatricians who care for premature infants may help improve post NICU quality of care. Transition to the outpatient setting is a crucial step in the management of premature infants and a focus on improved hand-off procedures between hospital and physicians may prove beneficial. Also, pediatricians must stay abreast of current recommendations for breastfeeding and vaccinations. Furthermore, emphasis should be given to stress reduction and management for caregivers of former premature infants.

  18. Differential expression gene profiling in human lymphocyte after 6 h irradiated

    International Nuclear Information System (INIS)

    Li Jianguo; Qin Xiujun; Zhang Wei; Xu Chaoqi; Li Weibin; Dang Xuhong; Zuo Yahui

    2011-01-01

    Objective: To provide the evidence of health damage for the staff irradiated from the gene level. Methods: The study analyzed the differential transcriptional profile of normal human lymphocyte and human lymphocyte irradiated with 0.1 Gy, 0.2 Gy, 0.5 Gy, 1.0 Gy by whole genome chip after 6 h irradiated. Results: The results showed that there were 1177 differentially expressed genes with 0.1 Gy after 6 h irradiation, and there were 1922 differentially expressed genes with 0.2 Gy after 6 h irradiation, and there were 492 differentially expressed genes with 0.5 Gy after 6 h irradiation, 2615 differentially expressed genes with 1.0 Gy after 6 h irradiation, 114 differentially expressed genes in 4 dose points after 6 h irradiation. RT-PCR results indicated that the relative quantity's result of EGR1, HLA-DMB and TAIAP1 was consistent with gene chip data. Conclusion: The study found many significant different genes in human lymphocyte with different doses after 6 h irradiation, which will provide a basis for the further radiation-different-genes and the mechanism of radiation damage. (authors)

  19. Influence of the blood glucose level on the development of retinopathy of prematurity in extremely premature children.

    Science.gov (United States)

    Nicolaeva, Galina V; Sidorenko, Evgenyj I; Iosifovna, Amkhanitskaya Lyubov

    2015-01-01

    To investigate the influence of the blood glucose level on the development of retinopathy of prematurity (ROP) in extremely premature infants. Sixty-four premature infants with a gestational age of less than 30 weeks and a birth weight of less than 1500 g were included in the study. Children without ROP were allocated to Group 1 (n=14, gestational age 28.6 ± 1.4 weeks, birth weight 1162 ± 322 g), and children with spontaneous regression of ROP were allocated to Group 2 (n=32, gestational age 26.5 ± 1.2 weeks, birth weight 905 ± 224 g). Children with progressive ROP who underwent laser treatment were included in Group 3 (n=18, gestational age 25.4 ± 0.7 weeks, birth weight 763 ± 138 g). The glucose level in the capillary blood of the premature infants was monitored daily during the first 3 weeks of life. A complete ophthalmological screening was performed from the age of 1 month. The nonparametric signed-rank Wilcoxon-Mann-Whitney test was used for statistical analysis. The mean blood glucose level was 7.43 ± 2.6 mmol/L in Group 1, 7.8 ± 2.7 mmol/L in Group 2, and 6.7 ± 2.6 mmol/L in Group 3. There were no significant differences in the blood glucose levels between children with and without ROP, and also between children with spontaneously regressing ROP and progressive ROP (p>0.05). Additionally, there were no significant differences in the blood glucose levels measured at the first, second, and third weeks of life (p>0.05). The blood glucose level is not related to the development of ROP nor with its progression or regression. The glycemic level cannot be considered as a risk factor for ROP, but reflects the severity of newborns' somatic condition and morphofunctional immaturity.

  20. Patent Ductus Arteriosus in Premature Neonates

    Science.gov (United States)

    Mezu-Ndubuisi, Olachi J.; Agarwal, Ghanshyam; Raghavan, Aarti; Pham, Jennifer T.; Ohler, Kirsten H.; Maheshwari, Akhil

    2015-01-01

    Persistent patency of the ductus arteriosus is a major cause of morbidity and mortality in premature infants. In infants born prior to 28 weeks of gestation, a hemodynamically-significant patent ductus arteriosus (PDA) can cause cardiovascular instability, exacerbate respiratory distress syndrome, prolong the need for assisted ventilation, and increase the risk of bronchopulmonary dysplasia, intraventricular hemorrhage, renal dysfunction, intraventricular hemorrhage, cerebral palsy, and mortality. In this article, we review the pathophysiology, clinical features, and assessment of hemodynamic significance, and provide a rigorous appraisal of the quality of evidence to support current medical and surgical management of PDA of prematurity. Cyclo-oxygenase inhibitors such as indomethacin and ibuprofen remain the mainstay of medical therapy for PDA, and can be used both for prophylaxis as well as rescue therapy to achieve PDA closure. Surgical ligation is also effective and is used in infants who do not respond to medical management. Although both medical and surgical treatment have proven efficacy in closing the ductus, both modalities are associated with significant adverse effects. Because the ductus does undergo spontaneous closure in some premature infants, improved and early identification of infants most likely to develop a symptomatic PDA could help in directing treatment to the at-risk infants and allow others to receive expectant management. PMID:22564132

  1. Hypoxic regulation of cytoglobin and neuroglobin expression in human normal and tumor tissues

    Directory of Open Access Journals (Sweden)

    Emara Marwan

    2010-09-01

    Full Text Available Abstract Background Cytoglobin (Cygb and neuroglobin (Ngb are recently identified globin molecules that are expressed in vertebrate tissues. Upregulation of Cygb and Ngb under hypoxic and/or ischemic conditions in vitro and in vivo increases cell survival, suggesting possible protective roles through prevention of oxidative damage. We have previously shown that Ngb is expressed in human glioblastoma multiforme (GBM cell lines, and that expression of its transcript and protein can be significantly increased after exposure to physiologically relevant levels of hypoxia. In this study, we extended this work to determine whether Cygb is also expressed in GBM cells, and whether its expression is enhanced under hypoxic conditions. We also compared Cygb and Ngb expression in human primary tumor specimens, including brain tumors, as well as in human normal tissues. Immunoreactivity of carbonic anhydrase IX (CA IX, a hypoxia-inducible metalloenzyme that catalyzes the hydration of CO2 to bicarbonate, was used as an endogenous marker of hypoxia. Results Cygb transcript and protein were expressed in human GBM cells, and this expression was significantly increased in most cells following 48 h incubation under hypoxia. We also showed that Cygb and Ngb are expressed in both normal tissues and human primary cancers, including GBM. Among normal tissues, Cygb and Ngb expression was restricted to distinct cell types and was especially prominent in ductal cells. Additionally, certain normal organs (e.g. stomach fundus, small bowel showed distinct regional co-localization of Ngb, Cygb and CA IX. In most tumors, Ngb immunoreactivity was significantly greater than that of Cygb. In keeping with previous in vitro results, tumor regions that were positively stained for CA IX were also positive for Ngb and Cygb, suggesting that hypoxic upregulation of Ngb and Cygb also occurs in vivo. Conclusions Our finding of hypoxic up-regulation of Cygb/Ngb in GBM cell lines and human

  2. [Initial results of the Erfurt Prevention of Prematurity Campaign].

    Science.gov (United States)

    Hoyme, U B; Grosch, A; Roemer, V M; Saling, E

    1998-01-01

    Genital infection particularly bacterial vaginosis (BV) increases the relative risk of prematurity. Detection of disturbances of vaginal milieu at an early stage and the use of suitable countermeasures such as intervention with antimicrobial substances, e.g. clindamycin, can reduce the preterm birth rate, provided the diagnosis is made early enough. Since October 1996 pregnant women being given prenatal care in 16 of the 29 outpatient offices in Erfurt, have been informed about the Prematurity Prevention Programme and have been offered to take part and to perform self-measurements of their vaginal pH twice a week in order to screen for any disturbances in the vaginal milieu. Special CarePlan-VpH gloves (Selfcare, Oberhaching) were used to identify patients a risk (pH > 4.7). The pregnant women taking part in the programme were instructed to see their physician immediately, if abnormal values were present, in order to get them confirmed and to start lactobacillus acidophilus therapy (Gynoflor, Nourypharma, Oberschleissheim) or, in case of BV, to treat with clindamycin cream (Sobelin, Upjohn, Erlangen) i.vag. Patients being given prenatal care in the 13 outpatient offices not participating and other pregnant women in Erfurt who were not interested in the programme served as control group. Up to now 59 out of 314 women in the intervention group have been identified as risk cases (p > or = 4.7). 52 of them were treated with a lactobacillus preparation, and 19 additionally with clindamycin cream, 3 patients refused to have any therapy. In this ongoing study the prematurity rate was 8.3% in the self-measurement/intervention group vs. 13.0% in the control group (n = 1,842); 0.3% vs. 3.3% of the neonates belonged to the group of very early prematures with a gestational age of < 32 + 0 weeks (p < 0.01). PROM was registered in 22.3% vs. 32.1% (p < 0.001) respectively. Self-measurement of vaginal pH at close intervals, as recommended by Saling, leads to the early

  3. Gene expression of manganese superoxide dismutase in human glioma cells

    Directory of Open Access Journals (Sweden)

    Novi S. Hardiany

    2010-02-01

    Full Text Available Aim This study analyze the MnSOD gene expression as endogenous antioxidant in human glioma cells compared with leucocyte cells as control.Methods MnSOD gene expression of 20 glioma patients was analyzed by measuring the relative expression of mRNA and enzyme activity of MnSOD in brain and leucocyte cells. The relative expression of mRNA MnSOD was determined by using quantitative Real Time RT-PCR and the enzyme activity of MnSOD using biochemical kit assay (xantine oxidase inhibition. Statistic analysis for mRNA and enzyme activity of MnSOD was performed using Kruskal Wallis test.Results mRNA of MnSOD in glioma cells of 70% sample was 0.015–0.627 lower, 10% was 1.002-1.059 and 20% was 1.409-6.915 higher than in leucocyte cells. Also the specific activity of MnSOD enzyme in glioma cells of 80% sample showed 0,064-0,506 lower and 20% sample was 1.249-2.718 higher than in leucocyte cells.Conclusion MnSOD gene expression in human glioma cells are significantly lower than its expression in leucocytes cells. (Med J Indones 2010; 19:21-5Keywords : MnSOD, glioma, gene expression

  4. Lung function and exercise capacity in young adults born prematurely

    NARCIS (Netherlands)

    Vrijlandt, EJLE; Gerritsen, J; Boezen, HM; Grevink, RG; Duiverman, EJ

    2006-01-01

    Rationale: Limited information is available about the long-term outcome of lung function and exercise capacity in young adults born prematurely. Objective: To determine long-term effects of prematurity on lung function (volumes, diffusing capacity) and exercise capacity in expreterms compared with

  5. Anemia of prematurity : time for a change in transfusion management?

    NARCIS (Netherlands)

    Khodabux, Chantal Muriel

    2013-01-01

    In this thesis we investigated clinical effects of allogeneic red blood cell (RBC) transfusions in premature infants, different transfusion volumes in relation to neonatal outcome in premature infants and the use of autologous cord blood (CB) as an alternative for allogeneic transfusions. Despite

  6. Expression of LDOC1 mRNA in leucocytes of patients with Down's ...

    Indian Academy of Sciences (India)

    can develop premature ageing and some traits of Alzheimer disease at an ... expression in brain and thyroid and low expression in pla- centa, liver, and .... Age (years) Sex. (LDOC1 gene) ... cytes in children with Down syndrome. Immun.

  7. Economic analysis of the costs associated with prematurity from a literature review.

    Science.gov (United States)

    Soilly, A L; Lejeune, C; Quantin, C; Bejean, S; Gouyon, J B

    2014-01-01

    To analyse published cost-of-illness studies that had assessed the cost of prematurity according to gestational age at birth. A review of the literature was carried out in March 2011 using the following databases: Medline, ScienceDirect, The Cochrane Library, Econlit and Business Source Premier, and a French Public-Health database. Key-word sequences related to 'prematurity' and 'costs' were considered. Studies that assessed costs according to the gestational age (GA) at the premature birth (prematurity (extreme, early, moderate and late). Results showed that whatever the follow-up period, costs correlated inversely with GA. They also showed considerable variability in costs within the same GA group. Differences between studies could be explained by the choices made, concerning i/the study populations, ii/contextual information, iii/and various economic criteria. Despite these variations, a global trend of costs was estimated in the short-term period using mean costs from four American studies that presented similar methodologies. Costs stand at over US$ 100,000 for extreme prematurity, between US$ 40,000 and US$ 100,000 for early prematurity, between US$ 10,000 and US$ 30,000 for moderate prematurity and below US$ 4500 for late prematurity. This review underlined not only the clear inverse relationship between costs and GA at birth, but also the difficulty to transfer the results to the French context. It suggests that studies specific to the French health system need to be carried out. Copyright © 2013 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

  8. Maternal Iron Deficiency Anemia as a Risk Factor for the Development of Retinopathy of Prematurity.

    Science.gov (United States)

    Dai, Alper I; Demiryürek, Seniz; Aksoy, Sefika Nur; Perk, Peren; Saygili, Oguzhan; Güngör, Kivanc

    2015-08-01

    Retinopathy of prematurity is a proliferative vascular disease affecting premature newborns and occurs during vessel development and maturation. The aim of this study was to evaluate the maternal iron deficiency anemia as possible risk factors associated with the development of retinopathy of prematurity among premature or very low birth weight infants. In this study, mothers of 254 infants with retinopathy of prematurity were analyzed retrospectively, and their laboratory results of medical records during pregnancy were reviewed for possible iron deficiency anemia. In a cohort of 254 mothers of premature infants with retinopathy of prematurity, 187 (73.6%) had iron deficiency, while the remaining 67 (26.4%) mothers had no deficiency. Babies born to mothers with iron deficiency anemia with markedly decreased hemoglobin, hematocrit, mean corpuscular volume, serum iron, and ferritin levels were more likely to develop retinopathy of prematurity. Our results are the first to suggest that maternal iron deficiency is a risk factor for the development of retinopathy of prematurity. Our data suggest that maternal iron supplementation therapy during pregnancy might lower the risk of retinopathy of prematurity. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Development of a high yielding E. coli periplasmic expression system for the production of humanized Fab' fragments.

    Science.gov (United States)

    Ellis, Mark; Patel, Pareshkumar; Edon, Marjory; Ramage, Walter; Dickinson, Robert; Humphreys, David P

    2017-01-01

    Humanized Fab' fragments may be produced in the periplasm of Escherichia coli but can be subject to degradation by host cell proteases. In order to increase Fab' yield and reduce proteolysis we developed periplasmic protease deficient strains of E. coli. These strains lacked the protease activity of Tsp, protease III and DegP. High cell density fermentations indicated Tsp deficient strains increased productivity two fold but this increase was accompanied by premature cell lysis soon after the induction of Fab' expression. To overcome the reduction in cell viability we introduced suppressor mutations into the spr gene. The mutations partially restored the wild type phenotype of the cells. Furthermore, we coexpressed a range of periplasmic chaperone proteins with the Fab', DsbC had the most significant impact, increasing humanized Fab' production during high cell density fermentation. When DsbC coexpression was combined with a Tsp deficient spr strain we observed an increase in yield and essentially restored "wild type" cell viability. We achieved a final periplasmic yield of over 2.4g/L (final cell density OD 600 105), 40 h post Fab' induction with minimal cell lysis.The data suggests that proteolysis, periplasm integrity, protein folding and disulphide bond formation are all potential limiting steps in the production of Fab' fragments in the periplasm of E. coli. In this body of work, we have addressed these limiting steps by utilizing stabilized protease deficient strains and chaperone coexpression. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 33:212-220, 2017. © 2016 American Institute of Chemical Engineers.

  10. Rate of evolution in brain-expressed genes in humans and other primates.

    Directory of Open Access Journals (Sweden)

    Hurng-Yi Wang

    2007-02-01

    Full Text Available Brain-expressed genes are known to evolve slowly in mammals. Nevertheless, since brains of higher primates have evolved rapidly, one might expect acceleration in DNA sequence evolution in their brain-expressed genes. In this study, we carried out full-length cDNA sequencing on the brain transcriptome of an Old World monkey (OWM and then conducted three-way comparisons among (i mouse, OWM, and human, and (ii OWM, chimpanzee, and human. Although brain-expressed genes indeed appear to evolve more rapidly in species with more advanced brains (apes > OWM > mouse, a similar lineage effect is observable for most other genes. The broad inclusion of genes in the reference set to represent the genomic average is therefore critical to this type of analysis. Calibrated against the genomic average, the rate of evolution among brain-expressed genes is probably lower (or at most equal in humans than in chimpanzee and OWM. Interestingly, the trend of slow evolution in coding sequence is no less pronounced among brain-specific genes, vis-à-vis brain-expressed genes in general. The human brain may thus differ from those of our close relatives in two opposite directions: (i faster evolution in gene expression, and (ii a likely slowdown in the evolution of protein sequences. Possible explanations and hypotheses are discussed.

  11. Differentially expressed wound healing-related microRNAs in the human diabetic cornea.

    Science.gov (United States)

    Funari, Vincent A; Winkler, Michael; Brown, Jordan; Dimitrijevich, Slobodan D; Ljubimov, Alexander V; Saghizadeh, Mehrnoosh

    2013-01-01

    MicroRNAs are powerful gene expression regulators, but their corneal repertoire and potential changes in corneal diseases remain unknown. Our purpose was to identify miRNAs altered in the human diabetic cornea by microarray analysis, and to examine their effects on wound healing in cultured telomerase-immortalized human corneal epithelial cells (HCEC) in vitro. Total RNA was extracted from age-matched human autopsy normal (n=6) and diabetic (n=6) central corneas, Flash Tag end-labeled, and hybridized to Affymetrix® GeneChip® miRNA Arrays. Select miRNAs associated with diabetic cornea were validated by quantitative RT-PCR (Q-PCR) and by in situ hybridization (ISH) in independent samples. HCEC were transfected with human pre-miR™miRNA precursors (h-miR) or their inhibitors (antagomirs) using Lipofectamine 2000. Confluent transfected cultures were scratch-wounded with P200 pipette tip. Wound closure was monitored by digital photography. Expression of signaling proteins was detected by immunostaining and Western blot. Using microarrays, 29 miRNAs were identified as differentially expressed in diabetic samples. Two miRNA candidates showing the highest fold increased in expression in the diabetic cornea were confirmed by Q-PCR and further characterized. HCEC transfection with h-miR-146a or h-miR-424 significantly retarded wound closure, but their respective antagomirs significantly enhanced wound healing vs. controls. Cells treated with h-miR-146a or h-miR-424 had decreased p-p38 and p-EGFR staining, but these increased over control levels close to the wound edge upon antagomir treatment. In conclusion, several miRNAs with increased expression in human diabetic central corneas were found. Two such miRNAs inhibited cultured corneal epithelial cell wound healing. Dysregulation of miRNA expression in human diabetic cornea may be an important mediator of abnormal wound healing.

  12. Differentially expressed wound healing-related microRNAs in the human diabetic cornea.

    Directory of Open Access Journals (Sweden)

    Vincent A Funari

    Full Text Available MicroRNAs are powerful gene expression regulators, but their corneal repertoire and potential changes in corneal diseases remain unknown. Our purpose was to identify miRNAs altered in the human diabetic cornea by microarray analysis, and to examine their effects on wound healing in cultured telomerase-immortalized human corneal epithelial cells (HCEC in vitro. Total RNA was extracted from age-matched human autopsy normal (n=6 and diabetic (n=6 central corneas, Flash Tag end-labeled, and hybridized to Affymetrix® GeneChip® miRNA Arrays. Select miRNAs associated with diabetic cornea were validated by quantitative RT-PCR (Q-PCR and by in situ hybridization (ISH in independent samples. HCEC were transfected with human pre-miR™miRNA precursors (h-miR or their inhibitors (antagomirs using Lipofectamine 2000. Confluent transfected cultures were scratch-wounded with P200 pipette tip. Wound closure was monitored by digital photography. Expression of signaling proteins was detected by immunostaining and Western blot. Using microarrays, 29 miRNAs were identified as differentially expressed in diabetic samples. Two miRNA candidates showing the highest fold increased in expression in the diabetic cornea were confirmed by Q-PCR and further characterized. HCEC transfection with h-miR-146a or h-miR-424 significantly retarded wound closure, but their respective antagomirs significantly enhanced wound healing vs. controls. Cells treated with h-miR-146a or h-miR-424 had decreased p-p38 and p-EGFR staining, but these increased over control levels close to the wound edge upon antagomir treatment. In conclusion, several miRNAs with increased expression in human diabetic central corneas were found. Two such miRNAs inhibited cultured corneal epithelial cell wound healing. Dysregulation of miRNA expression in human diabetic cornea may be an important mediator of abnormal wound healing.

  13. Dynamic gene expression response to altered gravity in human T cells.

    Science.gov (United States)

    Thiel, Cora S; Hauschild, Swantje; Huge, Andreas; Tauber, Svantje; Lauber, Beatrice A; Polzer, Jennifer; Paulsen, Katrin; Lier, Hartwin; Engelmann, Frank; Schmitz, Burkhard; Schütte, Andreas; Layer, Liliana E; Ullrich, Oliver

    2017-07-12

    We investigated the dynamics of immediate and initial gene expression response to different gravitational environments in human Jurkat T lymphocytic cells and compared expression profiles to identify potential gravity-regulated genes and adaptation processes. We used the Affymetrix GeneChip® Human Transcriptome Array 2.0 containing 44,699 protein coding genes and 22,829 non-protein coding genes and performed the experiments during a parabolic flight and a suborbital ballistic rocket mission to cross-validate gravity-regulated gene expression through independent research platforms and different sets of control experiments to exclude other factors than alteration of gravity. We found that gene expression in human T cells rapidly responded to altered gravity in the time frame of 20 s and 5 min. The initial response to microgravity involved mostly regulatory RNAs. We identified three gravity-regulated genes which could be cross-validated in both completely independent experiment missions: ATP6V1A/D, a vacuolar H + -ATPase (V-ATPase) responsible for acidification during bone resorption, IGHD3-3/IGHD3-10, diversity genes of the immunoglobulin heavy-chain locus participating in V(D)J recombination, and LINC00837, a long intergenic non-protein coding RNA. Due to the extensive and rapid alteration of gene expression associated with regulatory RNAs, we conclude that human cells are equipped with a robust and efficient adaptation potential when challenged with altered gravitational environments.

  14. D2-40/podoplanin expression in the human placenta

    Science.gov (United States)

    Wang, Yuping; Sun, Jingxia; Gu, Yang; Zhao, Shuang; Groome, Lynn J.; Alexander, J. Steven

    2011-01-01

    Placental tissue expresses many lymphatic markers. The current study was undertaken to examine if D2-40/podoplanin, a lymphatic endothelial marker, was expressed in the human placentas, and how it is altered developmentally and pathologically. We studied D2-40/podoplanin and VEGFR-3 expressions in placentas from normotensive pregnancies at different gestational ages and in placentas from women with clinically defined preeclampsia. D2-40 expression in systemic lymphatic vessel endothelium served as a positive control. Protein expression for D2-40, VEGFR-3, and β-actin were determined by Western blot in placentas from normotensive (n=6) and preeclamptic (n=5) pregnancies. Our results show that D2-40/podoplanin was strongly expressed in the placenta, mainly as a network plexus pattern in the villous stroma throughout gestation. CD31 was limited to villous core fetal vessel endothelium and VEGFR-3 was found in both villous core fetal vessel endothelium and trophoblasts. D2-40/podoplanin expression was significantly decreased, and VEGFR-3 significantly increased in preeclamptic placental tissues compared to normotensive placental controls. Placental villous stroma is a reticular-like structure, and the localization of D2-40 to the stroma suggests that a lymphatic-like conductive network may exist in the human placenta. D2-40/podoplanin is an O-linked sialoglycoprotein. Although little is known regarding biological functions of sialylated glycoproteins within the placenta, placental D2-40/podoplanin may support fetal vessel angiogenesis during placenta development and reduced D2-40/podoplanin expression in preeclamptic placenta may contribute to altered interstitial fluid homeostasis and impaired angiogenesis in this pregnancy disorder. PMID:21095001

  15. Effects of prematurity on language acquisition and auditory maturation: a systematic review.

    Science.gov (United States)

    Rechia, Inaê Costa; Oliveira, Luciéle Dias; Crestani, Anelise Henrich; Biaggio, Eliara Pinto Vieira; Souza, Ana Paula Ramos de

    2016-01-01

    To verify which damages prematurity causes to hearing and language. We used the decriptors language/linguagem, hearing/audição, prematurity/prematuridade in databases LILACS, MEDLINE, Cochrane Library and Scielo. randomized controlled trials, non-randomized intervention studies and descriptive studies (cross-sectional, cohort, case-control projects). The articles were assessed independently by two authors according to the selection criteria. Twenty-six studies were selected, of which seven were published in Brazil and 19 in international literature. Nineteen studies comparing full-term and preterm infants. Two of the studies made comparisons between premature infants small for gestational age and appropriate for gestational age. In four studies, the sample consisted of children with extreme prematurity, while other studies have been conducted in children with severe and moderate prematurity. To assess hearing, these studies used otoacoustic emissions, brainstem evoked potentials, tympanometry, auditory steady-state response and visual reinforcement audiometry. For language assessment, most of the articles used the Bayley Scale of Infant and Toddler Development. Most studies reviewed observed that prematurity is directly or indirectly related to the acquisition of auditory and language abilities early in life. Thus, it could be seen that prematurity, as well as aspects related to it (gestational age, low weight at birth and complications at birth), affect maturation of the central auditory pathway and may cause negative effects on language acquisition.

  16. Signaling pathways in PACAP regulation of VIP gene expression in human neuroblastoma cells

    DEFF Research Database (Denmark)

    Falktoft, B.; Georg, B.; Fahrenkrug, J.

    2009-01-01

    Ganglia expressing the neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) innervate vasoactive intestinal peptide (VIP) containing neurons suggesting a role of PACAP in regulating VIP expression. Human NB-1 neuroblastoma cells were applied to study PACAP regulated VIP gene...... in PACAP regulation of the FOS and VIP gene expressions suggest for the first time a role of FOS in PACAP-induced VIP gene expression in human NB-1 neuroblastoma cells. (C) 2009 Elsevier Ltd. All rights reserved Udgivelsesdato: 2009/10...

  17. The circadian variation of premature atrial contractions

    DEFF Research Database (Denmark)

    Larsen, Bjørn Strøier; Kumarathurai, Preman; Nielsen, Olav W

    2016-01-01

    AIMS: The aim of the study was to assess a possible circadian variation of premature atrial contractions (PACs) in a community-based population and to determine if the daily variation could be used to assess a more vulnerable period of PACs in predicting later incidence of atrial fibrillation (AF...... variation in heart rate. After adjusting for relevant risk factors, the risk of AF was equal in all time intervals throughout the day. CONCLUSION: Premature atrial contractions showed a circadian variation in subjects with frequent PACs. No specific time interval of the day was more predictive of AF than...

  18. PREMATURE BIRTH AS A MEDICAL AND SOCIAL HEALTHCARE PROBLEM. PART 2

    Directory of Open Access Journals (Sweden)

    E. S. Sakharova

    2017-01-01

    Full Text Available Morbidity and mortality, like a frequency of long-term unfavourable psychomotor developmental outcomes is in inverse relationship with gestational age and birth weight. Now scientists give attention to the risk factors — the infection, preeclampsia, smoking, etc., to look for prevention of premature birth. The outcome of premature baby depends on the birth weight; the methodof labor and the hospital technical support also have an influence. The frequency of neurological impairments — infantile cerebral palsy, visual and hearing disorders, and probability of severe bronchopulmonary dysplasia are also in inverse relationship with gestational age and birth weight. Last decade there are many scientists give attention to the cognitive deficit and behavior disorders in adolescents, born premature. Premature infants with extremely low birth weight have developmental disorders at 8-13%. Not all of cognitive and behavioral problems have symptoms in the first years of life, but have delayed unfavourable effects. The severity of cognitive deficit not always corresponds with structural impairments of brain, detected in functional studies of premature baby in the first year of life.  

  19. Maternal experiences with premature children in a neonatal intensive care unit

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    Raphael Colares de Sá

    2012-06-01

    Full Text Available Objective: Understand the maternal experience with premature children in neonatal intensive care unit. Methods: This is a qualitative and descriptive study. A questionnaire was used with semi-structured interview type, analyzed by the technique of content analysis and discussed, using the theoretical framework. The sample consisted of 11 mothers who accompanied their babies every day in the Neonatal Intensive Care Unit. Results: After discourse analysis emerged the following categories: experiencing maternal feelings in relation to the baby at risk; the meaning of the neonatal unit for mothers of premature infants, maternal perceptions about prematurity and experiencing the formation of the maternal-filial bond. Conclusions:The mother of premature experiences difficult times in the face of risk and instability of the baby, causing ambivalent feelings in relation to prematurity. Nevertheless, it was found thatfeelings of happiness, love and desire to see your baby being discharged form hospital and live with his family, were significant in relation to feelings of sadness and fear of losing her child.

  20. Abnormal cortical development after premature birth shown by altered allometric scaling of brain growth.

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    Olga Kapellou

    2006-08-01

    Full Text Available We postulated that during ontogenesis cortical surface area and cerebral volume are related by a scaling law whose exponent gives a quantitative measure of cortical development. We used this approach to investigate the hypothesis that premature termination of the intrauterine environment by preterm birth reduces cortical development in a dose-dependent manner, providing a neural substrate for functional impairment.We analyzed 274 magnetic resonance images that recorded brain growth from 23 to 48 wk of gestation in 113 extremely preterm infants born at 22 to 29 wk of gestation, 63 of whom underwent neurodevelopmental assessment at a median age of 2 y. Cortical surface area was related to cerebral volume by a scaling law with an exponent of 1.29 (95% confidence interval, 1.25-1.33, which was proportional to later neurodevelopmental impairment. Increasing prematurity and male gender were associated with a lower scaling exponent (p < 0.0001 independent of intrauterine or postnatal somatic growth.Human brain growth obeys an allometric scaling relation that is disrupted by preterm birth in a dose-dependent, sexually dimorphic fashion that directly parallels the incidence of neurodevelopmental impairments in preterm infants. This result focuses attention on brain growth and cortical development during the weeks following preterm delivery as a neural substrate for neurodevelopmental impairment after premature delivery.

  1. Imprinted Expression of SNRPN in Human Preimplantation Embryos

    OpenAIRE

    Huntriss, John; Daniels, Robert; Bolton, Virginia; Monk, Marilyn

    1998-01-01

    Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are two clinically distinct neurogenetic disorders arising from a loss of expression of imprinted genes within the human chromosome region 15q11-q13. Recent evidence suggests that the SNRPN gene, which is defective in PWS, plays a central role in the imprinting-center regulation of the PWS/AS region. To increase our understanding of the regulation of expression of this imprinted gene, we have developed single-cell-sensitive procedures for...

  2. Sex-Dependent Gene Expression in Human Pluripotent Stem Cells

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    Daniel Ronen

    2014-08-01

    Full Text Available Males and females have a variety of sexually dimorphic traits, most of which result from hormonal differences. However, differences between male and female embryos initiate very early in development, before hormonal influence begins, suggesting the presence of genetically driven sexual dimorphisms. By comparing the gene expression profiles of male and X-inactivated female human pluripotent stem cells, we detected Y-chromosome-driven effects. We discovered that the sex-determining gene SRY is expressed in human male pluripotent stem cells and is induced by reprogramming. In addition, we detected more than 200 differentially expressed autosomal genes in male and female embryonic stem cells. Some of these genes are involved in steroid metabolism pathways and lead to sex-dependent differentiation in response to the estrogen precursor estrone. Thus, we propose that the presence of the Y chromosome and specifically SRY may drive sex-specific differences in the growth and differentiation of pluripotent stem cells.

  3. Screening for retinopathy of prematurity and treatment outcome in a tertiary hospital in Hong Kong.

    Science.gov (United States)

    Iu, L Pl; Lai, C Hy; Fan, M Cy; Wong, I Yh; Lai, J Sm

    2017-02-01

    Studies on the prevalence and severity of retinopathy of prematurity in the local population are scarce. This study aimed to evaluate the prevalence, screening, and treatment outcome of retinopathy of prematurity in a tertiary hospital in Hong Kong. This cross-sectional study with internal comparison was conducted at Queen Mary Hospital, Hong Kong. The study evaluated 89 premature infants who were born at the hospital and were screened for retinopathy of prematurity, in accordance with the 2008 British Guidelines, between January 2013 and December 2013. The prevalences of retinopathy of prematurity and severe retinopathy requiring treatment were studied. The mean (± standard deviation) gestational age at birth was 30 +2 weeks ± 16.5 days (range, 24 +1 to 35 +5 weeks). The mean birth weight was 1285 g ± 328 g (range, 580 g to 2030 g). A total of 15 (16.9%) infants developed retinopathy of prematurity and three (3.4%) required treatment. In a subgroup analysis of extremely-low-birth-weight infants of prematurity and 17.6% required treatment. Multivariate logistic regression analysis suggested low birth weight and patent ductus arteriosus were significantly associated with development of retinopathy of prematurity (Pprematurity, all regressed successfully after one laser treatment. Retinopathy of prematurity is a significant problem among premature infants in Hong Kong, especially those with extremely low birth weight. Our screening service for retinopathy of prematurity was satisfactory and treatment results were good. Strict adherence to international screening guidelines and vigilance in infants at risk are key to successful management of retinopathy of prematurity.

  4. Serial Analysis of Gene Expression: Applications in Human Studies

    Directory of Open Access Journals (Sweden)

    Tuteja Renu

    2004-01-01

    Full Text Available Serial analysis of gene expression (SAGE is a powerful tool, which provides quantitative and comprehensive expression profile of genes in a given cell population. It works by isolating short fragments of genetic information from the expressed genes that are present in the cell being studied. These short sequences, called SAGE tags, are linked together for efficient sequencing. The frequency of each SAGE tag in the cloned multimers directly reflects the transcript abundance. Therefore, SAGE results in an accurate picture of gene expression at both the qualitative and the quantitative levels. It does not require a hybridization probe for each transcript and allows new genes to be discovered. This technique has been applied widely in human studies and various SAGE tags/SAGE libraries have been generated from different cells/tissues such as dendritic cells, lung fibroblast cells, oocytes, thyroid tissue, B-cell lymphoma, cultured keratinocytes, muscles, brain tissues, sciatic nerve, cultured Schwann cells, cord blood-derived mast cells, retina, macula, retinal pigment epithelial cells, skin cells, and so forth. In this review we present the updated information on the applications of SAGE technology mainly to human studies.

  5. Characterisation of the expression of NMDA receptors in human astrocytes.

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    Ming-Chak Lee

    Full Text Available Astrocytes have long been perceived only as structural and supporting cells within the central nervous system (CNS. However, the discovery that these glial cells may potentially express receptors capable of responding to endogenous neurotransmitters has resulted in the need to reassess astrocytic physiology. The aim of the current study was to characterise the expression of NMDA receptors (NMDARs in primary human astrocytes, and investigate their response to physiological and excitotoxic concentrations of the known endogenous NMDAR agonists, glutamate and quinolinic acid (QUIN. Primary cultures of human astrocytes were used to examine expression of these receptors at the mRNA level using RT-PCR and qPCR, and at the protein level using immunocytochemistry. The functionality role of the receptors was assessed using intracellular calcium influx experiments and measuring extracellular lactate dehydrogenase (LDH activity in primary cultures of human astrocytes treated with glutamate and QUIN. We found that all seven currently known NMDAR subunits (NR1, NR2A, NR2B, NR2C, NR2D, NR3A and NR3B are expressed in astrocytes, but at different levels. Calcium influx studies revealed that both glutamate and QUIN could activate astrocytic NMDARs, which stimulates Ca2+ influx into the cell and can result in dysfunction and death of astrocytes. Our data also show that the NMDAR ion channel blockers, MK801, and memantine can attenuate glutamate and QUIN mediated cell excitotoxicity. This suggests that the mechanism of glutamate and QUIN gliotoxicity is at least partially mediated by excessive stimulation of NMDARs. The present study is the first to provide definitive evidence for the existence of functional NMDAR expression in human primary astrocytes. This discovery has significant implications for redefining the cellular interaction between glia and neurons in both physiological processes and pathological conditions.

  6. The consequence of phototherapy exposure on oxidative stress status of expressed human milk.

    Science.gov (United States)

    Unal, Sezin; Demirel, Nihal; Yaprak Sul, Deniz; Ulubas Isik, Dilek; Erol, Sara; Neselioglu, Salim; Erel, Ozcan; Bas, Ahmet Yagmur

    2017-09-04

    There exists evidence that phototherapy can disturb the oxidant/antioxidant balance in favor of oxidants. If phototherapy is continued during tube feeding in preterms, expressed human milk is subjected to phototherapy lights for about 20 min per feeding. We aimed to investigate the effects of phototherapy lights on oxidative/antioxidative status of expressed human milk. Milk samples of 50 healthy mothers were grouped as control and phototherapy and exposed to 20 min of day-light and phototherapy light, respectively. Total antioxidant capacity (mmol-Trolox equiv/L) and total oxidant status (mmol-H 2 O 2 /L) in expressed human milk samples were measured. Levels of antioxidant capacity of the expressed human milks in the phototherapy group were lower than those of the control group [mmol-Trolox equiv/L; median (interquartile-range): 1.30 (0.89-1.65) and 1.77 (1.51-2.06), p: antioxidant capacity of expressed human milk without any alteration in oxidative status. We think that this observation is important for the care of very low birth weighted infants who have limited antioxidant capacity and are vulnerable to oxidative stress. It may be advisable either to turn off the phototherapy or cover the tube and syringe to preserve antioxidant capacity of human milk during simultaneous tube feeding and phototherapy treatment.

  7. Human BCAS3 expression in embryonic stem cells and vascular precursors suggests a role in human embryogenesis and tumor angiogenesis.

    Directory of Open Access Journals (Sweden)

    Kavitha Siva

    Full Text Available Cancer is often associated with multiple and progressive genetic alterations in genes that are important for normal development. BCAS3 (Breast Cancer Amplified Sequence 3 is a gene of unknown function on human chromosome 17q23, a region associated with breakpoints of several neoplasms. The normal expression pattern of BCAS3 has not been studied, though it is implicated in breast cancer progression. Rudhira, a murine WD40 domain protein that is 98% identical to BCAS3 is expressed in embryonic stem (ES cells, erythropoiesis and angiogenesis. This suggests that BCAS3 expression also may not be restricted to mammary tissue and may have important roles in other normal as well as malignant tissues. We show that BCAS3 is also expressed in human ES cells and during their differentiation into blood vascular precursors. We find that BCAS3 is aberrantly expressed in malignant human brain lesions. In glioblastoma, hemangiopericytoma and brain abscess we note high levels of BCAS3 expression in tumor cells and some blood vessels. BCAS3 may be associated with multiple cancerous and rapidly proliferating cells and hence the expression, function and regulation of this gene merits further investigation. We suggest that BCAS3 is mis-expressed in brain tumors and could serve as a human ES cell and tumor marker.

  8. Human microglia and astrocytes express cGAS-STING viral sensing components.

    Science.gov (United States)

    Jeffries, Austin M; Marriott, Ian

    2017-09-29

    While microglia and astrocytes are known to produce key inflammatory and anti-viral mediators following infection with replicative DNA viruses, the mechanisms by which these cell types perceive such threats are poorly understood. Recently, cyclic GMP-AMP synthase (cGAS) has been identified as an important cytosolic sensor for DNA viruses and retroviruses in peripheral leukocytes. Here we confirm the ability of human microglial and astrocytic cell lines and primary human glia to respond to foreign intracellular double stranded DNA. Importantly, we provide the first demonstration that human microglia and astrocytes show robust levels of cGAS protein expression at rest and following activation. Furthermore, we show these cell types also constitutively express the critical downstream cGAS adaptor protein, stimulator of interferon genes (STING). The present finding that human glia express the principle components of the cGAS-STING pathway provides a foundation for future studies to investigate the relative importance of these molecules in clinically relevant viral CNS infections. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Expression of human α-fetoprotein in yeast

    International Nuclear Information System (INIS)

    Yamamoto, Ritsu; Sakamoto, Takashi; Nishi, Shinzo; Sakai, Masaharu; Morinaga, Tomonori; Tamaoki, Taiki

    1990-01-01

    Human α-fetoprotein (AFP) was expressed in Saccharomyces cerevisiae, with a plasmid containing the cDNA sequence for human AFP fused with the rat AFP signal peptide. The recombinant AFP was purified from the yeast lysate by DEAE-cellulose and immunoaffinity chromatography. The amino acid composition and the molecular weight of the recombinant AFP were similar to those of hepatoma AFP. N-terminal amino acids sequence analysis indicated that the signal peptide had been processed. The recombinant and hepatoma AFP reacted identically in Ouchterlony immunodiffusion and radioimmunoassay tests. These observations indicated that the yeast recombinant protein had the properties of native AFP

  10. Mitochondrial dysfunction in alveolar and white matter developmental failure in premature infants.

    Science.gov (United States)

    Ten, Vadim S

    2017-02-01

    At birth, some organs in premature infants are not developed enough to meet challenges of the extra-uterine life. Although growth and maturation continues after premature birth, postnatal organ development may become sluggish or even arrested, leading to organ dysfunction. There is no clear mechanistic concept of this postnatal organ developmental failure in premature neonates. This review introduces a concept-forming hypothesis: Mitochondrial bioenergetic dysfunction is a fundamental mechanism of organs maturation failure in premature infants. Data collected in support of this hypothesis are relevant to two major diseases of prematurity: white matter injury and broncho-pulmonary dysplasia. In these diseases, totally different clinical manifestations are defined by the same biological process, developmental failure of the main functional units-alveoli in the lungs and axonal myelination in the brain. Although molecular pathways regulating alveolar and white matter maturation differ, proper bioenergetic support of growth and maturation remains critical biological requirement for any actively developing organ. Literature analysis suggests that successful postnatal pulmonary and white matter development highly depends on mitochondrial function which can be inhibited by sublethal postnatal stress. In premature infants, sublethal stress results mostly in organ maturation failure without excessive cellular demise.

  11. Gently does it: Humans outperform a software classifier in recognizing subtle, nonstereotypical facial expressions.

    Science.gov (United States)

    Yitzhak, Neta; Giladi, Nir; Gurevich, Tanya; Messinger, Daniel S; Prince, Emily B; Martin, Katherine; Aviezer, Hillel

    2017-12-01

    According to dominant theories of affect, humans innately and universally express a set of emotions using specific configurations of prototypical facial activity. Accordingly, thousands of studies have tested emotion recognition using sets of highly intense and stereotypical facial expressions, yet their incidence in real life is virtually unknown. In fact, a commonplace experience is that emotions are expressed in subtle and nonprototypical forms. Such facial expressions are at the focus of the current study. In Experiment 1, we present the development and validation of a novel stimulus set consisting of dynamic and subtle emotional facial displays conveyed without constraining expressers to using prototypical configurations. Although these subtle expressions were more challenging to recognize than prototypical dynamic expressions, they were still well recognized by human raters, and perhaps most importantly, they were rated as more ecological and naturalistic than the prototypical expressions. In Experiment 2, we examined the characteristics of subtle versus prototypical expressions by subjecting them to a software classifier, which used prototypical basic emotion criteria. Although the software was highly successful at classifying prototypical expressions, it performed very poorly at classifying the subtle expressions. Further validation was obtained from human expert face coders: Subtle stimuli did not contain many of the key facial movements present in prototypical expressions. Together, these findings suggest that emotions may be successfully conveyed to human viewers using subtle nonprototypical expressions. Although classic prototypical facial expressions are well recognized, they appear less naturalistic and may not capture the richness of everyday emotional communication. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  12. Expression analysis of asthma candidate genes during human and murine lung development.

    Science.gov (United States)

    Melén, Erik; Kho, Alvin T; Sharma, Sunita; Gaedigk, Roger; Leeder, J Steven; Mariani, Thomas J; Carey, Vincent J; Weiss, Scott T; Tantisira, Kelan G

    2011-06-23

    Little is known about the role of most asthma susceptibility genes during human lung development. Genetic determinants for normal lung development are not only important early in life, but also for later lung function. To investigate the role of expression patterns of well-defined asthma susceptibility genes during human and murine lung development. We hypothesized that genes influencing normal airways development would be over-represented by genes associated with asthma. Asthma genes were first identified via comprehensive search of the current literature. Next, we analyzed their expression patterns in the developing human lung during the pseudoglandular (gestational age, 7-16 weeks) and canalicular (17-26 weeks) stages of development, and in the complete developing lung time series of 3 mouse strains: A/J, SW, C57BL6. In total, 96 genes with association to asthma in at least two human populations were identified in the literature. Overall, there was no significant over-representation of the asthma genes among genes differentially expressed during lung development, although trends were seen in the human (Odds ratio, OR 1.22, confidence interval, CI 0.90-1.62) and C57BL6 mouse (OR 1.41, CI 0.92-2.11) data. However, differential expression of some asthma genes was consistent in both developing human and murine lung, e.g. NOD1, EDN1, CCL5, RORA and HLA-G. Among the asthma genes identified in genome wide association studies, ROBO1, RORA, HLA-DQB1, IL2RB and PDE10A were differentially expressed during human lung development. Our data provide insight about the role of asthma susceptibility genes during lung development and suggest common mechanisms underlying lung morphogenesis and pathogenesis of respiratory diseases.

  13. Expression and characterization of recombinant human serum ...

    African Journals Online (AJOL)

    C-peptide (CP), connecting the A and B chains in proinsulin, has been considered to possess physiological effects in diabetes. In order to prolong the half-life of CP in vivo, a long acting CP analog [human serum albumin (HSA-CP)] was obtained by direct gene fusion of a single-chain CP to HSA and expressed in host ...

  14. Level of anxiety in parents of high-risk premature twins.

    Science.gov (United States)

    Zanardo, V; Freato, F; Cereda, C

    1998-01-01

    We attempted to define parental anxiety in a population of parents of high-risk premature twins (mean birth weight 1,493 +/- 227 kg; mean gestational age 33 +/- 3.5 weeks), admitted to III level NICU. We specifically examined the following factors; gestational age of the twins, whether or not the twins had ventilatory support, pulmonary sequelae, major malformations or intra-ventricular hemorrhage, parental gender and highest level of education obtained by the parent. In the immediate pre-discharge period and a month later, a questionnaire (State-Trait Anxiety Inventory) was given to all parents of premature twins presenting for the discharge. The parents of 30 twins entered the study twice, at the discharge of their first twin (mean postnatal age 40 +/- 32 days), and one month later. They included 15 mothers and 11 fathers, aged 33 +/- 5.5 and 33 +/- 4.2 years, and at the second evaluation 11 mothers and 10 fathers, respectively. As case-controls we examined parental anxiety of fifteen consecutive singleton high-risk prematures, with equal gestational age, discharged immediately after. Our results indicate that the parents of high-risk twin and singleton prematures present an elevated, lasting state-trait anxiety level. Pre- and post-discharge parental anxiety is more elevated (not significant) in twinning with respect to the prematurity alone. When assessed separately by parental gender, in both these groups an increased (not significant) anxiety was persistently found in the mothers. We recommend that, although neonatologists generally define the discharge of the high-risk premature based upon the acquired stabilization of vital parameters, they pay special attention to the twin group we have identified which is at increased risk for predischarge parental anxiety.

  15. Hierarchical Recognition Scheme for Human Facial Expression Recognition Systems

    Directory of Open Access Journals (Sweden)

    Muhammad Hameed Siddiqi

    2013-12-01

    Full Text Available Over the last decade, human facial expressions recognition (FER has emerged as an important research area. Several factors make FER a challenging research problem. These include varying light conditions in training and test images; need for automatic and accurate face detection before feature extraction; and high similarity among different expressions that makes it difficult to distinguish these expressions with a high accuracy. This work implements a hierarchical linear discriminant analysis-based facial expressions recognition (HL-FER system to tackle these problems. Unlike the previous systems, the HL-FER uses a pre-processing step to eliminate light effects, incorporates a new automatic face detection scheme, employs methods to extract both global and local features, and utilizes a HL-FER to overcome the problem of high similarity among different expressions. Unlike most of the previous works that were evaluated using a single dataset, the performance of the HL-FER is assessed using three publicly available datasets under three different experimental settings: n-fold cross validation based on subjects for each dataset separately; n-fold cross validation rule based on datasets; and, finally, a last set of experiments to assess the effectiveness of each module of the HL-FER separately. Weighted average recognition accuracy of 98.7% across three different datasets, using three classifiers, indicates the success of employing the HL-FER for human FER.

  16. Hierarchical Recognition Scheme for Human Facial Expression Recognition Systems

    Science.gov (United States)

    Siddiqi, Muhammad Hameed; Lee, Sungyoung; Lee, Young-Koo; Khan, Adil Mehmood; Truc, Phan Tran Ho

    2013-01-01

    Over the last decade, human facial expressions recognition (FER) has emerged as an important research area. Several factors make FER a challenging research problem. These include varying light conditions in training and test images; need for automatic and accurate face detection before feature extraction; and high similarity among different expressions that makes it difficult to distinguish these expressions with a high accuracy. This work implements a hierarchical linear discriminant analysis-based facial expressions recognition (HL-FER) system to tackle these problems. Unlike the previous systems, the HL-FER uses a pre-processing step to eliminate light effects, incorporates a new automatic face detection scheme, employs methods to extract both global and local features, and utilizes a HL-FER to overcome the problem of high similarity among different expressions. Unlike most of the previous works that were evaluated using a single dataset, the performance of the HL-FER is assessed using three publicly available datasets under three different experimental settings: n-fold cross validation based on subjects for each dataset separately; n-fold cross validation rule based on datasets; and, finally, a last set of experiments to assess the effectiveness of each module of the HL-FER separately. Weighted average recognition accuracy of 98.7% across three different datasets, using three classifiers, indicates the success of employing the HL-FER for human FER. PMID:24316568

  17. Adult, embryonic and fetal hemoglobin are expressed in human glioblastoma cells.

    Science.gov (United States)

    Emara, Marwan; Turner, A Robert; Allalunis-Turner, Joan

    2014-02-01

    Hemoglobin is a hemoprotein, produced mainly in erythrocytes circulating in the blood. However, non-erythroid hemoglobins have been previously reported in other cell types including human and rodent neurons of embryonic and adult brain, but not astrocytes and oligodendrocytes. Human glioblastoma multiforme (GBM) is the most aggressive tumor among gliomas. However, despite extensive basic and clinical research studies on GBM cells, little is known about glial defence mechanisms that allow these cells to survive and resist various types of treatment. We have shown previously that the newest members of vertebrate globin family, neuroglobin (Ngb) and cytoglobin (Cygb), are expressed in human GBM cells. In this study, we sought to determine whether hemoglobin is also expressed in GBM cells. Conventional RT-PCR, DNA sequencing, western blot analysis, mass spectrometry and fluorescence microscopy were used to investigate globin expression in GBM cell lines (M006x, M059J, M059K, M010b, U87R and U87T) that have unique characteristics in terms of tumor invasion and response to radiotherapy and hypoxia. The data showed that α, β, γ, δ, ζ and ε globins are expressed in all tested GBM cell lines. To our knowledge, we are the first to report expression of fetal, embryonic and adult hemoglobin in GBM cells under normal physiological conditions that may suggest an undefined function of those expressed hemoglobins. Together with our previous reports on globins (Ngb and Cygb) expression in GBM cells, the expression of different hemoglobins may constitute a part of series of active defence mechanisms supporting these cells to resist various types of treatments including chemotherapy and radiotherapy.

  18. Transgenic nude mouse with green fluorescent protein expression-based human glioblastoma multiforme animal model with EGFR expression and invasiveness.

    Science.gov (United States)

    Tan, Guo-Wei; Lan, Fo-Lin; Gao, Jian-Guo; Jiang, Cai-Mou; Zhang, Yi; Huang, Xiao-Hong; Ma, Yue-Hong; Shao, He-Dui; He, Xue-Yang; Chen, Jin-Long; Long, Jian-Wu; Xiao, Hui-Sheng; Guo, Zhi-Tong; Diao, Yi

    2012-08-01

    Previously, we developed an orthotopic xenograft model of human glioblastoma multiforme (GBM) with high EGFR expression and invasiveness in Balb/c nu/nu nude mice. Now we also developed the same orthotopic xenograft model in transgenic nude mice with green fluorescent protein (GFP) expression. The present orthotopic xenografts labeled by phycoerythrin fluorescing red showed high EGFR expression profile, and invasive behavior under a bright green-red dual-color fluorescence background. A striking advantage in the present human GBM model is that the change of tumor growth can be observed visually instead of sacrificing animals in our further antitumor therapy studies.

  19. Human milk donation is an alternative to human milk bank.

    Science.gov (United States)

    Hsu, Ho-Torng; Fong, Tze-Vun; Hassan, Nurulhuda Mat; Wong, Hoi-Ling; Rai, Jasminder Kaur; Khalid, Zorina

    2012-04-01

    Human milk bank is a source of human milk supply in many neonatal intensive care units. However, there are some hospitals without this facility because of financial or religious impediments, such as the Muslim community. We introduced human milk donation as an alternative to human milk banking based on Islamic principles. The suitable donor is a healthy rooming-in mother whose expressed breastmilk is in excess of her baby's demand. The milk is used after 72 hours of freezing at -20°C. The donor must fulfill the criteria for selection of donors and be nonreactive to human immunodeficiency virus and syphilis. Once the recipient's family and the donor state their desire for the human milk donation, a meeting with both parties is made. Unpasteurized frozen-thawed donor's milk will be provided to the recipient after written consents are obtained from both parties. This study was carried out in the Duchess of Kent Hospital (Sandakan, Sabah, Malaysia) between January 2009 and December 2010. A total of 48 babies received donated breastmilk. Forty-two infants were from the special care nursery, and the remaining six were from the pediatric ward. Eighty-eight percent of the donors and 77% of the recipients were Muslims. Sixty percent of the infants who received donated human milk were premature. Two infants died because of the underlying nature of their disease. Human milk donation is an option for hospitals without a human milk bank or in the Muslim community.

  20. Sleep deprivation, pain and prematurity: a review study

    Directory of Open Access Journals (Sweden)

    Kelly Cristina Santos de Carvalho Bonan

    2015-02-01

    Full Text Available The aim was to describe current reports in the scientific literature on sleep in the intensive care environment and sleep deprivation associated with painful experiences in premature infant. A systematic search was conducted for studies on sleep, pain, premature birth and care of the newborn. Web of Knowledge, MEDLINE, LILACS, Cochrane Library, PubMed, EMBASE, Scopus, VHL and SciELO databases were consulted. The association between sleep deprivation and pain generates effects that are observed in the brain and the behavioral and physiological activity of preterm infants. Polysomnography in intensive care units and pain management in neonates allow comparison with the first year of life and term infants. We have found few references and evidence that neonatal care programs can influence sleep development and reduce the negative impact of the environment. This evidence is discussed from the perspective of how hospital intervention can improve the development of premature infants.

  1. Prematurity as a factor of damaged child development

    Directory of Open Access Journals (Sweden)

    Chukhutova G.L.

    2015-03-01

    Full Text Available At present time prematurity is the main reason for disability in children, which can be exemplified by the fact that 2/3 of educatees of children' homes for blind and deaf are preterm children. The most drastic consequences of prematurity is cerebral palsy with spastic diplegia; blindness or poor vision as a result of retina detachment; auditory inefficiency connected with the nerve deafness, decline in general cognitive and speech development; difficulties in coordination and planning serial operations; psycho-emotional impairments like autism. The distinctive features of appearance (failure to thrive, microcephalism with deformation of the shape of the head and behavior (stereotyped movements, lack in initiative purposeful activity make these children recognizable and let us talk about naturally determined set of impairments connected with the main reason — prematurity. The article regards the influence of preterm birth on child's nervous system and it's remote effect on his/her psychic development.

  2. Thigh circumference and risk of heart disease and premature death

    DEFF Research Database (Denmark)

    Heitmann, Berit L; Frederiksen, Peder

    2009-01-01

    of follow-up for total death. RESULTS: A small thigh circumference was associated with an increased risk of cardiovascular and coronary heart diseases and total mortality in both men and women. A threshold effect for thigh circumference was evident, with greatly increased risk of premature death below...... circumference seems to be associated with an increased risk of developing heart disease or premature death. The adverse effects of small thighs might be related to too little muscle mass in the region. The measure of thigh circumference might be a relevant anthropometric measure to help general practitioners...... in early identification of individuals at an increased risk of premature morbidity and mortality....

  3. Gene expression demonstrates an immunological capacity of the human endolymphatic sac

    DEFF Research Database (Denmark)

    Møller, Martin Nue; Kirkeby, Svend; Vikeså, Jonas

    2015-01-01

    OBJECTIVES/HYPOTHESIS: The purpose of the present study is to explore, demonstrate, and describe the expression of genes related to the innate immune system in the human endolymphatic sac. It is hypothesized that the endolymphatic sac has a significant immunological function in the human inner ear...... was obtained. Multiple key elements of both the cellular and humoral innate immune system were expressed, including Toll-like receptors 4 and 7, as well as beta-defensin and lactoferrin. CONCLUSIONS: The present data provides the first direct evidence of an immunological capacity of the human endolymphatic sac...... immunological entity of the inner ear. LEVEL OF EVIDENCE: N/A....

  4. Specific features of physical development in extremely premature infants

    Directory of Open Access Journals (Sweden)

    G. A. Alyamovskaya

    2015-01-01

    Full Text Available The literature review deals with the specilic features of physical development in extremely premature infants weighing less than 1500 g at birth. It describes the regularities of an increment in basic physical development parameters (weight, height, and head circumference within the first year of life. Genetic factors, the specific features of a neonatal period, comorbidity, and different feeding types are shown to affect the increment rates of the physical development parameters. Emphasis is placed on the early initiation of enteral feeding and on the long-term use of fortified foods in low birthweight premature babies for the correction of energy deficiency resulting from preterm birth. The review shows that there is a relationship of the long-term outcomes of physical and psychomotor developments in low birthweight premature babies.

  5. An evaluation of the screening for retinopathy of prematurity in very ...

    African Journals Online (AJOL)

    The principal risk factor was the supply of unmonitored ... of blindness from untreated ROP is likely to increase. It was first ... premature babies at risk of ROP, treating those premature babies .... Stage 5: complete retinal detachment. Extent.

  6. THE PREVENTION OF BLINDNESS AND VISUAL IMPAIRMENT IN CHILDREN WITH RETINOPATHY OF PREMATURITY

    Directory of Open Access Journals (Sweden)

    V. V. Neroev

    2015-01-01

    Full Text Available The system of blindness prevention and visual impairment in children with retinopathy of prematurity is a multidisciplinary medical problem, and includes the prevention of the preterm birth, the correction of terms of caring for premature babies, early detection, monitoring, and treatment of retinopathy of prematurity, as well as the organization of the long clinical supervision. Patients with retinopathy of prematurity need a comprehensive approach to the prevention of the visual impairment in order to ensure high functional outcomes and improve their quality of life. 

  7. [Buffering capacity of the vitreous body in aggressive posterior retinopathy of prematurity].

    Science.gov (United States)

    Amkhanitskaia, L I; Sidorenko, E I; Nikolaeva, G V; Kuznetsova, Iu D

    2014-01-01

    To investigate the role of vitreous body changes in the pathogenesis of aggressive posterior retinopathy of prematurity. The study included 60 children with stage 4-5 retinopathy of prematurity demonstrating either classical or aggressive posterior form of progression. In all cases vitreous samples for laboratory testing were taken during surgery. The study showed that aggressive posterior retinopathy of prematurity is associated with more significant metabolic changes in comparison with classical form of the disease. The degree of biochemical imbalance of the vitreous appeared directly related to the stage of the disease, which was determined by the type and extent of retinal detachment. Volcano-shaped retinal detachment with intensive exudation within the posterior eye segment is considered the most severe variant of aggressive posterior retinopathy of prematurity. Aggressive posterior retinopathy of prematurity is characterized by substantial disturbance of metabolism of the vitreous body, which contributes to exudation and proliferation, thus aggravating the course of the disease and worsening the prognosis.

  8. Quantitative Expression of C-Type Lectin Receptors in Humans and Mice

    Science.gov (United States)

    Lech, Maciej; Susanti, Heni Eka; Römmele, Christoph; Gröbmayr, Regina; Günthner, Roman; Anders, Hans-Joachim

    2012-01-01

    C-type lectin receptors and their adaptor molecules are involved in the recognition of glycosylated self-antigens and pathogens. However, little is known about the species- and organ-specific expression profiles of these molecules. We therefore determined the mRNA expression levels of Dectin-1, MR1, MR2, DC-SIGN, Syk, Card-9, Bcl-10, Malt-1, Src, Dec-205, Galectin-1, Tim-3, Trem-1, and DAP-12 in 11 solid organs of human and mice. Mouse organs revealed lower mRNA levels of most molecules compared to spleen. However, Dec-205 and Galectin-1 in thymus, Src in brain, MR2, Card-9, Bcl-10, Src, and Dec-205 in small intestine, MR2, Bcl-10, Src, Galectin-1 in kidney, and Src and Galectin-1 in muscle were at least 2-fold higher expressed compared to spleen. Human lung, liver and heart expressed higher mRNA levels of most genes compared to spleen. Dectin-1, MR1, Syk and Trem-1 mRNA were strongly up-regulated upon ischemia-reperfusion injury in murine kidney. Tim3, DAP-12, Card-9, DC-SIGN and MR2 were further up-regulated during renal fibrosis. Murine kidney showed higher DAP-12, Syk, Card-9 and Dectin-1 mRNA expression during the progression of lupus nephritis. Thus, the organ-, and species-specific expression of C-type lectin receptors is different between mice and humans which must be considered in the interpretation of related studies. PMID:22949850

  9. Impacts of Neanderthal-Introgressed Sequences on the Landscape of Human Gene Expression.

    Science.gov (United States)

    McCoy, Rajiv C; Wakefield, Jon; Akey, Joshua M

    2017-02-23

    Regulatory variation influencing gene expression is a key contributor to phenotypic diversity, both within and between species. Unfortunately, RNA degrades too rapidly to be recovered from fossil remains, limiting functional genomic insights about our extinct hominin relatives. Many Neanderthal sequences survive in modern humans due to ancient hybridization, providing an opportunity to assess their contributions to transcriptional variation and to test hypotheses about regulatory evolution. We developed a flexible Bayesian statistical approach to quantify allele-specific expression (ASE) in complex RNA-seq datasets. We identified widespread expression differences between Neanderthal and modern human alleles, indicating pervasive cis-regulatory impacts of introgression. Brain regions and testes exhibited significant downregulation of Neanderthal alleles relative to other tissues, consistent with natural selection influencing the tissue-specific regulatory landscape. Our study demonstrates that Neanderthal-inherited sequences are not silent remnants of ancient interbreeding but have measurable impacts on gene expression that contribute to variation in modern human phenotypes. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Effect of White Noise in Relieving Vaccination Pain in Premature Infants.

    Science.gov (United States)

    Kucukoglu, Sibel; Aytekin, Aynur; Celebioglu, Ayda; Celebi, Arzu; Caner, Ibrahim; Maden, Rukiye

    2016-12-01

    The purpose of this study was to evaluate the effect of white noise as a distraction method in relieving procedural pain caused by vaccination for premature infants. This experimental study was performed at a neonatal intensive care unit (NICU) of a university hospital in Turkey between July and September 2013. The study population was composed of 75 premature infants (35 in the study group and 40 in the control group) who met the inclusion criteria. Premature infants in the study group were exposed to white noise using MP3 players placed at the head of the infants' open crib for 1 minute before vaccination. The white noise continued until 1 minute after vaccination. Premature infants in the control group were not exposed to white noise. The Premature Infant Information Form, Intervention Follow-up Form, and Premature Infant Pain Profile (PIPP) were used to collect study data. Descriptive statistics, chi-square test, and independent sample t-tests were used to evaluate the data. The pain level of the control group (PIPP = 14.35 ± 2.59) was significantly higher than the pain level of the study group (PIPP = 8.14 ± 3.14) (p White noise was found to be effective for this sample; however, there is a dire need for extensive research on white noise and its use with this vulnerable population. Copyright © 2016 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

  11. Ventilator flow data predict bronchopulmonary dysplasia in extremely premature neonates

    Directory of Open Access Journals (Sweden)

    Mariann H. Bentsen

    2018-03-01

    Full Text Available Early prediction of bronchopulmonary dysplasia (BPD may facilitate tailored management for neonates at risk. We investigated whether easily accessible flow data from a mechanical ventilator can predict BPD in neonates born extremely premature (EP. In a prospective population-based study of EP-born neonates, flow data were obtained from the ventilator during the first 48 h of life. Data were logged for >10 min and then converted to flow–volume loops using custom-made software. Tidal breathing parameters were calculated and averaged from ≥200 breath cycles, and data were compared between those who later developed moderate/severe and no/mild BPD. Of 33 neonates, 18 developed moderate/severe and 15 no/mild BPD. The groups did not differ in gestational age, surfactant treatment or ventilator settings. The infants who developed moderate/severe BPD had evidence of less airflow obstruction, significantly so for tidal expiratory flow at 50% of tidal expiratory volume (TEF50 expressed as a ratio of peak tidal expiratory flow (PTEF (p=0.007. A compound model estimated by multiple logistic regression incorporating TEF50/PTEF, birthweight z-score and sex predicted moderate/severe BPD with good accuracy (area under the curve 0.893, 95% CI 0.735–0.973. This study suggests that flow data obtained from ventilators during the first hours of life may predict later BPD in premature neonates. Future and larger studies are needed to validate these findings and to determine their clinical usefulness.

  12. Regulation of the human SLC25A20 expression by peroxisome proliferator-activated receptor alpha in human hepatoblastoma cells

    International Nuclear Information System (INIS)

    Tachibana, Keisuke; Takeuchi, Kentaro; Inada, Hirohiko; Yamasaki, Daisuke; Ishimoto, Kenji; Tanaka, Toshiya; Hamakubo, Takao; Sakai, Juro; Kodama, Tatsuhiko; Doi, Takefumi

    2009-01-01

    Solute carrier family 25, member 20 (SLC25A20) is a key molecule that transfers acylcarnitine esters in exchange for free carnitine across the mitochondrial membrane in the mitochondrial β-oxidation. The peroxisome proliferator-activated receptor alpha (PPARα) is a ligand-activated transcription factor that plays an important role in the regulation of β-oxidation. We previously established tetracycline-regulated human cell line that can be induced to express PPARα and found that PPARα induces the SLC25A20 expression. In this study, we analyzed the promoter region of the human slc25a20 gene and showed that PPARα regulates the expression of human SLC25A20 via the peroxisome proliferator responsive element.

  13. Human Cementum Protein 1 induces expression of bone and cementum proteins by human gingival fibroblasts

    International Nuclear Information System (INIS)

    Carmona-Rodriguez, Bruno; Alvarez-Perez, Marco Antonio; Narayanan, A. Sampath; Zeichner-David, Margarita; Reyes-Gasga, Jose; Molina-Guarneros, Juan; Garcia-Hernandez, Ana Lilia; Suarez-Franco, Jose Luis; Chavarria, Ivet Gil; Villarreal-Ramirez, Eduardo; Arzate, Higinio

    2007-01-01

    We recently presented evidence showing that a human cementoblastoma-derived protein, named Cementum Protein 1 (CEMP1) may play a role as a local regulator of cementoblast differentiation and cementum-matrix mineralization. This protein was shown to be expressed by cementoblasts and progenitor cells localized in the periodontal ligament. In this study we demonstrate that transfection of CEMP1 into human gingival fibroblasts (HGF) induces mineralization and expression of bone and cementum-matrix proteins. The transfected HGF cells had higher alkaline phosphatase activity and proliferation rate and they expressed genes for alkaline phosphatase, bone sialoprotein, osteocalcin, osteopontin, the transcription factor Runx2/Cbfa1, and cementum attachment protein (CAP). They also produced biological-type hydroxyapatite. These findings indicate that the CEMP1 might participate in differentiation and mineralization of nonosteogenic cells, and that it might have a potential function in cementum and bone formation

  14. The preterm pig as a model of premature infant gait ataxia

    DEFF Research Database (Denmark)

    Bergström, A.; Ryom, K.; Vanden Hole, C.

    Aims/background Compromised gait, balance and motor coordination (ataxia) as observed in cases of cerebral palsy is a serious complication to premature birth. The cerebellum is a central region with regards to these brain functions and its development shows high sensitivity to premature birth. Our...... group has over many years refined a pig model of premature birth focusing on gut and immune system development. Phenotypically, we have observed distinct motoric problems e.g. falls, tiptoe walking and swaying in preterm pigs relative to term born counterparts, indicating compromised brain function...

  15. Structure and expression of the human and mouse T4 genes

    International Nuclear Information System (INIS)

    Maddon, P.J.; Molineaux, S.M.; Maddon, D.F.; Zimmerman, K.A.; Godfrey, M.; Alt, F.W.; Chess, L.; Axel, R.

    1987-01-01

    The T4 molecule may serve as a T-cell receptor recognizing molecules on the surface of specific target cells and also serves as the receptor for the human immunodeficiency virus. To define the mechanisms of interaction of T4 with the surface of antigen-presenting cells as well as with human immunodeficiency virus, the authors have further analyzed the sequence, structure, and expression of the human and mouse T4 genes. T4 consists of an extracellular segment comprised of a leader sequence followed by four tandem variable-joining (VJ)-like domains, a transmembrane domain, and A cytoplasmic segment. The structural domains of the T4 protein deduced from amino acid sequence are precisely reflected in the intron-exon organization of the gene. Analysis of the expression of the T4 gene indicates that T4 RNA is expressed not only in T lymphocytes, but in B cells, macrophages, and granulocytes. T4 is also expressed in a developmentally regulated manner in specific regions of the brain. It is, therefore, possible that T4 plays a more general role in mediating cell recognition events that are not restricted to the cellular immune response

  16. Expression of a humanized viral 2A-mediated lux operon efficiently generates autonomous bioluminescence in human cells.

    Directory of Open Access Journals (Sweden)

    Tingting Xu

    Full Text Available Expression of autonomous bioluminescence from human cells was previously reported to be impossible, suggesting that all bioluminescent-based mammalian reporter systems must therefore require application of a potentially influential chemical substrate. While this was disproven when the bacterial luciferase (lux cassette was demonstrated to function in a human cell, its expression required multiple genetic constructs, was functional in only a single cell type, and generated a significantly reduced signal compared to substrate-requiring systems. Here we investigate the use of a humanized, viral 2A-linked lux genetic architecture for the efficient introduction of an autobioluminescent phenotype across a variety of human cell lines.The lux cassette was codon optimized and assembled into a synthetic human expression operon using viral 2A elements as linker regions. Human kidney, breast cancer, and colorectal cancer cell lines were both transiently and stably transfected with the humanized operon and the resulting autobioluminescent phenotype was evaluated using common imaging instrumentation. Autobioluminescent cells were screened for cytotoxic effects resulting from lux expression and their utility as bioreporters was evaluated through the demonstration of repeated monitoring of single populations over a prolonged period using both a modified E-SCREEN assay for estrogen detection and a classical cytotoxic compound detection assay for the antibiotic Zeocin. Furthermore, the use of self-directed bioluminescent initiation in response to target detection was assessed to determine its amenability towards deployment as fully autonomous sensors. In all cases, bioluminescent measurements were supported with traditional genetic and transcriptomic evaluations.Our results demonstrate that the viral 2A-linked, humanized lux genetic architecture successfully produced autobioluminescent phenotypes in all cell lines tested without the induction of cytotoxicity

  17. Caffeine is a risk factor for osteopenia of prematurity in preterm infants: a cohort study.

    Science.gov (United States)

    Ali, Ebtihal; Rockman-Greenberg, Cheryl; Moffatt, Michael; Narvey, Michael; Reed, Martin; Jiang, Depeng

    2018-01-22

    Caffeine, the most commonly used medication in Neonatal Intensive Care Units, has calciuric and osteoclastogenic effects. To examine the association between the cumulative dose and duration of therapy of caffeine and osteopenia of prematurity, a retrospective cohort study was conducted including premature infants less than 31 weeks and birth weight less than 1500 g. Osteopenia of prematurity was evaluated using chest X-rays on a biweekly basis over 12 weeks of hospitalization. The cohort included 109 infants. 51% had osteopenia of prematurity and 8% had spontaneous rib fractures. Using the generalized linear mixed model, caffeine dose and duration of caffeine therapy showed a strong association with osteopenia of prematurity. Steroids and vitamin D were also significantly correlated with osteopenia of prematurity while diuretic use did not show a statistically significant effect. The cumulative dose and duration of therapy of caffeine, as well as steroid are associated with osteopenia of prematurity in this cohort. Future studies are needed to confirm these findings and determine the lowest dose of caffeine needed to treat effectively apnea of prematurity.

  18. The influence of premature loss of temporary upper molars on permanent molars.

    Science.gov (United States)

    Cernei, E R; Maxim, Dana Cristiana; Zetu, Irina Nicoleta

    2015-01-01

    Premature loss of primary molars due to dental caries and their complications has been associated with space loss and eruptive difficulties, especially when the loss occurs early. The aim of our study was to determine the impact of premature loss of temporary upper molars upon the longitudinal axis of the first and second upper permanent molar. The study group included 64 patients 6-9 years old with premature loss of primary molars and a control group of 48 patients with intact temporary teeth. It was evaluated the angle between longitudinal axis of first and second upper permanent molars and occlusal plane. The sofware used is Easy Dent 4 Viewer®.The data were analyzed by using the Statistical Package for the Social Sciences (version 20.0; SPSS, Chicago, III). It was observed that premature loss of upper second deciduous molars modifies greater the vertical axis of the permanent molars than the premature loss of first upper primary molar. First upper primary molar loss cause an acceleration eruption of first premolar, which will produce a distal inclintion of the both permanent molars. The use of space maintainers after premature loss of the second upper temporary molar is a last solution in preventing tridimensional lesions in the dental arch and occlusion.

  19. PPARalpha/gamma expression and activity in mouse and human melanocytes and melanoma cells.

    Science.gov (United States)

    Eastham, Linda L; Mills, Caroline N; Niles, Richard M

    2008-06-01

    We examined the expression of PPARs and the effects of PPARalpha and PPARgamma agonists on growth of mouse and human melanocytes and melanoma cells. PPARalpha,beta, and PPARgamma mRNA qualitative expression in melan-a mouse melanocytes, B16 mouse melanoma, human melanocytes, and A375 and SK-mel28 human melanoma cells was determined by RT-PCR, while quantitative PPARalpha mRNA levels were determined by QuantiGene assay. PPARalpha and PPARgamma protein was assessed by Western blotting. The effect of natural and synthetic PPAR ligands on cell growth was determined by either hemocytometer counting or crystal violet assay. PPAR transcriptional activity was determined by a PPRE-reporter gene assay, while knockdown of PPARalpha expression was achieved by transient transfection of siRNA. Both mouse and human melanoma cells produced more PPARalpha and PPARgamma protein compared to melanocytes. PPARalpha mRNA levels were elevated in human melanoma cells, but not in mouse melanoma cells relative to melanocytes. Silencing of PPARalpha in human melanoma cells did not alter cell proliferation or morphology. PPARgamma-selective agonists inhibited the growth of both mouse and human melanoma cells, while PPARalpha-selective agonists had limited effects. Increased expression of PPARalpha in melanoma relative to melanocytes may be a common occurrence, however its biologic significance remains to be determined. PPARgamma agonists may be useful for arresting the growth of some melanomas.

  20. Production of multiple transgenic Yucatan miniature pigs expressing human complement regulatory factors, human CD55, CD59, and H-transferase genes.

    Directory of Open Access Journals (Sweden)

    Young-Hee Jeong

    Full Text Available The present study was conducted to generate transgenic pigs coexpressing human CD55, CD59, and H-transferase (HT using an IRES-mediated polycistronic vector. The study focused on hyperacute rejection (HAR when considering clinical xenotransplantation as an alternative source for human organ transplants. In total, 35 transgenic cloned piglets were produced by somatic cell nuclear transfer (SCNT and were confirmed for genomic integration of the transgenes from umbilical cord samples by PCR analysis. Eighteen swine umbilical vein endothelial cells (SUVEC were isolated from umbilical cord veins freshly obtained from the piglets. We observed a higher expression of transgenes in the transgenic SUVEC (Tg SUVEC compared with the human umbilical vein endothelial cells (HUVEC. Among these genes, HT and hCD59 were expressed at a higher level in the tested Tg organs compared with non-Tg control organs, but there was no difference in hCD55 expression between them. The transgenes in various organs of the Tg clones revealed organ-specific and spatial expression patterns. Using from 0 to 50% human serum solutions, we performed human complement-mediated cytolysis assays. The results showed that, overall, the Tg SUVEC tested had greater survival rates than did the non-Tg SUVEC, and the Tg SUVEC with higher HT expression levels tended to have more down-regulated α-Gal epitope expression, resulting in greater protection against cytotoxicity. By contrast, several Tg SUVEC with low CD55 expression exhibited a decreased resistance response to cytolysis. These results indicated that the levels of HT expression were inversely correlated with the levels of α-Gal epitope expression and that the combined expression of hCD55, hCD59, and HT proteins in SUVECs markedly enhances a protective response to human serum-mediated cytolysis. Taken together, these results suggest that combining a polycistronic vector system with SCNT methods provides a fast and efficient alternative

  1. Retroviral-mediated transfer and expression of human β-globin genes in cultured murine and human erythroid cells

    International Nuclear Information System (INIS)

    Weber-Benarous, A.; Cone, R.D.; London, I.M.; Mulligan, R.C.

    1988-01-01

    The authors cloned human β-globin DNA sequences from a genomic library prepared from DNA isolated from the human leukemia cell line K562 and have used the retroviral vector pZip-NeoSV(X)1 to introduce a 3.0-kilobase segment encompassing the globin gene into mouse erythroleukemia cells. Whereas the endogenous K562 β-globin gene is repressed in K562 cells, when introduced into mouse erythroleukemia cells by retroviral-mediated gene transfer, the β-globin gene from K562 cells was transcribed and induced 5-20-fold after treatment of the cells with dimethyl sulfoxide. The transcripts were correctly initiated, and expression and regulation of the K562 gene were identical to the expression of a normal human β-globin gene transferred into mouse erythroleukemia cells in the same way. They have also introduced the normal human β-globin gene into K562 cells using the same retrovirus vector. SP6 analysis of the RNA isolated from the transduced cells showed that the normal β-globin gene was transcribed at a moderately high level, before or after treatment with hemin. Based on these data, they suggest that the lack of expression of the endogenous β-globin gene in K562 cells does not result from an alteration in the gene itself and may not result from a lack of factor(s) necessary for β-lobin gene transcription. Retroviral-mediated transfer of the human β-globin gene may, however, uniquely influence expression of the gene K562 cells

  2. Influence of the blood glucose level on the development of retinopathy of prematurity in extremely premature children

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    Galina V. Nicolaeva

    2015-08-01

    Full Text Available ABSTRACTPurpose:To investigate the influence of the blood glucose level on the development of retinopathy of prematurity (ROP in extremely premature infants.Methods:Sixty-four premature infants with a gestational age of less than 30 weeks and a birth weight of less than 1500 g were included in the study. Children without ROP were allocated to Group 1 (n=14, gestational age 28.6 ± 1.4 weeks, birth weight 1162 ± 322 g, and children with spontaneous regression of ROP were allocated to Group 2 (n=32, gestational age 26.5 ± 1.2 weeks, birth weight 905 ± 224 g. Children with progressive ROP who underwent laser treatment were included in Group 3 (n=18, gestational age 25.4 ± 0.7 weeks, birth weight 763 ± 138 g. The glucose level in the capillary blood of the premature infants was monitored daily during the first 3 weeks of life. A complete ophthalmological screening was performed from the age of 1 month. The nonparametric signed-rank Wilcoxon-Mann-Whitney test was used for statistical analysis.Results:The mean blood glucose level was 7.43 ± 2.6 mmol/L in Group 1, 7.8 ± 2.7 mmol/L in Group 2, and 6.7 ± 2.6 mmol/L in Group 3. There were no significant differences in the blood glucose levels between children with and without ROP, and also between children with spontaneously regressing ROP and progressive ROP (p>0.05. Additionally, there were no significant differences in the blood glucose levels measured at the first, second, and third weeks of life (p>0.05.Conclusion:The blood glucose level is not related to the development of ROP nor with its progression or regression. The glycemic level cannot be considered as a risk factor for ROP, but reflects the severity of newborns’ somatic condition and morphofunctional immaturity.

  3. Resting-state functional connectivity differences in premature children

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    Eswar Damaraju

    2010-06-01

    Full Text Available We examine the coherence in the spontaneous brain activity of sleeping children as measured by the blood oxygenation level dependent (BOLD functional magnetic resonance imaging (fMRI signals. The results are described in terms of resting-state networks (RSN and their properties. More specifically, in this study we examine the effect of severe prematurity on the spatial location of the visual, temporal, motor, basal ganglia, and the default mode networks, the temporal response properties of each of these networks, and the functional connectivity between them. Our results suggest that the anatomical locations of the RSNs are well developed by 18 months of age and their spatial locations are not distinguishable between premature and term born infants at 18 months or at 36 months, with the exception of small spatial differences noted in the basal ganglia area and the visual cortex. The two major differences between term and preterm children were present at 36 but not 18 months and include: 1 increased spectral energy in the low frequency range (0.01 – 0.06 Hz for pre-term children in the basal ganglia component, and 2 stronger connectivity between RSNs in term children. We speculate that children born very prematurely are vulnerable to injury resulting in weaker connectivity between resting state networks by 36 months of age. Further work is required to determine whether this could be a clinically useful tool to identify children at risk of developmental delay related to premature birth.

  4. Indices of Neonatal Prematurity as Discriminators of Development in Middle Childhood

    Science.gov (United States)

    Taub, Harvey B.; And Others

    1977-01-01

    The comparative value of various parameters of neonatal prematurity for differentiating intellective, scholastic, and social functioning in middle childhood was assessed for a sample of 38 prematurely born and 26 maturely born subjects aged 7 to 9.5 years. (Author/JMB)

  5. Stress-induced Premature Promotes Prostate Cancer Growth and Metastasis through Alteration of Microenvironment

    Science.gov (United States)

    2012-01-01

    comprised of NF-YA, -YB and -YC proteins. NF- Y can interact with p53 to transcriptionally repress specific genes , including Cdc2 and Chk2 (Yun et al...cells already have lowered p53 (Figure 1e). NF- Y A–C proteins bind p53 and suppress transcrip- tion of target genes involved in cell cycle regulation...regulation in H(2)O(2)- induced premature senescence of human diploid fibroblasts and regulatory control exerted by the papilloma virus E6 and E7

  6. Expression of Leukemia/Lymphoma-Related Factor (LRF/POKEMON) in Human Breast Carcinoma and Other Cancers

    Science.gov (United States)

    Aggarwal, Anshu; Hunter, William J.; Aggarwal, Himanshu; Silva, Edibaldo D.; Davey, Mary S.; Murphy, Richard F.; Agrawal, Devendra K.

    2010-01-01

    The POK family of proteins plays an important role in not only embryonic development and cell differentiation, but also in oncogenesis. Leukemia/lymphoma-related factor (LRF) belongs to the POK family of transcriptional repressors and is also known as POK erythroid myeloid ontogenic factor (POKEMON), which binds to short transcripts of HIV-1 (FBI-1) and TTF-1 interacting peptide (TIP21). Its oncogenic role is known only in lymphoma, non-small cell lung carcinoma, and malignant gliomas. The functional expression of LRF in human breast carcinoma has not yet been confirmed. The aim of this study was to investigate and compare the expression of LRF in human breast cancer tissues and other human tumors. The expression of LRF mRNA transcripts and protein was observed in twenty human benign and malignant breast biopsy tissues. Expression of LRF was observed in several formalin-fixed tissues by immunohistochemistry and immunofluorescence. All malignant breast tissues expressed mRNA transcripts and protein for LRF. However, 40% and 15% benign breast biopsy tissues expressed LRF mRNA transcripts and protein, respectively. The overall expression of LRF mRNA transcripts and total protein was significantly more in malignant breast tissues than the benign breast tissues. LRF expression was also observed in the nuclei of human colon, renal, lung, hepatocellular carcinomas and thymoma tumor cells. In general, a significantly higher expression of LRF was seen in malignant tissues than in the corresponding benign or normal tissue. Further studies are warranted to determine the malignant role of LRF in human breast carcinoma. PMID:20471975

  7. Prematurity Stereotype: Effects of Labeling on Adults' Perceptions of Infants.

    Science.gov (United States)

    Stern, Marilyn; Hildebrandt, Katherine A.

    1984-01-01

    Two studies were conducted in which college students and mothers were asked to rate unfamiliar infants shown on videotapes. Infants were described as either full-term or premature and as either male or female. Infants labeled premature were rated more negatively than those labeled full-term, but infants labeled male and female were rated…

  8. Orphan nuclear receptor Nur77 participates in human apolipoprotein A5 gene expression

    International Nuclear Information System (INIS)

    Song, Kwang-Hoon

    2010-01-01

    The orphan nuclear receptor Nur77 (NR4A1) has been reported to play a crucial role in the modulation of diverse metabolic processes in liver. Here, we reported the identification of human apolipoprotein A5 (ApoA5), which implicated in lowering plasma triglyceride levels, as a novel target gene of Nur77. Nur77 induced the human ApoA5 promoter activity. Using 5'-deletion and mutagenesis of human ApoA5 promoter analysis and chromatin immunoprecipitation assays, it was shown that Nur77 directly regulated human ApoA5 gene expression by binding to a Nur77 response element (AAAGGTCA) located in the proximal human ApoA5 promoter region. In addition, we demonstrated that blocking of Nur77 transcriptional activity via overexpression of dominant negative Nur77 suppressed human ApoA5 promoter activity and mRNA expression in human hepatoma cells, HepG2. Taken together, our results demonstrated that Nur77 is a novel regulator of human ApoA5 gene expression and provide a new insight into the role of this orphan nuclear receptor in lipoprotein metabolism and triglyceride homeostasis.

  9. Orphan nuclear receptor Nur77 participates in human apolipoprotein A5 gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Song, Kwang-Hoon, E-mail: ksong@kiom.re.kr [Korea Institute of Oriental Medicine, Daejeon 305-811 (Korea, Republic of)

    2010-01-29

    The orphan nuclear receptor Nur77 (NR4A1) has been reported to play a crucial role in the modulation of diverse metabolic processes in liver. Here, we reported the identification of human apolipoprotein A5 (ApoA5), which implicated in lowering plasma triglyceride levels, as a novel target gene of Nur77. Nur77 induced the human ApoA5 promoter activity. Using 5'-deletion and mutagenesis of human ApoA5 promoter analysis and chromatin immunoprecipitation assays, it was shown that Nur77 directly regulated human ApoA5 gene expression by binding to a Nur77 response element (AAAGGTCA) located in the proximal human ApoA5 promoter region. In addition, we demonstrated that blocking of Nur77 transcriptional activity via overexpression of dominant negative Nur77 suppressed human ApoA5 promoter activity and mRNA expression in human hepatoma cells, HepG2. Taken together, our results demonstrated that Nur77 is a novel regulator of human ApoA5 gene expression and provide a new insight into the role of this orphan nuclear receptor in lipoprotein metabolism and triglyceride homeostasis.

  10. Family history of premature death and risk of early onset cardiovascular disease.

    Science.gov (United States)

    Ranthe, Mattis Flyvholm; Carstensen, Lisbeth; Oyen, Nina; Tfelt-Hansen, Jacob; Christiansen, Michael; McKenna, William J; Wohlfahrt, Jan; Melbye, Mads; Boyd, Heather A

    2012-08-28

    The purpose of this study was to examine the effect of a family history of premature death, cardiovascular death in particular, on the risk of early cardiovascular disease. Studies suggest that fatal cardiovascular events and less severe cardiovascular diseases may co-occur in families. Consequently, a family history of premature death may indicate a familial cardiac frailty that predisposes to early cardiovascular disease. We ascertained family history of premature death (age Denmark from 1950 to 2008 and followed this cohort for early cardiovascular disease (age history of premature cardiovascular death in first-degree relatives were 1.72 (95% confidence interval [CI]: 1.68 to 1.77), 2.21 (95% CI: 2.11 to 2.31), and 1.94 (95% CI: 1.70 to 2.20), respectively. With ≥2 cardiovascular deaths in a family, corresponding IRRs were 3.30 (95% CI: 2.77 to 3.94), 5.00 (95% CI: 3.87 to 6.45), and 6.18 (95% CI: 3.32 to 11.50). The IRR for any early cardiovascular disease given a family history of premature noncardiovascular death was significantly lower, 1.12 (95% CI: 1.10 to 1.14) (p(cardiac vs. noncardiac) history of premature cardiovascular death was consistently and significantly associated with a risk of early cardiovascular disease, suggesting an inherited cardiac vulnerability. These results should be kept in mind when assessing cardiovascular disease risk in persons with a family history of premature cardiovascular death. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  11. Fetal blood vessel count increases in compensation of hypoxia in premature placentas

    Directory of Open Access Journals (Sweden)

    K. Kartini

    2015-04-01

    Full Text Available Background Prematurity refers to live births before 37 weeks of gestation, wherein the baby is born before the body and its organ systems achieve perfect maturity, and this disorder is still a global problem. The high incidence of prematurity is a problem in developing and also in developed countries. Certain conditions accompanying pregnancies like preeclampsia, infection, and placental insufficiency, may trigger uterine hypoxia, causing premature birth. The placental condition is related to the intra-uterine fetal condition. In prolonged placental hypoxia, there occurs a compensatory mechanism, i.e. an increase in placental angiogenesis. This study aimed to evaluate the effect of hypoxia on fetal blood vessel count as compensatory mechanism for tissue hypoxia. Methods An observational-analytical cross-sectional design using paraffin blocks of conserved premature placentas, comprising 31 samples of hypoxic premature placentas and 28 samples of non-hypoxic premature placentas, selected using non-random consecutive sampling. The samples were made into slides and stained with hematoxylin-eosin for assessment of histological structure, including fetal blood vessel count and integrity, villus conditions, syncytiotrophoblastic nuclear changes, and syncytiotrophoblastic nuclear aggregation. Mann-Whitney test was used to compare the difference of blood vessel count between groups. Results Assessment of histological structure showed a significant increase in fetal blood vessel count in the hypoxic group [8.00 (5-15] as compared with the non-hypoxic group [7.50 (3-15]. Conclusion The hypoxia in premature placentas caused an increase in the number of fetal blood vessels as a form of compensation for disturbed oxygen homeostasis.

  12. Fetal blood vessel count increases in compensation of hypoxia in premature placentas

    Directory of Open Access Journals (Sweden)

    K Kartini

    2016-02-01

    Full Text Available BACKGROUND Prematurity refers to live births before 37 weeks of gestation, wherein the baby is born before the body and its organ systems achieve perfect maturity, and this disorder is still a global problem. The high incidence of prematurity is a problem in developing and also in developed countries. Certain conditions accompanying pregnancies like preeclampsia, infection, and placental insufficiency, may trigger uterine hypoxia, causing premature birth. The placental condition is related to the intra-uterine fetal condition. In prolonged placental hypoxia, there occurs a compensatory mechanism, i.e. an increase in placental angiogenesis. This study aimed to evaluate the effect of hypoxia on fetal blood vessel count as compensatory mechanism for tissue hypoxia. METHODS An observational-analytical cross-sectional design using paraffin blocks of conserved premature placentas, comprising 31 samples of hypoxic premature placentas and 28 samples of non-hypoxic premature placentas, selected using non-random consecutive sampling. The samples were made into slides and stained with hematoxylin-eosin for assessment of histological structure, including fetal blood vessel count and integrity, villus conditions, syncytiotrophoblastic nuclear changes, and syncytiotrophoblastic nuclear aggregation. Mann-Whitney test was used to compare the difference of blood vessel count between groups. RESULTS Assessment of histological structure showed a significant increase in fetal blood vessel count in the hypoxic group [8.00 (5-15] as compared with the non-hypoxic group [7.50 (3-15]. CONCLUSION The hypoxia in premature placentas caused an increase in the number of fetal blood vessels as a form of compensation for disturbed oxygen homeostasis.

  13. Prevalence and outcomes of laser treatment of aggressive posterior retinopathy of prematurity.

    Science.gov (United States)

    Gunn, David J; Cartwright, David W; Gole, Glen A

    2014-07-01

    To describe outcomes in a cohort of extremely premature infants treated for aggressive posterior retinopathy of prematurity by diode laser panretinal photocoagulation. Retrospective study. Fifteen eyes in eight infants. A review was carried out on infants between 23 and 25.6 weeks gestational age admitted to The Royal Brisbane and Women's Hospital neonatal intensive care unit between 1992 and 2009. Success of treatment, visual and refractive outcomes. Five hundred fifty-four infants were admitted to neonatal intensive care unit, 373 survived till screening, and 304 had retinopathy of prematurity. Sixty-six infants required treatment, and eight of these had aggressive posterior retinopathy of prematurity (2.5% of all infants with retinopathy of prematurity). Mean gestational age was 24.2 weeks, mean birthweight was 634 g, and treatment occurred at mean 34.1 weeks post-menstrual age. The mean total number of burns per eye was 2967. Five of 15 treated eyes required retreatment. Two patients subsequently died of unrelated causes. Regression occurred in 9 of 11 remaining eyes; one eye progressed to stage 4b and another to stage 5 retinopathy of prematurity. Vitrectomy was performed in two eyes. Five eyes had 6/12 vision, one had 3/60, and three had no perception of light. Of the remaining two eyes, one had good fixation and the other had poor fixation. Despite good structural outcomes, visual outcomes for conventional laser treatment of aggressive posterior retinopathy of prematurity are poor. © 2013 Royal Australian and New Zealand College of Ophthalmologists.

  14. Music Therapy with Premature Infants

    Science.gov (United States)

    Standley, Jayne

    2003-01-01

    Over 20 years of research and clinical practice in music therapy with premature infants has been compiled into this text designed for Board Certified Music Therapists specializing in Neonatal Intensive Care clinical services, for NICU medical staff incorporating research-based music therapy into developmental care plans, and for parents of…

  15. Extensive changes in the expression of the opioid genes between humans and chimpanzees.

    Science.gov (United States)

    Cruz-Gordillo, Peter; Fedrigo, Olivier; Wray, Gregory A; Babbitt, Courtney C

    2010-01-01

    The various means by which the body perceives, transmits, and resolves the experiences of pain and nociception are mediated by a host of molecules, including neuropeptides within the opioid gene signaling pathway. The peptide ligands and receptors encoded by this group of genes have been linked to behavioral disorders as well as a number of psychiatric affective disorders. Our aim was to explore the recent evolutionary history of these two gene families by taking a comparative genomics approach, specifically through a comparison between humans and chimpanzees. Our analyses indicate differential expression of these genes between the two species, more than expected based on genome-wide comparisons, indicating that differential expression is pervasive among the opioid genes. Of the 8 family members, three genes showed significant expression differences (PENK, PNOC, and OPRL1), with two others marginally significant (OPRM1 and OPRD1). Accelerated substitution rates along human and chimpanzee lineages within the putative regulatory regions of OPRM1, POMC, and PDYN between the human and chimpanzee branches are consistent with positive selection. Collectively, these results suggest that there may have been a selective advantage to modulating the expression of the opioid genes in humans compared with our closest living relatives. Information about the cognitive roles mediated by these genes in humans may help to elucidate the trait consequences of these putatively adaptive expression changes. Copyright © 2010 S. Karger AG, Basel.

  16. Expression of aquaporin8 in human astrocytomas: Correlation with pathologic grade

    International Nuclear Information System (INIS)

    Zhu, Shu-juan; Wang, Ke-jian; Gan, Sheng-wei; Xu, Jin; Xu, Shi-ye; Sun, Shan-quan

    2013-01-01

    Highlights: •AQP8 is mainly distributed in the cytoplasm of human astrocytoma cells. •AQP8 over-expressed in human astrocytomas, especially glioblastoma. •The up-regulation of AQP8 is related to the pathological grade of human astrocytomas. •AQP8 may contribute to the growth and proliferation of astrocytomas. -- Abstract: Aquaporin8 (AQP8), a member of the aquaporin (AQP) protein family, is weakly distributed in mammalian brains. Previous studies on AQP8 have focused mainly on the digestive and the reproductive systems. AQP8 has a pivotal role in keeping the fluid and electrolyte balance. In this study, we investigated the expression changes of AQP8 in 75 cases of human brain astrocytic tumors using immunohistochemistry, Western blotting, and reverse transcription polymerase chain reaction. The results demonstrated that AQP8 was mainly distributed in the cytoplasm of astrocytoma cells. The expression levels and immunoreactive score of AQP8 protein and mRNA increased in low-grade astrocytomas, and further increased in high-grade astrocytomas, especially in glioblastoma. Therefore, AQP8 may contribute to the proliferation of astrocytomas, and may be a biomarker and candidate therapy target for patients with astrocytomas

  17. Expression of aquaporin8 in human astrocytomas: Correlation with pathologic grade

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Shu-juan; Wang, Ke-jian; Gan, Sheng-wei; Xu, Jin; Xu, Shi-ye; Sun, Shan-quan, E-mail: sunsq2151@cqmu.edu.cn

    2013-10-11

    Highlights: •AQP8 is mainly distributed in the cytoplasm of human astrocytoma cells. •AQP8 over-expressed in human astrocytomas, especially glioblastoma. •The up-regulation of AQP8 is related to the pathological grade of human astrocytomas. •AQP8 may contribute to the growth and proliferation of astrocytomas. -- Abstract: Aquaporin8 (AQP8), a member of the aquaporin (AQP) protein family, is weakly distributed in mammalian brains. Previous studies on AQP8 have focused mainly on the digestive and the reproductive systems. AQP8 has a pivotal role in keeping the fluid and electrolyte balance. In this study, we investigated the expression changes of AQP8 in 75 cases of human brain astrocytic tumors using immunohistochemistry, Western blotting, and reverse transcription polymerase chain reaction. The results demonstrated that AQP8 was mainly distributed in the cytoplasm of astrocytoma cells. The expression levels and immunoreactive score of AQP8 protein and mRNA increased in low-grade astrocytomas, and further increased in high-grade astrocytomas, especially in glioblastoma. Therefore, AQP8 may contribute to the proliferation of astrocytomas, and may be a biomarker and candidate therapy target for patients with astrocytomas.

  18. Transcervical intrapartum amnioinfusion for preterm premature rupture of the membranes.

    Science.gov (United States)

    Puertas, Alberto; Tirado, Pilar; Pérez, Isabel; López, María S; Montoya, Francisco; Cañizares, José M; Miranda, José A

    2007-03-01

    To investigate the effect of transcervical amnioinfusion on the management of labour and neonatal outcomes in preterm premature rupture of the membranes. This clinical trial included 86 patients with premature rupture of the membranes between weeks 27 and 35 of gestation. Patients were randomly assigned to receive amnioinfusion via a two-way catheter or to the control group. Clinical management was otherwise the same in both groups. Amnioinfusion decreased the frequency of variable decelerations in fetal heart rate (27.9% versus 53.5%, pamnioinfusion for preterm premature rupture of the membranes reduced the number of interventions needed because of nonreassuring fetal status, and improved neonatal gasometric values without increasing maternal or fetal morbidity.

  19. Expressive Writing: Enhancing the Emotional Intelligence of Human Services Majors

    Science.gov (United States)

    Castillo, Yuleinys; Fischer, Jerome M.

    2017-01-01

    The skills and tasks in the human services field are highly connected to emotional intelligence abilities. The purpose of the study was to investigate the effect of an expressive writing program involving human service students in an undergraduate rehabilitation services course. The program was developed to enhance their emotional intelligence.…

  20. Aging of intrauterine tissues in spontaneous preterm birth and preterm premature rupture of the membranes: A systematic review of the literature.

    Science.gov (United States)

    Polettini, J; Dutta, E H; Behnia, F; Saade, G R; Torloni, M R; Menon, R

    2015-09-01

    Many adverse pregnancy outcomes (APOs), including spontaneous preterm birth (PTB), are associated with placental dysfunction. Recent clinical and experimental evidences suggest that premature aging of the placenta may be involved in these events. Although placental aging is a well-known concept, the mechanisms of aging during normal pregnancy and premature aging in APOs are still unclear. This review was conducted to assess the knowledge on placental aging related biochemical changes leading to placental dysfunction in PTB and/or preterm premature rupture of membranes (pPROM). We performed a systematic review of studies published over the last 50 years in two electronic databases (Pubmed and Embase) on placental aging and PTB or pPROM. The search yielded 554 citations, 30 relevant studies were selected for full-text review and three were included in the review. Only one study reported oxidative stress-related aging and degenerative changes in human placental membranes and telomere length reduction in fetal cells as part of PTB and/or pPROM mechanisms. Similarly, two animal studies reported findings of decidual senescence and referred to PTB mechanisms. Placental and fetal membrane oxidative damage and telomere reduction are linked to premature aging in PTB and pPROM but the risk factors and biomolecular pathways causing this phenomenon are not established in the literature. However, no biomarkers or clinical indicators of premature aging as a pathology of PTB and pPROM have been reported. We document major knowledge gaps and propose several areas for future research to improve our understanding of premature aging linked to placental dysfunction. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Modulation of SOCS protein expression influences the interferon responsiveness of human melanoma cells

    International Nuclear Information System (INIS)

    Lesinski, Gregory B; Zimmerer, Jason M; Kreiner, Melanie; Trefry, John; Bill, Matthew A; Young, Gregory S; Becknell, Brian; Carson, William E III

    2010-01-01

    Endogenously produced interferons can regulate the growth of melanoma cells and are administered exogenously as therapeutic agents to patients with advanced cancer. We investigated the role of negative regulators of interferon signaling known as suppressors of cytokine signaling (SOCS) in mediating interferon-resistance in human melanoma cells. Basal and interferon-alpha (IFN-α) or interferon-gamma (IFN-γ)-induced expression of SOCS1 and SOCS3 proteins was evaluated by immunoblot analysis in a panel of n = 10 metastatic human melanoma cell lines, in human embryonic melanocytes (HEM), and radial or vertical growth phase melanoma cells. Over-expression of SOCS1 and SOCS3 proteins in melanoma cells was achieved using the PINCO retroviral vector, while siRNA were used to inhibit SOCS1 and SOCS3 expression. Tyr 701 -phosphorylated STAT1 (P-STAT1) was measured by intracellular flow cytometry and IFN-stimulated gene expression was measured by Real Time PCR. SOCS1 and SOCS3 proteins were expressed at basal levels in melanocytes and in all melanoma cell lines examined. Expression of the SOCS1 and SOCS3 proteins was also enhanced following stimulation of a subset of cell lines with IFN-α or IFN-γ. Over-expression of SOCS proteins in melanoma cell lines led to significant inhibition of Tyr 701 -phosphorylated STAT1 (P-STAT1) and gene expression following stimulation with IFN-α (IFIT2, OAS-1, ISG-15) or IFN-γ (IRF1). Conversely, siRNA inhibition of SOCS1 and SOCS3 expression in melanoma cells enhanced their responsiveness to interferon stimulation. These data demonstrate that SOCS proteins are expressed in human melanoma cell lines and their modulation can influence the responsiveness of melanoma cells to IFN-α and IFN-γ

  2. Premature saturation in backpropagation networks: Mechanism and necessary conditions

    International Nuclear Information System (INIS)

    Vitela, J.E.; Reifman, J.

    1997-01-01

    The mechanism that gives rise to the phenomenon of premature saturation of the output units of feedforward multilayer neural networks during training with the standard backpropagation algorithm is described. The entire process of premature saturation is characterized by three distinct stages and it is concluded that the momentum term plays the leading role in the occurrence of the phenomenon. The necessary conditions for the occurrence of premature saturation are presented and a new method is proposed, based on these conditions, that eliminates the occurrence of the phenomenon. Validity of the conditions and the proposed method are illustrated through simulation results. Three case studies are presented. The first two came from a training session for classification of three component failures in a nuclear power plant. The last case, comes from a training session for classification of welded fuel elements

  3. Why do premature newborn infants display elevated blood adenosine levels?

    Science.gov (United States)

    Panfoli, Isabella; Cassanello, Michela; Bruschettini, Matteo; Colella, Marina; Cerone, Roberto; Ravera, Silvia; Calzia, Daniela; Candiano, Giovanni; Ramenghi, Luca

    2016-05-01

    Our preliminary data show high levels of adenosine in the blood of very low birth weight (VLBW) infants, positively correlating to their prematurity (i.e. body weight class). This prompted us to look for a mechanism promoting such impressive adenosine increase. We hypothesized a correlation with oxygen challenge. In fact, it is recognized that either oxygen lack or its excess contribute to the pathogenesis of the injuries of prematurity, such as retinopathy (ROP) and periventricular white matter lesions (PWMI). The optimal concentration of oxygen for resuscitation of VLBW infants is currently under revision. We propose that the elevated adenosine blood concentrations of VLBW infants recognizes two sources. The first could be its activity-dependent release from unmyelinated brain axons. Adenosine in this respect would be an end-product of the hypometabolic VLBW newborn unmyelinated axon intensely firing in response to the environmental stimuli consequent to premature birth. Adenosine would be eventually found in the blood due to blood-brain barrier immaturity. In fact, adenosine is the primary activity-dependent signal promoting differentiation of premyelinating oligodendrocyte progenitor cells (OPC) into myelinating cells in the Central Nervous System, while inhibiting their proliferation and inhibiting synaptic function. The second, would be the ecto-cellular ATP synthesized by the endothelial cell plasmalemma exposed to ambient oxygen concentrations due to premature breathing, especially in lung. ATP would be rapidly transformed into adenosine by the ectonucleotidase activities such as NTPDase I (CD39), and NT5E (CD73). An ectopic extra-mitochondrial aerobic ATP synthetic ability was reported in many cell plasma-membranes, among which endothelial cells. The potential implications of the cited hypotheses for the neonatology area would be great. The amount of oxygen administration for reviving of newborns would find a molecular basis for its assessment. VLBW

  4. Extrauterine growth restriction: Universal problem among premature infants

    Directory of Open Access Journals (Sweden)

    Brunnella Alcantara Chagas de FREITAS

    2016-02-01

    Full Text Available ABSTRACT Objective: To analyze the growth rate of premature infants in the first weeks of life and factors associated with extrauterine growth restriction. Methods: This is a cross-sectional study of 254 premature infants in a neonatal intensive care unit conducted from January 1, 2008 to December 31, 2010. Infants who died or had malformations incompatible with life were excluded. Median weight curves according to gestational age were constructed for the first four weeks of life. The Fenton growth chart calculations provided the weight Z-scores. Extrauterine growth restriction was defined as corrected weight-for-age Z-score ≤-2. Perinatal, morbidity, and health care variables were analyzed. The Poisson regression model yielded the prevalenceratios . Associations between extrauterine growth restriction and the perinatal, morbidity, and care variables were investigated. Poisson regression controlled possible confounding factors. Results: The frequency of extrauterine growth restriction was 24.0%. Most (85.0% small-for-gestational-age infants developed extrauterine growth restriction; 55.3% of extrauterine growth restriction cases involved small-for-gestational-age infants. Premature infants with gestational age >32 weeks did not recover the median birth weight until the third week of life and had a higher frequency of small-for-gestational-age. The Z-scores of non-small-for-gestational-age infants decreased more after birth than those of small-for-gestational-age infants. extrauterine growth restriction was associated with small-for-gestational-age (PR=6.14; 95%CI=3.33-11.33;p <0.001 and time without enteral diet (PR=1.08; 95%CI=1.04-1.13; p =0.010. Conclusion: Extrauterine growth restriction occurs in premature infants of all gestational age. The participation of small-for-gestational-age and nutritional practices in its genesis is noteworthy. We suggest prospective studies of all premature infants. The implementation of best care practices

  5. Role of VEGF Inhibition in the Treatment of Retinopathy of Prematurity.

    Science.gov (United States)

    Eldweik, Luai; Mantagos, Iason S

    2016-01-01

    Retinopathy of prematurity (ROP) is a potentially blinding disease characterized by retinal neovascularization, which eventually can lead to tractional retinal detachment. Improvements have been made regarding the management of retinopathy of prematurity (ROP) since it was described in the Cryotherapy for Retinopathy of Prematurity study. A more appropriate time for therapeutic intervention was defined by the Early Treatment for Retinopathy of Prematurity (ETROP) trial. Advances in screening strategies with the use of digital imaging systems are now available. All of this and the use of laser photocoagulation and vitreoretinal surgery have contributed to significant increases in favorable outcomes and decreases in child blindness secondary to ROP. Recently the use of vascular endothelial growth factor (VEGF) inhibitors has been introduced to the armamentarium for the treatment of ROP. The purpose of this review article is to evaluate the role of VEGF inhibition in the treatment of ROP.

  6. Comparative expression pathway analysis of human and canine mammary tumors

    Directory of Open Access Journals (Sweden)

    Marconato Laura

    2009-03-01

    Full Text Available Abstract Background Spontaneous tumors in dog have been demonstrated to share many features with their human counterparts, including relevant molecular targets, histological appearance, genetics, biological behavior and response to conventional treatments. Mammary tumors in dog therefore provide an attractive alternative to more classical mouse models, such as transgenics or xenografts, where the tumour is artificially induced. To assess the extent to which dog tumors represent clinically significant human phenotypes, we performed the first genome-wide comparative analysis of transcriptional changes occurring in mammary tumors of the two species, with particular focus on the molecular pathways involved. Results We analyzed human and dog gene expression data derived from both tumor and normal mammary samples. By analyzing the expression levels of about ten thousand dog/human orthologous genes we observed a significant overlap of genes deregulated in the mammary tumor samples, as compared to their normal counterparts. Pathway analysis of gene expression data revealed a great degree of similarity in the perturbation of many cancer-related pathways, including the 'PI3K/AKT', 'KRAS', 'PTEN', 'WNT-beta catenin' and 'MAPK cascade'. Moreover, we show that the transcriptional relationships between different gene signatures observed in human breast cancer are largely maintained in the canine model, suggesting a close interspecies similarity in the network of cancer signalling circuitries. Conclusion Our data confirm and further strengthen the value of the canine mammary cancer model and open up new perspectives for the evaluation of novel cancer therapeutics and the development of prognostic and diagnostic biomarkers to be used in clinical studies.

  7. Productivity loss due to premature mortality caused by blood cancer: a study based on patients undergoing stem cell transplantation.

    Science.gov (United States)

    Ortega-Ortega, Marta; Oliva-Moreno, Juan; Jiménez-Aguilera, Juan de Dios; Romero-Aguilar, Antonio; Espigado-Tocino, Ildefonso

    2015-01-01

    Stem cell transplantation has been used for many years to treat haematological malignancies that could not be cured by other treatments. Despite this medical breakthrough, mortality rates remain high. Our purpose was to evaluate labour productivity losses associated with premature mortality due to blood cancer in recipients of stem cell transplantations. We collected primary data from the clinical histories of blood cancer patients who had undergone stem cell transplantation between 2006 and 2011 in two Spanish hospitals. We carried out a descriptive analysis and calculated the years of potential life lost and years of potential productive life lost. Labour productivity losses due to premature mortality were estimated using the Human Capital method. An alternative approach, the Friction Cost method, was used as part of the sensitivity analysis. Our findings suggest that, in a population of 179 transplanted and deceased patients, males and people who die between the ages of 30 and 49 years generate higher labour productivity losses. The estimated loss amounts to over €31.4 million using the Human Capital method (€480,152 using the Friction Cost method), which means an average of €185,855 per death. The highest labour productivity losses are produced by leukaemia. However, lymphoma generates the highest loss per death. Further efforts are needed to reduce premature mortality in blood cancer patients undergoing transplantations and reduce economic losses. Copyright © 2014 SESPAS. Published by Elsevier Espana. All rights reserved.

  8. Regulation of the human SLC25A20 expression by peroxisome proliferator-activated receptor alpha in human hepatoblastoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Tachibana, Keisuke, E-mail: nya@phs.osaka-u.ac.jp [Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); Takeuchi, Kentaro; Inada, Hirohiko [Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); Yamasaki, Daisuke [Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); The Center for Advanced Medical Engineering and Informatics, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Ishimoto, Kenji [Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Tanaka, Toshiya; Hamakubo, Takao; Sakai, Juro; Kodama, Tatsuhiko [Laboratory for System Biology and Medicine, Research Center for Advanced Science and Technology, University of Tokyo, 4-6-1 Komaba, Meguro, Tokyo 153-8904 (Japan); Doi, Takefumi [Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); The Center for Advanced Medical Engineering and Informatics, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan)

    2009-11-20

    Solute carrier family 25, member 20 (SLC25A20) is a key molecule that transfers acylcarnitine esters in exchange for free carnitine across the mitochondrial membrane in the mitochondrial {beta}-oxidation. The peroxisome proliferator-activated receptor alpha (PPAR{alpha}) is a ligand-activated transcription factor that plays an important role in the regulation of {beta}-oxidation. We previously established tetracycline-regulated human cell line that can be induced to express PPAR{alpha} and found that PPAR{alpha} induces the SLC25A20 expression. In this study, we analyzed the promoter region of the human slc25a20 gene and showed that PPAR{alpha} regulates the expression of human SLC25A20 via the peroxisome proliferator responsive element.

  9. Modulation of cytokine expression in human macrophages by endocrine-disrupting chemical Bisphenol-A

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yanzhen; Mei, Chenfang [State Key Laboratory of Applied Microbiology Southern China, Guangzhou 510070 (China); Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangdong Institute of Microbiology, Guangzhou 510070 (China); Liu, Hao [Affiliated Cancer Hospital and Cancer Research Institute, Guangzhou Medical University, Guangzhou 510095 (China); Wang, Hongsheng [Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006 (China); Zeng, Guoqu; Lin, Jianhui [State Key Laboratory of Applied Microbiology Southern China, Guangzhou 510070 (China); Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangdong Institute of Microbiology, Guangzhou 510070 (China); Xu, Meiying, E-mail: xumy@gdim.cn [State Key Laboratory of Applied Microbiology Southern China, Guangzhou 510070 (China); Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangdong Institute of Microbiology, Guangzhou 510070 (China)

    2014-09-05

    Highlights: • Effects of BPA on the cytokines expression of human macrophages were investigated. • BPA increased pro-inflammation cytokines TNF-α and IL-6 production. • BPA decreased anti-inflammation IL-10 and TGF-β production. • ERα/β/ERK/NF-κB signaling involved in BPA-mediated cytokines expression. - Abstract: Exposure to environmental endocrine-disrupting chemical Bisphenol-A (BPA) is often associated with dysregulated immune homeostasis, but the mechanisms remain unclear. In the present study, the effects of BPA on the cytokines responses of human macrophages were investigated. Treatment with BPA increased pro-inflammation cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) production, but decreased anti-inflammation cytokines interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) production in THP1 macrophages, as well as in primary human macrophages. BPA effected cytokines expression through estrogen receptor α/β (ERα/β)-dependent mechanism with the evidence of ERα/β antagonist reversed the expression of cytokines. We also identified that activation of extracellular regulated protein kinases (ERK)/nuclear factor κB (NF-κB) signal cascade marked the effects of BPA on cytokines expression. Our results indicated that BPA effected inflammatory responses of macrophages via modulating of cytokines expression, and provided a new insight into the link between exposure to BPA and human health.

  10. Modulation of cytokine expression in human macrophages by endocrine-disrupting chemical Bisphenol-A

    International Nuclear Information System (INIS)

    Liu, Yanzhen; Mei, Chenfang; Liu, Hao; Wang, Hongsheng; Zeng, Guoqu; Lin, Jianhui; Xu, Meiying

    2014-01-01

    Highlights: • Effects of BPA on the cytokines expression of human macrophages were investigated. • BPA increased pro-inflammation cytokines TNF-α and IL-6 production. • BPA decreased anti-inflammation IL-10 and TGF-β production. • ERα/β/ERK/NF-κB signaling involved in BPA-mediated cytokines expression. - Abstract: Exposure to environmental endocrine-disrupting chemical Bisphenol-A (BPA) is often associated with dysregulated immune homeostasis, but the mechanisms remain unclear. In the present study, the effects of BPA on the cytokines responses of human macrophages were investigated. Treatment with BPA increased pro-inflammation cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) production, but decreased anti-inflammation cytokines interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) production in THP1 macrophages, as well as in primary human macrophages. BPA effected cytokines expression through estrogen receptor α/β (ERα/β)-dependent mechanism with the evidence of ERα/β antagonist reversed the expression of cytokines. We also identified that activation of extracellular regulated protein kinases (ERK)/nuclear factor κB (NF-κB) signal cascade marked the effects of BPA on cytokines expression. Our results indicated that BPA effected inflammatory responses of macrophages via modulating of cytokines expression, and provided a new insight into the link between exposure to BPA and human health

  11. Hospitalized Premature Infants Are Colonized by Related Bacterial Strains with Distinct Proteomic Profiles

    Directory of Open Access Journals (Sweden)

    Christopher T. Brown

    2018-04-01

    Full Text Available During the first weeks of life, microbial colonization of the gut impacts human immune system maturation and other developmental processes. In premature infants, aberrant colonization has been implicated in the onset of necrotizing enterocolitis (NEC, a life-threatening intestinal disease. To study the premature infant gut colonization process, genome-resolved metagenomics was conducted on 343 fecal samples collected during the first 3 months of life from 35 premature infants housed in a neonatal intensive care unit, 14 of whom developed NEC, and metaproteomic measurements were made on 87 samples. Microbial community composition and proteomic profiles remained relatively stable on the time scale of a week, but the proteome was more variable. Although genetically similar organisms colonized many infants, most infants were colonized by distinct strains with metabolic profiles that could be distinguished using metaproteomics. Microbiome composition correlated with infant, antibiotics administration, and NEC diagnosis. Communities were found to cluster into seven primary types, and community type switched within infants, sometimes multiple times. Interestingly, some communities sampled from the same infant at subsequent time points clustered with those of other infants. In some cases, switches preceded onset of NEC; however, no species or community type could account for NEC across the majority of infants. In addition to a correlation of protein abundances with organism replication rates, we found that organism proteomes correlated with overall community composition. Thus, this genome-resolved proteomics study demonstrated that the contributions of individual organisms to microbiome development depend on microbial community context.

  12. Hospitalized Premature Infants Are Colonized by Related Bacterial Strains with Distinct Proteomic Profiles

    Science.gov (United States)

    Xiong, Weili; Olm, Matthew R.; Thomas, Brian C.; Baker, Robyn; Firek, Brian; Morowitz, Michael J.; Hettich, Robert L.

    2018-01-01

    ABSTRACT During the first weeks of life, microbial colonization of the gut impacts human immune system maturation and other developmental processes. In premature infants, aberrant colonization has been implicated in the onset of necrotizing enterocolitis (NEC), a life-threatening intestinal disease. To study the premature infant gut colonization process, genome-resolved metagenomics was conducted on 343 fecal samples collected during the first 3 months of life from 35 premature infants housed in a neonatal intensive care unit, 14 of whom developed NEC, and metaproteomic measurements were made on 87 samples. Microbial community composition and proteomic profiles remained relatively stable on the time scale of a week, but the proteome was more variable. Although genetically similar organisms colonized many infants, most infants were colonized by distinct strains with metabolic profiles that could be distinguished using metaproteomics. Microbiome composition correlated with infant, antibiotics administration, and NEC diagnosis. Communities were found to cluster into seven primary types, and community type switched within infants, sometimes multiple times. Interestingly, some communities sampled from the same infant at subsequent time points clustered with those of other infants. In some cases, switches preceded onset of NEC; however, no species or community type could account for NEC across the majority of infants. In addition to a correlation of protein abundances with organism replication rates, we found that organism proteomes correlated with overall community composition. Thus, this genome-resolved proteomics study demonstrated that the contributions of individual organisms to microbiome development depend on microbial community context. PMID:29636439

  13. PREMATURE RUPTURE OF THE MEMBRANES*

    African Journals Online (AJOL)

    In patients presenting with premature rupture of the membranes there are two factors which influence the foetal morbidity and mortality. These factors are prema- turity and intra-uterine infection. The purpose of this analysis was to elucidate which factor carried the greater risk to the foetus. Recently there has been a spate of.

  14. Correction of murine mucopolysaccharidosis VII by a human. beta. -glucuronidase transgene

    Energy Technology Data Exchange (ETDEWEB)

    Kyle, J.W.; Vogler, C.; Hoffmann, J.W.; Sly, W.S. (St. Louis Univ. School of Medicine, MO (USA)); Birkenmeier, E.H.; Gwynn, B. (Jackson Laboratory, Bar Harbor, ME (USA))

    1990-05-01

    The authors recently described a murine model for mucopolysaccharidosis VII in mice that have an inherited deficiency of {beta}-glucuronidase. Affected mice, of genotype gus{sup mps}/gus{sup mps}, present clinical manifestations similar to those of humans with mucopolysaccharidosis VII (Sly syndrome) and are shown here to have secondary elevations of other lysosomal enzymes. The mucopolysaccharidosis VII phenotype in both species includes dwarfism, skeletal deformities, and premature death. Lysosome storage is visualized within enlarged vesicles and correlates biochemically with accumulation of undegraded and partially degraded glycosaminoglycans. In this report they describe the consequences of introducing the human {beta}-glucuronidase gene, GUSB, into gus{sup mps}/gus{sup mps} mice that produce virtually no murine {beta}-glucuronidase. Transgenic mice homozygous for the mucopolysaccharidosis VII mutation expressed high levels of human {beta}-glucuronidase activity in all tissues examined and were phenotypically normal. Biochemically, both the intralysosomal storage of glycosaminoglycans and the secondary elevation of other acid hydrolases were corrected. These findings demonstrate that the GUSB transgene is expressed in gus{sup mps}/gus{sup mps} mice and that human {beta}-glucuronidase corrects the murine mucopolysaccharidosis storage disease.

  15. Bibliometric analysis of theses and dissertations on prematurity in the Capes database.

    Science.gov (United States)

    Pizzani, Luciana; Lopes, Juliana de Fátima; Manzini, Mariana Gurian; Martinez, Claudia Maria Simões

    2012-01-01

    To perform a bibliometric analysis of theses and dissertations on prematurity in the Capes database from 1987 to 2009. This is a descriptive study that used the bibliometric approach for the production of indicators of scientific production. Operationally, the methodology was developed in four steps: 1) construction of the theoretical framework; 2) data collection sourced from the abstracts of theses and dissertations available in the Capes Thesis Database which presented the issue of prematurity in the period 1987 to 2009; 3) organization, processing and construction of bibliometric indicators; 4) analysis and interpretation of results. Increase in the scientific literature on prematurity during the period 1987 to 2009; production is represented mostly by dissertations; the institution that received prominence was the Universidade de São Paulo. The studies are directed toward the low birth weight and very low birth weight preterm newborn, encompassing the social, biological and multifactorial causes of prematurity. There is a qualified, diverse and substantial scientific literature on prematurity developed in various graduate programs of higher education institutions in Brazil.

  16. Computer-Assisted Digital Image Analysis of Plus Disease in Retinopathy of Prematurity.

    Science.gov (United States)

    Kemp, Pavlina S; VanderVeen, Deborah K

    2016-01-01

    The objective of this study is to review the current state and role of computer-assisted analysis in diagnosis of plus disease in retinopathy of prematurity. Diagnosis and documentation of retinopathy of prematurity are increasingly being supplemented by digital imaging. The incorporation of computer-aided techniques has the potential to add valuable information and standardization regarding the presence of plus disease, an important criterion in deciding the necessity of treatment of vision-threatening retinopathy of prematurity. A review of literature found that several techniques have been published examining the process and role of computer aided analysis of plus disease in retinopathy of prematurity. These techniques use semiautomated image analysis techniques to evaluate retinal vascular dilation and tortuosity, using calculated parameters to evaluate presence or absence of plus disease. These values are then compared with expert consensus. The study concludes that computer-aided image analysis has the potential to use quantitative and objective criteria to act as a supplemental tool in evaluating for plus disease in the setting of retinopathy of prematurity.

  17. AXIAL MODIFICATIONS OF PERMANENT LOWER MOLARS AFTER PREMATURE LOSSES OF TEMPORARY MOLARS.

    Science.gov (United States)

    Cernei, E R; Mavru, R B; Zetu, Irina Nicoleta

    2016-01-01

    The aim of our study was to determine the impact of premature loss of temporary lower molars upon the longitudinal axis of the first and second permanent molars. The study groups included 61 patients, 6-9 year olds with premature loss of primary molars and a control group of 24 patients with intact temporary teeth. We evaluated the angle between longitudinal axis of first and second lower permanent molars and occlusal plane. It was observed that premature loss of lower second deciduous molar modifies more the vertical axis of first and second permanent molars than the premature loss of first lower primary molar. Reducing space occurs mainly through mesial inclination of molars that separates the edentulous breach. Temporary loss of both lower first molars on the same quadrant causes an accelerated eruption of both premolars increasing the prevalence of eruption sequence: "4-5-3-7". The preservation of the occlusal morpho-functional complex using space maintainers mainly when the premature loss of the second primary molars occurs is the best interceptive treatment option.

  18. Decreased risk of prematurity after elective repeat cesarean delivery in Hispanics.

    Science.gov (United States)

    Vilchez, Gustavo; Chelliah, Anushka; Bratley, Elaine; Bahado-Singh, Ray; Sokol, Robert

    2015-01-01

    The current recommendation is to delay elective repeat cesarean deliveries (ERCD) until 39 weeks to decrease prematurity risks. Prior reports suggest accelerated maturity of fetuses according to race (African-Americans and Asians). To analyze the effect of the Hispanic ethnicity on the prematurity risk after ERCD. The US Natality Database from 2004 to 2008 was reviewed. Inclusion criteria were singleton delivery, no trial of labor, repeat cesarean. Exclusion criteria were fetal anomalies, history of diabetes/hypertension related disorders. Outcomes analyzed were Apgar score, assisted ventilation, intensive care admission, surfactant/antibiotic use and seizures. Two groups were identified: non-Hispanic Whites (NHW) and Hispanic Whites (HW). Regression analysis was performed to calculate adjusted odds ratios. Deliveries at 36-40 weeks were studied with 40 weeks as the reference group. A total of 930421 ERCDs were identified, 396823 NHW and 236733 HW. For NHW, the risk of prematurity was lower at 39 weeks. For HW, there was no difference in the risks of prematurity at/beyond 38 weeks. There appears to be accelerated maturity with no increase in prematurity risk at 38 weeks in HW delivered by ERCD. Ethnicity can be considered for patient counseling and decision making regarding optimal timing of elective interventions.

  19. Regiospecific Synthesis of Ring A Fused Withaferin A Isoxazoline Analogues: Induction of Premature Senescence by W-2b in Proliferating Cancer Cells.

    Science.gov (United States)

    Rasool, Faheem; Nayak, Debasis; Katoch, Archana; Faheem, Mir Mohd; Yousuf, Syed Khalid; Hussain, Nazar; Belawal, Chetan; Satti, N K; Goswami, Anindya; Mukherjee, Debaraj

    2017-10-23

    Induction of premature senescence represents a novel functional strategy to curb the uncontrolled proliferation of malignant cancer cells. This study unveils the regiospecific synthesis of novel isoxazoline derivatives condensed to ring A of medicinal plant product Withaferin-A. Intriguingly, the cis fused products with β-oriented hydrogen exhibited excellent cytotoxic activities against proliferating human breast cancer MCF7 and colorectal cancer HCT-116 cells. The most potent derivative W-2b triggered premature senescence along with increase in senescence-associated β-galactosidase activity, G2/M cell cycle arrest, and induction of senescence-specific marker p21 Waf1/Cip1 at its sub-toxic concentration. W-2b conferred a robust increase in phosphorylation of mammalian checkpoint kinase-2 (Chk2) in cancer cells in a dose-dependent manner. Silencing of endogenous Chk2 by siRNA divulged that the amplification of p21 expression and senescence by W-2b was Chk2-dependent. Chk2 activation (either by ectopic overexpression or through treatment with W-2b) suppressed NM23-H1 signaling axis involved in cancer cell proliferation. Finally, W-2b showed excellent in vivo efficacy with 83.8% inhibition of tumor growth at a dose of 25 mg/kg, b.w. in mouse mammary carcinoma model. Our study claims that W-2b could be a potential candidate to limit aberrant cellular proliferation rendering promising improvement in the treatment regime in cancer patients.

  20. DNA methyl transferases are differentially expressed in the human anterior eye segment.

    Science.gov (United States)

    Bonnin, Nicolas; Belville, Corinne; Chiambaretta, Frédéric; Sapin, Vincent; Blanchon, Loïc

    2014-08-01

    DNA methylation is an epigenetic mark involved in the control of genes expression. Abnormal epigenetic events have been reported in human pathologies but weakly documented in eye diseases. The purpose of this study was to establish DNMT mRNA and protein expression levels in the anterior eye segment tissues and their related (primary or immortalized) cell cultures as a first step towards future in vivo and in vitro methylomic studies. Total mRNA was extracted from human cornea, conjunctiva, anterior lens capsule, trabeculum and related cell cultures (cornea epithelial, trabecular meshwork, keratocytes for primary cells; and HCE, Chang, B-3 for immortalized cells). cDNA was quantified by real-time PCR using specific primers for DNMT1, 2, 3A, 3B and 3L. Immunolocalization assays were carried out on human cornea using specific primary antibodies for DNMT1, 2 and 3A, 3B and 3L. All DNMT transcripts were detected in human cornea, conjunctiva, anterior lens capsule, trabeculum and related cells but showed statistically different expression patterns between tissues and cells. DNMT2 protein presented a specific and singular expression pattern in corneal endothelium. This study produced the first inventory of the expression patterns of DNMTs in human adult anterior eye segment. Our research highlights that DNA methylation cannot be ruled out as a way to bring new insights into well-known ocular diseases. In addition, future DNA methylation studies using various cells as experimental models need to be conducted with attention to approach the results analysis from a global tissue perspective. © 2014 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  1. Inhibition of Mitochondrial Cytochrome c Release and Suppression of Caspases by Gamma-Tocotrienol Prevent Apoptosis and Delay Aging in Stress-Induced Premature Senescence of Skin Fibroblasts

    Directory of Open Access Journals (Sweden)

    Suzana Makpol

    2012-01-01

    Full Text Available In this study, we determined the molecular mechanism of γ-tocotrienol (GTT in preventing cellular aging by focusing on its anti-apoptotic effect in stress-induced premature senescence (SIPS model of human diploid fibroblasts (HDFs. Results obtained showed that SIPS exhibited senescent-phenotypic characteristic, increased expression of senescence-associated β-galactosidase (SA β-gal and promoted G0/G1 cell cycle arrest accompanied by shortening of telomere length with decreased telomerase activity. Both SIPS and senescent HDFs shared similar apoptotic changes such as increased Annexin V-FITC positive cells, increased cytochrome c release and increased activation of caspase-9 and caspase-3 (P<0.05. GTT treatment resulted in a significant reduction of Annexin V-FITC positive cells, inhibited cytochrome c release and decreased activation of caspase-9 and caspase-3 (P<0.05. Gene expression analysis showed that GTT treatment down regulated BAX mRNA, up-regulated BCL2A1 mRNA and decreased the ratio of Bax/Bcl-2 protein expression (P<0.05 in SIPS. These findings suggested that GTT inhibits apoptosis by modulating the upstream apoptosis cascade, causing the inhibition of cytochrome c release from the mitochondria with concomitant suppression of caspase-9 and caspase-3 activation. In conclusion, GTT delays cellular senescence of human diploid fibroblasts through the inhibition of intrinsic mitochondria-mediated pathway which involved the regulation of pro- and anti-apoptotic genes and proteins.

  2. Prevalence and Determinants of Premature Menopause among Indian Women: Issues and Challenges Ahead.

    Science.gov (United States)

    Jungari, Suresh Banayya; Chauhan, Bal Govind

    2017-05-01

    Premature menopause refers to the occurrence of menopause in women less than 40 years of age. This heterogeneous disorder affects 1 percent and 0.1 percent of women less than 40 and 30 years of age, respectively. The study reported in this article attempts to understand the prevalence and determinants of premature menopause among Indian women by studying the effects of various socioeconomic indicators, such as age, education, wealth index, rural-urban settlement, work status, religion, and caste, on women. The study analyzed the National Family Health Survey-3, which is equivalent to the Demographic Health Survey in India. Bivariate and logistic regression analyses were performed to tease out the determinants of premature menopause. Results indicate that the percentage of premature menopause is very high (5.5 percent) among Indian women. Among Indian states, Andhra Pradesh women have the highest percentage of premature menopause (14.6 percent). Smoking and the nutritional status of women are strongly associated with early menopause. Furthermore, women living in rural areas and using tobacco are at a greater risk of premature menopause. © 2017 National Association of Social Workers.

  3. Mathematical modelling of thermoregulation processes for premature infants in closed convectively heated incubators.

    Science.gov (United States)

    Fraguela, Andrés; Matlalcuatzi, Francisca D; Ramos, Ángel M

    2015-02-01

    The low-weight newborns and especially the premature infants have difficulty in maintaining their temperature in the range considered to be normal. Several studies revealed the importance of thermal environment and moisture to increase the survival rate of newborns. This work models the process of heat exchange and energy balance in premature newborns during the first hours of life in a closed incubator. In addition, a control problem was proposed and solved in order to maintain thermal stability of premature newborns to increase their rate of survival and weight. For this purpose, we propose an algorithm to control the temperature inside the incubator. It takes into account the measurements of the body temperature of a premature newborn which are recorded continuously. We show that using this model the temperature of a premature newborn inside the incubator can be kept in a thermal stability range. Copyright © 2014. Published by Elsevier Ltd.

  4. Expression of androgen-binding protein (ABP) in human cardiac myocytes.

    Science.gov (United States)

    Schock, H W; Herbert, Z; Sigusch, H; Figulla, H R; Jirikowski, G F; Lotze, U

    2006-04-01

    Cardiomyocytes are known to be androgen targets. Changing systemic steroid levels are thought to be linked to various cardiac ailments, including dilated cardiomyopathy (DCM). The mode of action of gonadal steroid hormones on the human heart is unknown to date. In the present study, we used high-resolution immunocytochemistry on semithin sections (1 microm thick), IN SITU hybridization, and mass spectrometry to investigate the expression of androgen-binding protein (ABP) in human myocardial biopsies taken from male patients with DCM. We observed distinct cytoplasmic ABP immunoreactivity in a fraction of the myocytes. IN SITU hybridization with synthetic oligonucleotide probes revealed specific hybridization signals in these cells. A portion of the ABP-positive cells contained immunostaining for androgen receptor. With SELDI TOF mass spectrometry of affinity purified tissue extracts of human myocardium, we confirmed the presence of a 50 kDa protein similar to ABP. Our observations provide evidence of an intrinsic expression of ABP in human heart. ABP may be secreted from myocytes in a paracrine manner perhaps to influence the bioavailabity of gonadal steroids in myocardium.

  5. Low birthweight and prematurity in relation to paternal factors

    DEFF Research Database (Denmark)

    Basso, Olga; Olsen, Jørn; Christensen, Kaare

    1999-01-01

    BACKGROUND: The importance of paternal determinants in the occurrence of low birthweight and prematurity is not well known. We investigated these outcomes in siblings and paternal half siblings as a function of changes in putative external determinants between two births in fathers who had...... experienced the birth of a premature and/or low birthweight (PTB/LBW) infant. METHODS: All fathers who, between 1980 and 1992, had an infant born before 37 completed weeks' gestation or weighing

  6. The Severity of Retinopathy in the Extremely Premature Infants

    OpenAIRE

    Trivli, Alexandra; Polychronaki, Maria; Matalliotaki, Charoula; Papadimas, Michail; Patelarou, Athina E.; Dermitzaki, Niki; Matalliotakis, Michail

    2017-01-01

    Objective. We aimed to investigate the incidence and the severity of retinopathy of extremely premature infants and to evaluate the risk factors and outcome of the cases. Materials and Methods. Out of 200 premature births, we retrospectively reviewed 9 cases that developed ROP. We excluded cases where ROP developed in newborns > 30 weeks of gestational age and cases where medical notes were unavailable or incomplete. Topical drops of cyclopentolate 1% and phenylephrine 5% were instilled and f...

  7. Retinopathy of prematurity blindness worldwide: phenotypes in the third epidemic

    Directory of Open Access Journals (Sweden)

    Quinn GE

    2016-05-01

    Full Text Available Graham E Quinn Division of Ophthalmology, The Children’s Hospital of Philadelphia, Wood Center, Philadelphia, PA, USA Abstract: Blindness due to retinopathy of prematurity (ROP is an increasing problem worldwide as improved levels of neonatal care are provided in countries with developing neonatal intensive care units. The occurrence of ROP blindness varies dramatically with the socioeconomic development of a country. In regions with high levels of neonatal care and adequate resources, ROP blindness is largely restricted to premature infants with very low birth weight and low gestational age while in middle- and low-income countries with regional variation in technology and capacity, limited health resources may well limit the care of the premature newborn. Keywords: ROP, international, blindness

  8. Neuro-ophthalmic manifestations of prematurity

    Directory of Open Access Journals (Sweden)

    Preeti Patil Chhablani

    2014-01-01

    Full Text Available Increasing rates of preterm births coupled with better survival of these infants have resulted in higher prevalence of systemic and ocular complications associated with prematurity. In addition to retinopathy of prematurity, infants who are born preterm may suffer from severe visual impairment as a result of hypoxic ischemic encephalopathy, hypoglycemia, and other metabolic imbalances. The effect of these processes on the anterior visual pathway may result in optic atrophy, optic nerve hypoplasia or optic disc cupping and affection of the posterior visual pathway leads to cortical visual impairment (CVI. Other ocular associations include strabismus, nystagmus, and ocular motor abnormalities such as tonic down gaze and defective saccades and pursuits. Cortical and subcortical involvement also manifests as defects in functional vision and these have not yet been completely understood. Children with CVI may have visual field defects, photophobia, defective visual processing, and deficient color vision. Since most of these children also suffer from additional systemic disabilities, evaluation, and management remains a challenge. However, early diagnosis and initiation of rehabilitation therapy can prove to be of significant benefit in these children.

  9. Effects of low dose rate irradiation on life span prolongation of human premature-aging syndrome model mice

    International Nuclear Information System (INIS)

    Nomura, Takaharu

    2006-01-01

    We previously showed that Type II diabetes model mice prolonged of their life span by life long low dose rate irradiation. We also found that antioxidant function in variety tissues of some strain of mice were enhancement after low dose/low dose rate irradiation. The prolongation of life span might depend on certain damaged level of reactive oxygen species. We thought the effect of the prolongation was due to the enhancement of the antioxidant activities after irradiation. We investigated whether the enhancement of antioxidant activities after low dose rate irradiation had an effect on life span prolongation. Four-week-old female human premature-aging syndrome model mice, kl/kl (klotho) mice, which the life span of this model mouse is about 65 days, were irradiated with gamma rays at 0.35, 0.70 or 1.2 mGy/hr. The 0.70 mGy/hr-irradiated group remarkably effected on the prolongation of their life span. Some mice of the group were extremely survived for about and more 100 days. Antioxidant activities in the irradiated groups were enhancement by low dose rate irradiation, however the dependence of the dose rates were not clearly difference. These results suggest that the antioxidant activities in this model mouse were enhanced by the low dose rate irradiation, and may make it possible to prolong the life span of this mouse. (author)

  10. Drug-loaded nanoparticles induce gene expression in human pluripotent stem cell derivatives

    Science.gov (United States)

    Gajbhiye, Virendra; Escalante, Leah; Chen, Guojun; Laperle, Alex; Zheng, Qifeng; Steyer, Benjamin; Gong, Shaoqin; Saha, Krishanu

    2013-12-01

    Tissue engineering and advanced manufacturing of human stem cells requires a suite of tools to control gene expression spatiotemporally in culture. Inducible gene expression systems offer cell-extrinsic control, typically through addition of small molecules, but small molecule inducers typically contain few functional groups for further chemical modification. Doxycycline (DXC), a potent small molecule inducer of tetracycline (Tet) transgene systems, was conjugated to a hyperbranched dendritic polymer (Boltorn H40) and subsequently reacted with polyethylene glycol (PEG). The resulting PEG-H40-DXC nanoparticle exhibited pH-sensitive drug release behavior and successfully controlled gene expression in stem-cell-derived fibroblasts with a Tet-On system. While free DXC inhibited fibroblast proliferation and matrix metalloproteinase (MMP) activity, PEG-H40-DXC nanoparticles maintained higher fibroblast proliferation levels and MMP activity. The results demonstrate that the PEG-H40-DXC nanoparticle system provides an effective tool to controlling gene expression in human stem cell derivatives.Tissue engineering and advanced manufacturing of human stem cells requires a suite of tools to control gene expression spatiotemporally in culture. Inducible gene expression systems offer cell-extrinsic control, typically through addition of small molecules, but small molecule inducers typically contain few functional groups for further chemical modification. Doxycycline (DXC), a potent small molecule inducer of tetracycline (Tet) transgene systems, was conjugated to a hyperbranched dendritic polymer (Boltorn H40) and subsequently reacted with polyethylene glycol (PEG). The resulting PEG-H40-DXC nanoparticle exhibited pH-sensitive drug release behavior and successfully controlled gene expression in stem-cell-derived fibroblasts with a Tet-On system. While free DXC inhibited fibroblast proliferation and matrix metalloproteinase (MMP) activity, PEG-H40-DXC nanoparticles maintained

  11. Increased expression of aquaporin-4 in human traumatic brain injury and brain tumors

    Institute of Scientific and Technical Information of China (English)

    HU Hua; YAO Hong-tian; ZHANG Wei-ping; ZHANG LEI; DING Wei; ZHANG Shi-hong; CHEN Zhong; WEI Er-qing

    2005-01-01

    Objective: To characterize the expression of aquaporin-4 (AQP4), one of the aquaporins (AQPs), in human brain specimens from patients with traumatic brain injury or brain tumors. Methods: Nineteen human brain specimens were obtained from the patients with traumatic brain injury, brain tumors, benign meningioma or early stage hemorrhagic stroke. MRI or CT imaging was used to assess brain edema. Hematoxylin and eosin staining were used to evaluate cell damage. Immunohistochemistry was used to detect the AQP4 expression. Results: AQP4 expression was increased from 15h to at least 8 d after injury. AQP4immunoreactivity was strong around astrocytomas, ganglioglioma and metastatic adenocarcinoma. However, AQP4 immunoreactivity was only found in the centers of astrocytomas and ganglioglioma, but not in metastatic adenocarcinoma derived from lung.Conclusion: AQP4 expression increases in human brains after traumatic brain injury, within brain-derived tumors, and around brain tumors.

  12. Medical humanities as expressive of Western culture.

    Science.gov (United States)

    Hooker, Claire; Noonan, Estelle

    2011-12-01

    In this paper we articulate a growing awareness within the field of the ways in which medical humanities could be deemed expressive of Western cultural values. The authors suggest that medical humanities is culturally limited by a pedagogical and scholarly emphasis on Western cultural artefacts, as well as a tendency to enact an uncritical reliance upon foundational concepts (such as 'patient' and 'experience') within Western medicine. Both these tendencies within the field, we suggest, are underpinned by a humanistic emphasis on appreciative or receptive encounters with 'difference' among patients that may unwittingly contribute to the marginalisation of some patients and healthcare workers. While cultural difference should be acknowledged as a central preoccupation of medical humanities, we argue that the discipline must continue to expand its scholarly and critical engagements with processes of Othering in biomedicine. We suggest that such improvements are necessary in order to reflect the cultural diversification of medical humanities students, and the geographical expansion of the discipline within non-Western and/or non-Anglophone locations.

  13. Expression and regulation of the tumor suppressor, SEF, during folliculogenesis in humans and mice.

    Science.gov (United States)

    Lutwak, Ela; Price, Christopher A; Abramovich, Sagit-Sela; Rabinovitz, Shiri; Granot, Irit; Dekel, Nava; Ron, Dina

    2014-11-01

    Similar expression to FGF (Sef or IL17-RD), is a tumor suppressor and an inhibitor of growth factors as well as of pro-inflammatory cytokine signaling. In this study, we examined the regulation of Sef expression by gonadotropins during ovarian folliculogenesis. In sexually immature mice, in situ hybridization (ISH) localized Sef gene expression to early developing oocytes and granulosa cells (GC) but not to theca cells. Sef was also expressed in mouse ovarian endothelial cells, in the fallopian tube epithelium as well as in adipose tissue venules. SEF protein expression, determined by immunohistochemistry (IHC), correlated well with Sef mRNA expression in GC, while differential expression was noticed in oocytes. High Sef mRNA but undetectable SEF protein levels were observed in the oocytes of primary/secondary follicles, while an inverse correlation was found in the oocytes of preantral and small antral follicles. Sef mRNA expression dropped after pregnant mare's serum gonadotropin (PMSG) administration, peaked at 6-8 h after human chorionic gonadotropin (hCG) treatment, and declined by 12 h after this treatment. ISH and IHC localized the changes to oocytes and mural GC following PMSG treatment, whereas Sef expression increased in mural GC and declined in granulosa-lutein cells upon hCG treatment. The ovarian expression of SEF was confirmed using human samples. ISH localized SEF transcripts to human GC of antral follicles but not to corpora lutea. Furthermore, SEF mRNA was detected in human GC recovered from preovulatory follicles. These results are the first to demonstrate SEF expression in a healthy ovary during folliculogenesis. Hormonal regulation of its expression suggests that SEF may be an important factor involved in intra-ovarian control mechanisms. © 2014 Society for Reproduction and Fertility.

  14. Distribution of cellular HSV-1 receptor expression in human brain.

    Science.gov (United States)

    Lathe, Richard; Haas, Juergen G

    2017-06-01

    Herpes simplex virus type 1 (HSV-1) is a neurotropic virus linked to a range of acute and chronic neurological disorders affecting distinct regions of the brain. Unusually, HSV-1 entry into cells requires the interaction of viral proteins glycoprotein D (gD) and glycoprotein B (gB) with distinct cellular receptor proteins. Several different gD and gB receptors have been identified, including TNFRSF14/HVEM and PVRL1/nectin 1 as gD receptors and PILRA, MAG, and MYH9 as gB receptors. We investigated the expression of these receptor molecules in different areas of the adult and developing human brain using online transcriptome databases. Whereas all HSV-1 receptors showed distinct expression patterns in different brain areas, the Allan Brain Atlas (ABA) reported increased expression of both gD and gB receptors in the hippocampus. Specifically, for PVRL1, TNFRFS14, and MYH9, the differential z scores for hippocampal expression, a measure of relative levels of increased expression, rose to 2.9, 2.9, and 2.5, respectively, comparable to the z score for the archetypical hippocampus-enriched mineralocorticoid receptor (NR3C2, z = 3.1). These data were confirmed at the Human Brain Transcriptome (HBT) database, but HBT data indicate that MAG expression is also enriched in hippocampus. The HBT database allowed the developmental pattern of expression to be investigated; we report that all HSV1 receptors markedly increase in expression levels between gestation and the postnatal/adult periods. These results suggest that differential receptor expression levels of several HSV-1 gD and gB receptors in the adult hippocampus are likely to underlie the susceptibility of this brain region to HSV-1 infection.

  15. Expression of Zonulin, c-kit, and Glial Fibrillary Acidic Protein in Human Gliomas.

    Science.gov (United States)

    Skardelly, Marco; Armbruster, Franz Paul; Meixensberger, Jürgen; Hilbig, Heidegard

    2009-08-18

    The hallmarks of human malignant gliomas are their marked invasiveness and vascularity. Because angiogenesis and tumor invasion have been associated with extracellular matrix degradation and intercellular tight junctions, the involvement of zonulin in glioma biology is in the focus. We selected for histological examination five cases of glioblastoma WHO IV (nomenclature of the World Health Organization) and one case each from astrocytoma WHO III, meningioma WHO III, and meningioma WHO I as control samples. The meningioma WHO I is regarded as benign, whereas the meningioma WHO III is recognized as the transition form of malignant tumors in humans. The visualization of a newly designed antibody against human zonulin was studied in triple-labeling studies using fluorescence immunocytochemistry and compared with the expression of c-kit and glial fibrillary acidic protein in differently developed human gliomas. We found that increasing the expression of c-kit is accompanied by an increase of zonulin expression. Both are correlated to the degree of malignancy of human brain tumors. The expression of zonulin is correlated to the degradation of the blood-brain barrier as revealed by Griffonia simplicifolia lectin. In differently graded tumors, we found differently graded involvement of blood vessels in the tumor development, explaining patients' survival.

  16. Expression of cDNAs in human Natural Killer cell lines by retroviral transduction.

    Science.gov (United States)

    Miah, S M Shahjahan; Campbell, Kerry S

    2010-01-01

    Human NK-like cell lines are difficult to transfect using standard mammalian expression vectors and conventional transfection protocols, but they are susceptible to retroviral transduction as a means to introduce cDNAs. Our laboratory has exploited this technique to study a number of receptors in human NK cell lines. The method utilizes a bicistronic retroviral vector that co-expresses either drug resistance or enhanced green fluorescent protein (EGFP) in parallel with the gene of interest. After a single infection with recombinant retrovirus, transduced NK cells can be sorted for expression of EGFP or the transduced cell surface marker. Alternatively, cells expressing the transduced cDNAs can be selected for by treatment with neomycin, puromycin, or hygromycin. Using this method, the sorted/selected cells uniformly express the gene of interest and the expression is stable for many weeks of culture.

  17. The progress of prophylactic treatment in retinopathy of prematurity

    Science.gov (United States)

    Zhang, Hong-Bing; Wang, Xiao-Dong; Xu, Kun; Li, Xiao-Gang

    2018-01-01

    Retinopathy of prematurity (ROP) is a retinal vascular disorder frequently found in premature infants. Different therapeutic strategies have been developed to treat ROP. However, there are still many children with ROP suffering by severe limitations in vision or even blindness. Recently, ROP has been suggested to be caused by abnormal development of the retinal vasculature, but not simply resulted by retinal neovascularization which takes about 4 to 6wk after birth in premature infants. Thus, instead of focusing on how to reduce retinal neovascularization, understanding the pathological changes and mechanisms that occur prior to retinal neovascularization is meaningful, which may lead to identify novel target(s) for the development of novel strategy to promote the healthy growth of retinal blood vessels rather than passively waiting for the appearance of retinal neovascularization and removing it by force. In this review, we discussed recent studies about, 1) the pathogenesis prior to retinal neovascularization in oxygen-induced retinopathy (OIR; a ROP in animal model) and in premature infants with ROP; 2) the preclinical and clinical research on preventive treatment of early OIR and ROP. We will not only highlight the importance of the mechanisms and signalling pathways in regulating early stage of ROP but also will provide guidance for actively exploring novel mechanisms and discovering novel treatments for early phase OIR and ROP prior to retinal neovascularization in the future. PMID:29862189

  18. Mothers' Retrospections of Premature Childbirth.

    Science.gov (United States)

    Kalmar, Magda; And Others

    This study examined Hungarian mothers' recollections, 8 years after the birth of their premature baby, of their stress at the time of the baby's birth. Interviews were conducted with 30 mothers whose babies had been born between 30 and 37 weeks gestational age. At the time of the follow-up, all children had normal IQs and were attending normal…

  19. Level of C - reactive protein as an indicator for prognosis of premature uterine contractions.

    Science.gov (United States)

    Najat Nakishbandy, Bayar M; Barawi, Sabat A M

    2014-01-01

    high concentrations of maternal C-reactive protein have been associated with adverse pregnancy outcome, and premature uterine contraction may be predicted by elevated levels of C-reactive protein. This may ultimately be simple and cost-effective enough to introduce as a low-risk screening program. an observational case control study was performed from May 1st, 2010 to December 1st, 2010 at Maternity Teaching Hospital-Erbil/ Kurdistan Region/ Iraq. The sample size was (200) cases. Hundred of them were presented with premature uterine contractions at 24(+0)-36(+6) weeks. The other hundred were control group at same gestational ages. The level of C-reactive protein was determined in both groups and both groups were followed till delivery. (93) out of (100) women with premature uterine contractions had elevated level of C-Reactive protein and 91% delivered prematurely while in the control group only (9) out of (100) women had elevated level of C-reactive protein and only 8% of them delivered preterm. Differences were statistically highly significant. C-reactive protein can be used as a biomarker in prediction of premature delivery when it is associated with premature uterine contractions. As well it can be used as a screening test to detect cases that are at risk of premature delivery.

  20. Risk factors for premature birth in French Guiana: the importance of reducing health inequalities.

    Science.gov (United States)

    Leneuve-Dorilas, Malika; Favre, Anne; Carles, Gabriel; Louis, Alphonse; Nacher, Mathieu

    2017-11-27

    French Guiana has the highest birth rate in South America. This French territory also has the highest premature birth rate and perinatal mortality rate of all French territories. The objective was to determine the premature birth rate and to identify the prevalence of risk factors of premature birth in French Guiana. A retrospective study of all births in French Guiana was conducted between January 2013 and December 2014 using the computerized registry compiling all live births over 22 weeks of gestation on the territory. During this period 12 983 live births were reported on the territory. 13.5% of newborns were born before 37 (1755/12 983). The study of the registry revealed that common sociodemographic risk factors of prematurity were present. In addition, past obstetrical history was also important: a scarred uterus increased the risk of prematurity adjusted odds ratio =1.4, 95%CI (1.2-1.6). Similarly, obstetrical surveillance, the absence of preparation for birth or of prenatal interview increased the risk of prematurity by 2.4 and 2.3, the excess fraction in the population was 69% and 72.2%, respectively. Known classical risk factors are important. In the present study excess fractions were calculated in order to prioritize interventions to reduce the prematurity rate.

  1. EXPRESSION AND SIGNIFICANCE OF ERK PROTEIN IN HUMAN BREAST CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    张秀梅; 李柏林; 宋敏; 宋继谒

    2004-01-01

    Objective: To investigate the expression of ERK and p-ERK protein in human breast cancer and their corresponding tissue, to assess the significance of ERK signal pathway in tumorigenesis and progression of breast carcinoma. Methods: 40 breast cancer cases were used in S-P immunohistochemistry technique and Western Blot study. Results: The expression of ERK1, ERK2, and p- ERK protein levels increased remarkably in breast cancer tissues in comparison to normal tissues (P<0.01). The expression was upregulated by 1.32-, 1.53-and 4.27-fold, respectively. The overexpressions of ERK1, ERK2, and p- ERK proteins were obviously correlated with clinical stage of breast cancer. Protein levels of ERK and p-ERK were higher in stage III patients than in stage I and stage II patients (P<0.05). These proteins were strongly related with axillary lymph node metastasis of breast cancer, but not correlated with histopathological type and status of ER and PR of breast cancer. Expression of ERK1, and ERK2, protein showed a positive linear correlation. Conclusion: ERK signal transduction pathway is a key factor during human breast tumorigenesis and breast cancer progression.

  2. Long-term neuroglobin expression of human astrocytes following brain trauma.

    Science.gov (United States)

    Chen, Xiameng; Liu, Yuan; Zhang, Lin; Zhu, Peng; Zhu, Haibiao; Yang, Yu; Guan, Peng

    2015-10-08

    Neuroglobin (Ngb), a 17 kDa monomeric protein, was initially described as a vertebrate oxygen-binding heme protein in 2000 and detected in metabolically active organs or cells, like the brain, peripheral nervous system as well as certain endocrine cells. A large array of initial experimental work reported that Ngb displayed a neuron restricted expression pattern in mammalian brains. However, growing evidence indicated astrocytes may also express Ngb under pathological conditions. To address the question whether human astrocytes express Ngb under traumatic insults, we investigated Ngb immuno-reactivity in post-mortem human brain tissues that died of acute, sub-acute and chronic brain trauma, respectively. We observed astrocytic Ngb expression in sub-acute and chronic traumatic brains rather than acute traumatic brains. Strikingly, the Ngb immuno-reactive astrocytes were still strongly detectable in groups that died 12 months after brain trauma. Our findings may imply an unexplored role of Ngb in astrocytes and the involved mechanisms were suggested to be further characterized. Also, therapeutic application of Ngb or Ngb-inducible chemical compounds in neuro-genesis or astrocytic scar forming can be expected. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. Human amniotic epithelial cell feeder layers maintain human iPS cell pluripotency via inhibited endogenous microRNA-145 and increased Sox2 expression

    International Nuclear Information System (INIS)

    Liu, Te; Cheng, Weiwei; Huang, Yongyi; Huang, Qin; Jiang, Lizhen; Guo, Lihe

    2012-01-01

    Currently, human induced pluripotent stem (iPS) cells were generated from patient or disease-specific sources and share the same key properties as embryonic stem cells. This makes them attractive for personalized medicine, drug screens or cellular therapy. Long-term cultivation and maintenance of normal iPS cells in an undifferentiated self-renewing state are a major challenge. Our previous studies have shown that human amniotic epithelial cells (HuAECs) could provide a good source of feeder cells for mouse and human embryonic stem cells, or spermatogonial stem cells, but the mechanism for this is unknown. Here, we examined the effect of endogenous microRNA-145 regulation on Sox2 expression in human iPS cells by HuAECs feeder cells regulation, and in turn on human iPS cells pluripotency. We found that human IPS cells transfected with a microRNA-145 mutant expressed Sox2 at high levels, allowing iPS to maintain a high level of AP activity in long-term culture and form teratomas in SCID mice. Expression of stem cell markers was increased in iPS transfected with the microRNA-145 mutant, compared with iPS was transfected with microRNA-145. Besides, the expression of Drosha proteins of the microRNA-processor complex, required for the generation of precursor pre-miRNA, was significantly increased in human iPS cells cultured on MEF but not on HuAECs. Taken together, these results suggest that endogenous Sox2 expression may be regulated by microRNA-145 in human iPS cells with HuAECs feeder cells, and Sox2 is a crucial component required for maintenance of them in an undifferentiated, proliferative state capable of self-renewal. Highlights: ► microRNA-145 inhibits Sox2 expression in human iPS cells. ► microRNA-145 suppresses the self-renewal and pluripotency of human iPS cells. ► HuAECs regulate expression of microRNA-145 and Sox2 in human iPS cells. ► HuAECs feeder layers maintain human iPS cells pluripotency. ► HuAECs negatively regulates the synthesis of

  4. Human amniotic epithelial cell feeder layers maintain human iPS cell pluripotency via inhibited endogenous microRNA-145 and increased Sox2 expression

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Te, E-mail: liute79@yahoo.com [School of Environmental Science and Engineering, Donghua University, Shanghai 201620 (China); Shanghai Geriatric Institute of Chinese Medicine, Shanghai 200031 (China); Cheng, Weiwei [International Peace Maternity and Child Health Hospital, Shanghai Jiaotong University, Shanghai 200030 (China); Huang, Yongyi [Laboratoire PROTEE, Batiment R, Universite du Sud Toulon-Var, 83957 LA GARDE Cedex (France); Huang, Qin; Jiang, Lizhen [Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China); Guo, Lihe, E-mail: liute79@yahoo.com [Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031 (China)

    2012-02-15

    Currently, human induced pluripotent stem (iPS) cells were generated from patient or disease-specific sources and share the same key properties as embryonic stem cells. This makes them attractive for personalized medicine, drug screens or cellular therapy. Long-term cultivation and maintenance of normal iPS cells in an undifferentiated self-renewing state are a major challenge. Our previous studies have shown that human amniotic epithelial cells (HuAECs) could provide a good source of feeder cells for mouse and human embryonic stem cells, or spermatogonial stem cells, but the mechanism for this is unknown. Here, we examined the effect of endogenous microRNA-145 regulation on Sox2 expression in human iPS cells by HuAECs feeder cells regulation, and in turn on human iPS cells pluripotency. We found that human IPS cells transfected with a microRNA-145 mutant expressed Sox2 at high levels, allowing iPS to maintain a high level of AP activity in long-term culture and form teratomas in SCID mice. Expression of stem cell markers was increased in iPS transfected with the microRNA-145 mutant, compared with iPS was transfected with microRNA-145. Besides, the expression of Drosha proteins of the microRNA-processor complex, required for the generation of precursor pre-miRNA, was significantly increased in human iPS cells cultured on MEF but not on HuAECs. Taken together, these results suggest that endogenous Sox2 expression may be regulated by microRNA-145 in human iPS cells with HuAECs feeder cells, and Sox2 is a crucial component required for maintenance of them in an undifferentiated, proliferative state capable of self-renewal. Highlights: Black-Right-Pointing-Pointer microRNA-145 inhibits Sox2 expression in human iPS cells. Black-Right-Pointing-Pointer microRNA-145 suppresses the self-renewal and pluripotency of human iPS cells. Black-Right-Pointing-Pointer HuAECs regulate expression of microRNA-145 and Sox2 in human iPS cells. Black-Right-Pointing-Pointer HuAECs feeder

  5. Premature ovarian failure and ovarian autoimmunity

    NARCIS (Netherlands)

    J.A. Schoemaker (Joop); H.A. Drexhage (Hemmo); A. Hoek (Annemieke)

    1997-01-01

    textabstractPremature ovarian failure (POF) is defined as a syndrome characterized by menopause before the age of 40 yr. The patients suffer from anovulation and hypoestrogenism. Approximately 1% of women will experience menopause before the age of 40 yr. POF is a

  6. Chorioamniotic membrane separation and preterm premature rupture of membranes complicating in utero myelomeningocele repair.

    Science.gov (United States)

    Soni, Shelly; Moldenhauer, Julie S; Spinner, Susan S; Rendon, Norma; Khalek, Nahla; Martinez-Poyer, Juan; Johnson, Mark P; Adzick, N Scott

    2016-05-01

    Since the results of the Management of Myelomeningocele Study were published, maternal-fetal surgery for the in utero treatment of spina bifida has become accepted as a standard of care alternative. Despite promise with fetal management of myelomeningocele repair, there are significant complications to consider. Chorioamniotic membrane separation and preterm premature rupture of membranes are known complications of invasive fetal procedures. Despite their relative frequency associated with fetal procedures, few data exist regarding risk factors that may be attributed to their occurrence or the natural history of pregnancies that are affected with chorionic membrane separation or preterm premature rupture of membranes related to the procedure. The objective of this study was to review chorioamniotic membrane separation and preterm premature rupture of membranes in a cohort of patients undergoing fetal management of myelomeningocele repair including identification of risk factors and outcomes. This was a retrospective review of patients undergoing fetal management of myelomeningocele repair and subsequent delivery from January 2011 through December 2013 at 1 institution. Patients were identified through the institutional fetal management of myelomeningocele repair database and chart review was performed. Perioperative factors and outcomes among patients with chorioamniotic membrane separation and preterm premature rupture of membranes were compared to those without. Risk factors associated with the development of chorioamniotic membrane separation and preterm premature rupture of membranes were determined. A total of 88 patients underwent fetal management of myelomeningocele repair and subsequently delivered during the study period. In all, 21 patients (23.9%) were diagnosed with chorioamniotic membrane separation by ultrasound and preterm premature rupture of membranes occurred in 27 (30.7%). Among the chorioamniotic membrane separation patients, 10 (47.6%) were

  7. Automated discovery of functional generality of human gene expression programs.

    Directory of Open Access Journals (Sweden)

    Georg K Gerber

    2007-08-01

    Full Text Available An important research problem in computational biology is the identification of expression programs, sets of co-expressed genes orchestrating normal or pathological processes, and the characterization of the functional breadth of these programs. The use of human expression data compendia for discovery of such programs presents several challenges including cellular inhomogeneity within samples, genetic and environmental variation across samples, uncertainty in the numbers of programs and sample populations, and temporal behavior. We developed GeneProgram, a new unsupervised computational framework based on Hierarchical Dirichlet Processes that addresses each of the above challenges. GeneProgram uses expression data to simultaneously organize tissues into groups and genes into overlapping programs with consistent temporal behavior, to produce maps of expression programs, which are sorted by generality scores that exploit the automatically learned groupings. Using synthetic and real gene expression data, we showed that GeneProgram outperformed several popular expression analysis methods. We applied GeneProgram to a compendium of 62 short time-series gene expression datasets exploring the responses of human cells to infectious agents and immune-modulating molecules. GeneProgram produced a map of 104 expression programs, a substantial number of which were significantly enriched for genes involved in key signaling pathways and/or bound by NF-kappaB transcription factors in genome-wide experiments. Further, GeneProgram discovered expression programs that appear to implicate surprising signaling pathways or receptor types in the response to infection, including Wnt signaling and neurotransmitter receptors. We believe the discovered map of expression programs involved in the response to infection will be useful for guiding future biological experiments; genes from programs with low generality scores might serve as new drug targets that exhibit minimal

  8. Metabolomics of prematurity: analysis of patterns of amino acids, enzymes, and endocrine markers by categories of gestational age.

    Science.gov (United States)

    Wilson, Kumanan; Hawken, Steven; Ducharme, Robin; Potter, Beth K; Little, Julian; Thébaud, Bernard; Chakraborty, Pranesh

    2014-02-01

    Prematurity may influence the levels of amino acids, enzymes, and endocrine markers obtained through newborn screening. Identifying which analytes are the most affected by degree of prematurity could provide insight into how prematurity impacts metabolism. Analytes from blood spots assayed by Newborn Screening Ontario between March 2006 and April 2009 were used in this analysis. We examined the associations between the degree of prematurity and the levels of amino acids, enzymes, and endocrine markers in all newborns with and without adjustment for birth weight, feeding status, sample timing, transfusion, and sex. Our analysis included the following cohorts: 373,819 children born at term (>36 wk gestation), 26,483 near-term children (33-36 wk gestation), 4,354 very premature children (28-32 wk gestation), and 1,146 extremely premature children (prematurity, the levels of three amino acids (arginine, leucine, and valine) were at least 50% different between the cohorts of extremely premature and term children. The levels of 17-hydroxyprogesterone increased with increasing prematurity, while thyrotropin-stimulating hormone values consistently decreased with increasing prematurity. None of the three enzyme markers we examined showed a trend in levels across categories of prematurity. This study demonstrates that children at different stages of prematurity are metabolically distinct. Future research should focus on the mechanism by which specific analytes are influenced by prematurity.

  9. Human glioblastoma-associated microglia/monocytes express a distinct RNA profile compared to human control and murine samples.

    Science.gov (United States)

    Szulzewsky, Frank; Arora, Sonali; de Witte, Lot; Ulas, Thomas; Markovic, Darko; Schultze, Joachim L; Holland, Eric C; Synowitz, Michael; Wolf, Susanne A; Kettenmann, Helmut

    2016-08-01

    Glioblastoma (GBM) is the most aggressive brain tumor in adults. It is strongly infiltrated by microglia and peripheral monocytes that support tumor growth. In the present study we used RNA sequencing to compare the expression profile of CD11b(+) human glioblastoma-associated microglia/monocytes (hGAMs) to CD11b(+) microglia isolated from non-tumor samples. Hierarchical clustering and principal component analysis showed a clear separation of the two sample groups and we identified 334 significantly regulated genes in hGAMs. In comparison to human control microglia hGAMs upregulated genes associated with mitotic cell cycle, cell migration, cell adhesion, and extracellular matrix organization. We validated the expression of several genes associated with extracellular matrix organization in samples of human control microglia, hGAMs, and the hGAMs-depleted fraction via qPCR. The comparison to murine GAMs (mGAMs) showed that both cell populations share a significant fraction of upregulated transcripts compared with their respective controls. These genes were mostly related to mitotic cell cycle. However, in contrast to murine cells, human GAMs did not upregulate genes associated to immune activation. Comparison of human and murine GAMs expression data to several data sets of in vitro-activated human macrophages and murine microglia showed that, in contrast to mGAMs, hGAMs share a smaller overlap to these data sets in general and in particular to cells activated by proinflammatory stimulation with LPS + INFγ or TNFα. Our findings provide new insights into the biology of human glioblastoma-associated microglia/monocytes and give detailed information about the validity of murine experimental models. GLIA 2016 GLIA 2016;64:1416-1436. © 2016 Wiley Periodicals, Inc.

  10. Prematurity and fetal lung response after tracheal occlusion in fetuses with severe congenital diaphragmatic hernia.

    Science.gov (United States)

    Sananes, Nicolas; Rodo, Carlota; Peiro, Jose Luis; Britto, Ingrid Schwach Werneck; Sangi-Haghpeykar, Haleh; Favre, Romain; Joal, Arnaud; Gaudineau, Adrien; Silva, Marcos Marques da; Tannuri, Uenis; Zugaib, Marcelo; Carreras, Elena; Ruano, Rodrigo

    2016-09-01

    To evaluate the independent association of fetal pulmonary response and prematurity to postnatal outcomes after fetal tracheal occlusion for congenital diaphragmatic hernia. Fetal pulmonary response, prematurity (prematurity (prematurity was not statistically associated with mortality after controlling for fetal pulmonary response (aOR 0.52, 95% CI 0.12-2.30, p=0.367). Fetal pulmonary response after FETO is the most important factor associated with survival, independently from the gestational age at delivery.

  11. DENGUE DURING PREGNANCY: ASSOCIATION WITH LOW BIRTH WEIGHT AND PREMATURITY

    Directory of Open Access Journals (Sweden)

    Christiane Fernandes RIBEIRO

    2016-01-01

    Full Text Available The aim of this study was to evaluate the effects of dengue virus infection during pregnancy and its correlation with low birth weight, prematurity, and asphyxia. A non-concurrent cohort study reveals the association of dengue during pregnancy with prematurity and low birth weight, when birth occurred during the maternal-fetal viremia period (p = 0.016 and p < 0.0001, respectively.

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

    Science.gov (United States)

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

    2009-08-11

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

  13. Genome scan identifies a locus affecting gamma-globin expression in human beta-cluster YAC transgenic mice

    Energy Technology Data Exchange (ETDEWEB)

    Lin, S.D.; Cooper, P.; Fung, J.; Weier, H.U.G.; Rubin, E.M.

    2000-03-01

    Genetic factors affecting post-natal g-globin expression - a major modifier of the severity of both b-thalassemia and sickle cell anemia, have been difficult to study. This is especially so in mice, an organism lacking a globin gene with an expression pattern equivalent to that of human g-globin. To model the human b-cluster in mice, with the goal of screening for loci affecting human g-globin expression in vivo, we introduced a human b-globin cluster YAC transgene into the genome of FVB mice . The b-cluster contained a Greek hereditary persistence of fetal hemoglobin (HPFH) g allele resulting in postnatal expression of human g-globin in transgenic mice. The level of human g-globin for various F1 hybrids derived from crosses between the FVB transgenics and other inbred mouse strains was assessed. The g-globin level of the C3HeB/FVB transgenic mice was noted to be significantly elevated. To map genes affecting postnatal g-globin expression, a 20 centiMorgan (cM) genome scan of a C3HeB/F VB transgenics [prime] FVB backcross was performed, followed by high-resolution marker analysis of promising loci. From this analysis we mapped a locus within a 2.2 cM interval of mouse chromosome 1 at a LOD score of 4.2 that contributes 10.4% of variation in g-globin expression level. Combining transgenic modeling of the human b-globin gene cluster with quantitative trait analysis, we have identified and mapped a murine locus that impacts on human g-globin expression in vivo.

  14. Long-term high-level expression of human beta-globin occurs following transplantation of transgenic marrow into irradiated mice.

    Science.gov (United States)

    Himelstein, A; Ward, M; Podda, S; de la Flor Weiss, E; Costantini, F; Bank, A

    1993-03-01

    When the human beta-globin gene is transferred into the bone marrow cells of live mice, its expression is very low. To investigate the reason for this, we transferred the bone marrow of transgenic mice containing and expressing the human beta-globin into irradiated recipients. We demonstrate that long-term high level expression of the human beta-globin gene can be maintained in the marrow and blood of irradiated recipients following transplantation. Although expression decreased over time in most animals because of host marrow reconstitution, the ratio of human beta-globin transgene expression to endogenous mouse beta-globin gene expression in donor-derived erythroid cells remained constant over time. We conclude that there is no inherent limitation to efficient expression of an exogenous human beta-globin gene in mouse bone marrow cells following marrow transplantation.

  15. Expression of delta-catenin is associated with progression of human astrocytoma

    International Nuclear Information System (INIS)

    MingHao, Wang; Qianze, Dong; Di, Zhang; YunJie, Wang

    2011-01-01

    δ-Catenin (CTNND2), which encodes a scaffold protein in humans, has been found in a few malignancies. However, the expression pattern and contribution of δ-catenin to astrocytoma progression are unclear. We investigated δ-catenin expression in human astrocytoma samples and its function in astrocytoma cell lines using immunohistochemistry, siRNA knockdown, transfection, MTT, transwell migration and Rac1 pulldown techniques. δ-Catenin protein expression was detected in cytoplasm of astrocytoma cells by immunohistochemistry. Analysis showed that grade I astrocytoma (0%, 0/11) and glial cells from normal brain tissue exhibited negative staining. δ-Catenin expression was significantly higher in grade III-IV (35%, 29/84) compared to grade II astrocytoma cells (18%, 11/61); p < 0.01). In addition, CTNND2 overexpression promoted proliferation, invasion and Rac1 activity of U251 astrocytoma cells. Treatment of δ-catenin-transfected cells with a Rac1 inhibitor decreased Rac1 activity and invasion. δ-Catenin knockdown in U87 glioblastoma cell decreased cell proliferation, invasion and Rac1 activity. The results suggest that δ-catenin expression is associated with the malignant progression of astrocytoma and promotes astrocytoma cell invasion through upregulation of Rac1 activity. δ-Catenin expression levels may serve as a useful marker of the biological behavior of astrocytoma cells

  16. Epidermal growth factor increases LRF/Pokemon expression in human prostate cancer cells.

    Science.gov (United States)

    Aggarwal, Himanshu; Aggarwal, Anshu; Agrawal, Devendra K

    2011-10-01

    Leukemia/lymphoma related factor/POK erythroid myeloid ontogenic factor (LRF/Pokemon) is a member of the POK family of proteins that promotes oncogenesis in several forms of cancer. Recently, we found higher LRF expression in human breast and prostate carcinomas compared to the corresponding normal tissues. The aim of this study was to examine the regulation of LRF expression in human prostate cells. Epidermal growth factor (EGF) and its receptors mediate several tumorigenic cascades that regulate cell differentiation, proliferation, migration and survival of prostate cancer cells. There was significantly higher level of LRF expression in the nucleus of LNCaP and PC-3 cells than RWPE-1 cells. A significant increase in LRF expression was observed with increasing doses of EGF in more aggressive and androgen-sensitive prostate cancer cells suggesting that EGF signaling pathway is critical in upregulating the expression of LRF/Pokemon to promote oncogenesis. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. [Ketoconazole and clindamycin efficacy vs oral clindamycin in premature membranes rupture prevention].

    Science.gov (United States)

    Castillo Huerta, Eugenio; Garibay Valencia, Miguel; Mirabent-González, Felio

    2008-07-01

    Vulvovaginitis is one of the main causes of premature membrane rupture. To evaluate effectiveness of a combination of ketoconazole (400 mg) and clindamycin (100 mg) in vaginal tablets, compared with clindamicyn alone (600 mg/daily) orally, for six days, to prevent premature membrane rupture in patients with vulvovaginitis. Longitudinal, prospective, comparative, randomized, double-blind, double-dummy study in patients older than 18 years, during them third trimester of normoevolutive pregnancy with symptomatic vulvovaginitis. Patients were monitored as out patient. Genital secretion culture and fresh studies were made. Signs and symptoms were evaluated in regular intervals: 4, 7 and 11 days. Pregnancy control was performed every three weeks, until childbirth or premature membrane rupture. 105 patients were included: 53 in the group of ketoconazole and clindamicyn (1), and 52 in the group of clindamycin alone (2). Symptoms were similar in both groups of treatment, without statistically significant differences. A case of group 2 has premature membrane rupture (p = 0.495). C. albicans was cultured in 35% of group 2 and in 11% of group 2. No adverse events with treatments were reported. The combination of ketoconazole and cindamycin was effective to prevent premature membrane rupture in patients with vulvovaginitis.

  18. Inorganic arsenic represses interleukin-17A expression in human activated Th17 lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Morzadec, Claudie; Macoch, Mélinda; Robineau, Marc; Sparfel, Lydie [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 avenue du Professeur Léon Bernard, 35043 Rennes (France); Fardel, Olivier [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 avenue du Professeur Léon Bernard, 35043 Rennes (France); Pôle Biologie, Centre Hospitalier Universitaire (CHU) Rennes, 2 rue Henri Le Guilloux, 35033 Rennes (France); Vernhet, Laurent, E-mail: laurent.vernhet@univ-rennes1.fr [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 avenue du Professeur Léon Bernard, 35043 Rennes (France)

    2012-08-01

    Trivalent inorganic arsenic [As(III)] is an efficient anticancer agent used to treat patients suffering from acute promyelocytic leukemia. Recently, experimental studies have clearly demonstrated that this metalloid can also cure lymphoproliferative and/or pro-inflammatory syndromes in different murine models of chronic immune-mediated diseases. T helper (Th) 1 and Th17 lymphocytes play a central role in development of these diseases, in mice and humans, especially by secreting the potent pro-inflammatory cytokine interferon-γ and IL-17A, respectively. As(III) impairs basic functions of human T cells but its ability to modulate secretion of pro-inflammatory cytokines by differentiated Th lymphocytes is unknown. In the present study, we demonstrate that As(III), used at concentrations clinically achievable in plasma of patients, has no effect on the secretion of interferon-γ from Th1 cells but almost totally blocks the expression and the release of IL-17A from human Th17 lymphocytes co-stimulated for five days with anti-CD3 and anti-CD28 antibodies, in the presence of differentiating cytokines. In addition, As(III) specifically reduces mRNA levels of the retinoic-related orphan receptor (ROR)C gene which encodes RORγt, a key transcription factor controlling optimal IL-17 expression in fully differentiated Th17 cells. The metalloid also blocks initial expression of IL-17 gene induced by the co-stimulation, probably in part by impairing activation of the JNK/c-Jun pathway. In conclusion, our results demonstrate that As(III) represses expression of the major pro-inflammatory cytokine IL-17A produced by human Th17 lymphocytes, thus strengthening the idea that As(III) may be useful to treat inflammatory immune-mediated diseases in humans. -- Highlights: ► Arsenic inhibits secretion of IL-17A from human naïve and memory Th17 lymphocytes. ► Arsenic represses early expression of IL-17A gene in human activated T lymphocytes. ► Arsenic interferes with activation of

  19. Retinopathy of prematurity: a review of risk factors and their clinical significance.

    Science.gov (United States)

    Kim, Sang Jin; Port, Alexander D; Swan, Ryan; Campbell, J Peter; Chan, R V Paul; Chiang, Michael F

    2018-04-19

    Retinopathy of prematurity (ROP) is a retinal vasoproliferative disease that affects premature infants. Despite improvements in neonatal care and management guidelines, ROP remains a leading cause of childhood blindness worldwide. Current screening guidelines are primarily based on two risk factors: birth weight and gestational age; however, many investigators have suggested other risk factors, including maternal factors, prenatal and perinatal factors, demographics, medical interventions, comorbidities of prematurity, nutrition, and genetic factors. We review the existing literature addressing various possible ROP risk factors. Although there have been contradictory reports, and the risk may vary between different populations, understanding ROP risk factors is essential to develop predictive models, to gain insights into pathophysiology of retinal vascular diseases and diseases of prematurity, and to determine future directions in management of and research in ROP. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. Human sex hormone-binding globulin gene expression- multiple promoters and complex alternative splicing

    Directory of Open Access Journals (Sweden)

    Rosner William

    2009-05-01

    Full Text Available Abstract Background Human sex hormone-binding globulin (SHBG regulates free sex steroid concentrations in plasma and modulates rapid, membrane based steroid signaling. SHBG is encoded by an eight exon-long transcript whose expression is regulated by a downstream promoter (PL. The SHBG gene was previously shown to express a second major transcript of unknown function, derived from an upstream promoter (PT, and two minor transcripts. Results We report that transcriptional expression of the human SHBG gene is far more complex than previously described. PL and PT direct the expression of at least six independent transcripts each, resulting from alternative splicing of exons 4, 5, 6, and/or 7. We mapped two transcriptional start sites downstream of PL and PT, and present evidence for a third SHBG gene promoter (PN within the neighboring FXR2 gene; PN regulates the expression of at least seven independent SHBG gene transcripts, each possessing a novel, 164-nt first exon (1N. Transcriptional expression patterns were generated for human prostate, breast, testis, liver, and brain, and the LNCaP, MCF-7, and HepG2 cell lines. Each expresses the SHBG transcript, albeit in varying abundance. Alternative splicing was more pronounced in the cancer cell lines. PL- PT- and PN-derived transcripts were most abundant in liver, testis, and prostate, respectively. Initial findings reveal the existence of a smaller immunoreactive SHBG species in LNCaP, MCF-7, and HepG2 cells. Conclusion These results extend our understanding of human SHBG gene transcription, and raise new and important questions regarding the role of novel alternatively spliced transcripts, their function in hormonally responsive tissues including the breast and prostate, and the role that aberrant SHBG gene expression may play in cancer.

  1. How best to capture the respiratory consequences of prematurity?

    Science.gov (United States)

    Ciuffini, Francesca; Robertson, Colin F; Tingay, David G

    2018-03-31

    Chronic respiratory morbidity is a common complication of premature birth, generally defined by the presence of bronchopulmonary dysplasia, both clinically and in trials of respiratory therapies. However, recent data have highlighted that bronchopulmonary dysplasia does not correlate with chronic respiratory morbidity in older children born preterm. Longitudinally evaluating pulmonary morbidity from early life through to childhood provides a more rational method of defining the continuum of chronic respiratory morbidity of prematurity, and offers new insights into the efficacy of neonatal respiratory interventions. The changing nature of preterm lung disease suggests that a multimodal approach using dynamic lung function assessment will be needed to assess the efficacy of a neonatal respiratory therapy and predict the long-term respiratory consequences of premature birth. Our aim is to review the literature regarding the long-term respiratory outcomes of neonatal respiratory strategies, the difficulties of assessing dynamic lung function in infants, and potential new solutions. Copyright ©ERS 2018.

  2. Temporal expression pattern of genes during the period of sex differentiation in human embryonic gonads

    DEFF Research Database (Denmark)

    Mamsen, Linn S; Ernst, Emil H; Borup, Rehannah

    2017-01-01

    The precise timing and sequence of changes in expression of key genes and proteins during human sex-differentiation and onset of steroidogenesis was evaluated by whole-genome expression in 67 first trimester human embryonic and fetal ovaries and testis and confirmed by qPCR and immunohistochemistry...... (IHC). SRY/SOX9 expression initiated in testis around day 40 pc, followed by initiation of AMH and steroidogenic genes required for androgen production at day 53 pc. In ovaries, gene expression of RSPO1, LIN28, FOXL2, WNT2B, and ETV5, were significantly higher than in testis, whereas GLI1...... was significantly higher in testis than ovaries. Gene expression was confirmed by IHC for GAGE, SOX9, AMH, CYP17A1, LIN28, WNT2B, ETV5 and GLI1. Gene expression was not associated with the maternal smoking habits. Collectively, a precise temporal determination of changes in expression of key genes involved in human...

  3. Premature chromosome condensation studies in human leukemia. I. Pretreatment characteristics.

    Science.gov (United States)

    Hittelman, W N; Broussard, L C; McCredie, K

    1979-11-01

    The phenomenon of premature chromosome condensation (PCC) was used to compare the bone marrow proliferation characteristics of 163 patients with various forms of leukemia prior to the initiation of new therapy. The proliferative potential index (PPI, or fraction of G1 cells in late G1 phase) and the fraction of cells in S phase was determined and compared to the type of disease and the bone marrow blast infiltrate for each patient. Previously untreated patients with acute leukemia exhibited an average PPI value three times that of normal bone marrow (37.5% for acute myeloblastic leukemia [AML], acute monomyeloblastic leukemia [AMML], or acute promyelocytic leukemia [APML] and 42% for acute lymphocytic leukemia [ALL] or acute undifferentiated leukemia [AUL]). Untreated chronic myelogenous leukemia (CML) patients showed intermediate PPI values (25.2%), whereas CML patients with controlled disease exhibited nearly normal PPI values (14.6%). On the other hand, blastic-phase CML patients exhibited PPI values closer to that observed in patients with acute leukemia (35.4%). Seven patients with chronic lymphocytic leukemia (CLL) exhibited even higher PPI values. No correlations were observed between PPI values, fraction of cells in S phase, and marrow blast infiltrate. For untreated acute disease patients, PPI values were prognostic for response only at low and high PPI values. These results suggest that the PCC-determined proliferative potential is a biologic reflection of the degree of malignancy within the bone marrow.

  4. Osteopenia (metabolic bone disease) of prematurity

    Science.gov (United States)

    Osteopenia is defined as postnatal bone mineralization that is inadequate to fully mineralize bones. Osteopenia occurs commonly in very low birth weight (VLBW) infants. Prior to the use of high-mineral containing diets for premature infants, which is the current practice, significant radiographic ch...

  5. Multimedia Content Development as a Facial Expression Datasets for Recognition of Human Emotions

    Science.gov (United States)

    Mamonto, N. E.; Maulana, H.; Liliana, D. Y.; Basaruddin, T.

    2018-02-01

    Datasets that have been developed before contain facial expression from foreign people. The development of multimedia content aims to answer the problems experienced by the research team and other researchers who will conduct similar research. The method used in the development of multimedia content as facial expression datasets for human emotion recognition is the Villamil-Molina version of the multimedia development method. Multimedia content developed with 10 subjects or talents with each talent performing 3 shots with each capturing talent having to demonstrate 19 facial expressions. After the process of editing and rendering, tests are carried out with the conclusion that the multimedia content can be used as a facial expression dataset for recognition of human emotions.

  6. Cholesterol can modulate mitochondrial aquaporin-8 expression in human hepatic cells.

    Science.gov (United States)

    Danielli, Mauro; Capiglioni, Alejo M; Marrone, Julieta; Calamita, Giuseppe; Marinelli, Raúl A

    2017-05-01

    Hepatocyte mitochondrial aquaporin-8 (mtAQP8) works as a multifunctional membrane channel protein that facilitates the uptake of ammonia for its detoxification to urea as well as the mitochondrial release of hydrogen peroxide. Since early oligonucleotide microarray studies in liver of cholesterol-fed mice showed an AQP8 downregulation, we tested whether alterations of cholesterol content per se modulate mtAQP8 expression in human hepatocyte-derived Huh-7 cells. Cholesterol loading with methyl-β-cyclodextrin (mβCD):cholesterol complexes downregulated the proteolytic activation of cholesterol-responsive sterol regulatory element-binding protein (SREBP) transcriptions factors 1 and 2, and the expression of the target gene 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR). Under such conditions, mtAQP8 mRNA and protein expressions were significantly reduced. In contrast, cholesterol depletion using mβCD alone increased SREBP-1 and 2 activation and upregulated HMGCR and mtAQP8 mRNA and protein expressions. The results suggest that cholesterol can regulate transcriptionally human hepatocyte mtAQP8 expression likely via SREBPs. The functional implications of our findings are discussed. © 2017 IUBMB Life, 69(5):341-346, 2017. © 2017 International Union of Biochemistry and Molecular Biology.

  7. Expression of the human multidrug transporter in insect cells by a recombinant baculovirus

    International Nuclear Information System (INIS)

    Germann, U.A.; Willingham, M.C.; Pastan, I.; Gottesman, M.M.

    1990-01-01

    The plasma membrane associated human multidrug resistance (MDR1) gene product, known as the 170-kDa P-glycoprotein or the multidrug transporter, acts as an ATP-dependent efflux pump for various cytotoxic agents. The authors expressed recombinant human multidrug transporter in a baculovirus expression system to obtain large quantities and further investigate its structure and mechanism of action. MDR1 cDNA was inserted into the genome of the Autographa californica nuclear polyhedrosis virus under the control of the polyhedrin promoter. Spodoptera frugiperda insect cells synthesized high levels of recombinant multidrug transporter 2-3 days after infection. The transporter was localized by immunocytochemical methods on the external surface of the plasma membranes, in the Golgi apparatus, and within the nuclear envelope. The human multidrug transporter expressed in insect cells is not susceptible to endoglycosidase F treatment and has a lower apparent molecular weight of 140,000, corresponding to the nonglycosylated precursor of its authentic counterpart expressed in multidrug-resistant cells. Labeling experiments showed that the recombinant multidrug transporter is phosphorylated and can be photoaffinity labeled by [ 3 H]azidopine, presumably at the same two sites as the native protein. Various drugs and reversing agents compete with the [ 3 H]azidopine binding reaction when added in excess, indicating that the recombinant human multidrug transporter expressed in insect cells is functionally similar to its authentic counterpart

  8. Genetic Variants Contribute to Gene Expression Variability in Humans

    Science.gov (United States)

    Hulse, Amanda M.; Cai, James J.

    2013-01-01

    Expression quantitative trait loci (eQTL) studies have established convincing relationships between genetic variants and gene expression. Most of these studies focused on the mean of gene expression level, but not the variance of gene expression level (i.e., gene expression variability). In the present study, we systematically explore genome-wide association between genetic variants and gene expression variability in humans. We adapt the double generalized linear model (dglm) to simultaneously fit the means and the variances of gene expression among the three possible genotypes of a biallelic SNP. The genomic loci showing significant association between the variances of gene expression and the genotypes are termed expression variability QTL (evQTL). Using a data set of gene expression in lymphoblastoid cell lines (LCLs) derived from 210 HapMap individuals, we identify cis-acting evQTL involving 218 distinct genes, among which 8 genes, ADCY1, CTNNA2, DAAM2, FERMT2, IL6, PLOD2, SNX7, and TNFRSF11B, are cross-validated using an extra expression data set of the same LCLs. We also identify ∼300 trans-acting evQTL between >13,000 common SNPs and 500 randomly selected representative genes. We employ two distinct scenarios, emphasizing single-SNP and multiple-SNP effects on expression variability, to explain the formation of evQTL. We argue that detecting evQTL may represent a novel method for effectively screening for genetic interactions, especially when the multiple-SNP influence on expression variability is implied. The implication of our results for revealing genetic mechanisms of gene expression variability is discussed. PMID:23150607

  9. Regulation of MYCN expression in human neuroblastoma cells

    International Nuclear Information System (INIS)

    Jacobs, Joannes FM; Bokhoven, Hans van; Leeuwen, Frank N van; Hulsbergen-van de Kaa, Christina A; Vries, I Jolanda M de; Adema, Gosse J; Hoogerbrugge, Peter M; Brouwer, Arjan PM de

    2009-01-01

    Amplification of the MYCN gene in neuroblastoma (NB) is associated with a poor prognosis. However, MYCN-amplification does not automatically result in higher expression of MYCN in children with NB. We hypothesized that the discrepancy between MYCN gene expression and prognosis in these children might be explained by the expression of either MYCN-opposite strand (MYCNOS) or the shortened MYCN-isoform (ΔMYCN) that was recently identified in fetal tissues. Both MYCNOS and ΔMYCN are potential inhibitors of MYCN either at the mRNA or at the protein level. Expression of MYCN, MYCNOS and ΔMYCN was measured in human NB tissues of different stages. Transcript levels were quantified using a real-time reverse transcriptase polymerase chain reaction assay (QPCR). In addition, relative expression of these three transcripts was compared to the number of MYCN copies, which was determined by genomic real-time PCR (gQPCR). Both ΔMYCN and MYCNOS are expressed in all NBs examined. In NBs with MYCN-amplification, these transcripts are significantly higher expressed. The ratio of MYCN:ΔMYCN expression was identical in all tested NBs. This indicates that ΔMYCN and MYCN are co-regulated, which suggests that ΔMYCN is not a regulator of MYCN in NB. However, the ratio of MYCNOS:MYCN expression is directly correlated with NB disease stage (p = 0.007). In the more advanced NB stages and NBs with MYCN-amplification, relatively more MYCNOS is present as compared to MYCN. Expression of the antisense gene MYCNOS might be relevant to the progression of NB, potentially by directly inhibiting MYCN transcription by transcriptional interference at the DNA level. The MYCNOS:MYCN-ratio in NBs is significantly correlated with both MYCN-amplification and NB-stage. Our data indicate that in NB, MYCN expression levels might be influenced by MYCNOS but not by ΔMYCN

  10. Cigarette smoking decreases global microRNA expression in human alveolar macrophages.

    Directory of Open Access Journals (Sweden)

    Joel W Graff

    Full Text Available Human alveolar macrophages are critical components of the innate immune system. Cigarette smoking-induced changes in alveolar macrophage gene expression are linked to reduced resistance to pulmonary infections and to the development of emphysema/COPD. We hypothesized that microRNAs (miRNAs could control, in part, the unique messenger RNA (mRNA expression profiles found in alveolar macrophages of cigarette smokers. Activation of macrophages with different stimuli in vitro leads to a diverse range of M1 (inflammatory and M2 (anti-inflammatory polarized phenotypes that are thought to mimic activated macrophages in distinct tissue environments. Microarray mRNA data indicated that smoking promoted an "inverse" M1 mRNA expression program, defined by decreased expression of M1-induced transcripts and increased expression of M1-repressed transcripts with few changes in M2-regulated transcripts. RT-PCR arrays identified altered expression of many miRNAs in alveolar macrophages of smokers and a decrease in global miRNA abundance. Stratification of human subjects suggested that the magnitude of the global decrease in miRNA abundance was associated with smoking history. We found that many of the miRNAs with reduced expression in alveolar macrophages of smokers were predicted to target mRNAs upregulated in alveolar macrophages of smokers. For example, miR-452 is predicted to target the transcript encoding MMP12, an important effector of smoking-related diseases. Experimental antagonism of miR-452 in differentiated monocytic cells resulted in increased expression of MMP12. The comprehensive mRNA and miRNA expression profiles described here provide insight into gene expression regulation that may underlie the adverse effects cigarette smoking has on alveolar macrophages.

  11. Expression of biologically active human interferon alpha 2 in aloe vera

    Science.gov (United States)

    We have developed a system for transgenic expression of proteins in Aloe Vera. Using this approach we have generated plants expressing the human gene interferon alpha 2, IFNa2. IFNa2 is a small secreted cytokine that plays a vital role in regulating the body’s immune response to viral infections a...

  12. LncRNA Expression Profile of Human Thoracic Aortic Dissection by High-Throughput Sequencing.

    Science.gov (United States)

    Sun, Jie; Chen, Guojun; Jing, Yuanwen; He, Xiang; Dong, Jianting; Zheng, Junmeng; Zou, Meisheng; Li, Hairui; Wang, Shifei; Sun, Yili; Liao, Wangjun; Liao, Yulin; Feng, Li; Bin, Jianping

    2018-01-01

    In this study, the long non-coding RNA (lncRNA) expression profile in human thoracic aortic dissection (TAD), a highly lethal cardiovascular disease, was investigated. Human TAD (n=3) and normal aortic tissues (NA) (n=3) were examined by high-throughput sequencing. Bioinformatics analyses were performed to predict the roles of aberrantly expressed lncRNAs. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to validate the results. A total of 269 lncRNAs (159 up-regulated and 110 down-regulated) and 2, 255 mRNAs (1 294 up-regulated and 961 down-regulated) were aberrantly expressed in human TAD (fold-change> 1.5, PTAD than in NA. The predicted binding motifs of three up-regulated lncRNAs (ENSG00000248508, ENSG00000226530, and EG00000259719) were correlated with up-regulated RUNX1 (R=0.982, PTAD. These findings suggest that lncRNAs are novel potential therapeutic targets for human TAD. © 2018 The Author(s). Published by S. Karger AG, Basel.

  13. Anemia of prematurity: time for a change in transfusion management?

    OpenAIRE

    Khodabux, Chantal Muriel

    2013-01-01

    In this thesis we investigated clinical effects of allogeneic red blood cell (RBC) transfusions in premature infants, different transfusion volumes in relation to neonatal outcome in premature infants and the use of autologous cord blood (CB) as an alternative for allogeneic transfusions. Despite the use of a national transfusion guideline, we observed significant differences concerning the total amount of administered transfusions. A liberal transfusion strategy and a higher transfusion volu...

  14. The relationship between pregnancy, preterm and premature delivery

    Directory of Open Access Journals (Sweden)

    Soleymani-e- Shayesteh Y

    2002-06-01

    Full Text Available During pregnancy, different froms of periodontal disease such as pregnancy gingivitis, pregnancy tumors, pregnancy stomatitis, may be encountered. But the most considerable point is the pregnant women's infection with periodontal disease and its effect on delivery and weight of newborn infants. Based on the latest researches and statistics, it is concluded that periodontal disease is an important risk factor, leading to preterm or premature delivery. On the other hand, poor hygiene, should be considered as another danger, resulting in premature delivery. Besides, the presence of a collection of oral fosobacteria in ammoniutic fluid in mothers with premature delivery, increases the probability of an oral- haematogenous connection. Moreover, prostaglandin E2, in cervicular fluid, has been considered as an index for periodontal disease activity and loss of weight at the time of birth. These findings suggest that effective steps, to prevent preterm delivery, can be taken, if women, genycologists and dentists have enough knowledge. This article focuses on the special supervision that is required to prevent the effects of hormonal changes on periodontal tissues and conversely to reduce systemic disorders resulting from periodontal disease, in pregnant woman.

  15. MicroRNA Expression Profiles in Cultured Human Fibroblasts in Space

    Science.gov (United States)

    Wu, Honglu; Lu, Tao; Jeevarajan, John; Rohde, Larry; Zhang, Ye

    2014-01-01

    Microgravity, or an altered gravity environment from the static 1g, has been shown to influence global gene expression patterns and protein levels in living organisms. However, it is unclear how these changes in gene and protein expressions are related to each other or are related to other factors regulating such changes. A different class of RNA, the small non-coding microRNA (miRNA), can have a broad effect on gene expression networks by mainly inhibiting the translation process. Previously, we investigated changes in the expression of miRNA and related genes under simulated microgravity conditions on the ground using the NASA invented bioreactor. In comparison to static 1 g, simulated microgravity altered a number of miRNAs in human lymphoblastoid cells. Pathway analysis with the altered miRNAs and RNA expressions revealed differential involvement of cell communication and catalytic activity, as well as immune response signaling and NGF activation of NF-kB pathways under simulated microgravity condition. The network analysis also identified several projected networks with c- Rel, ETS1 and Ubiquitin C as key factors. In a flight experiment on the International Space Station (ISS), we will investigate the effects of actual spaceflight on miRNA expressions in nondividing human fibroblast cells in mostly G1 phase of the cell cycle. A fibroblast is a type of cell that synthesizes the extracellular matrix and collagen, the structural framework for tissues, and plays a critical role in wound healing and other functions. In addition to miRNA expressions, we will investigate the effects of spaceflight on the cellular response to DNA damages from bleomycin treatment.

  16. Gene expression profiles in adenosine-treated human mast cells ...

    African Journals Online (AJOL)

    Gene expression profiles in adenosine-treated human mast cells. ... SW Kang, JE Jeong, CH Kim, SH Choi, SH Chae, SA Jun, HJ Cha, JH Kim, YM Lee, YS ... beta 4, ring finger protein, high-mobility group, calmodulin 2, RAN binding protein, ...

  17. Complications of Prematurity - An Infographic

    Science.gov (United States)

    Chandrasekharan, Praveen; Rawat, Munmun; Lakshminrusimha, Satyan

    2017-01-01

    Infographics or information graphics are easy-to-understand visual representation of knowledge. An infographic outlining the course of an extremely preterm infant and various potential complications encountered during a neonatal intensive care unit (NICU) stay was developed. This infographic can be used to discuss outcomes of prematurity during prenatal counseling and while the infant is in the NICU. PMID:29138522

  18. Serial analysis of gene expression (SAGE) in normal human trabecular meshwork.

    Science.gov (United States)

    Liu, Yutao; Munro, Drew; Layfield, David; Dellinger, Andrew; Walter, Jeffrey; Peterson, Katherine; Rickman, Catherine Bowes; Allingham, R Rand; Hauser, Michael A

    2011-04-08

    To identify the genes expressed in normal human trabecular meshwork tissue, a tissue critical to the pathogenesis of glaucoma. Total RNA was extracted from human trabecular meshwork (HTM) harvested from 3 different donors. Extracted RNA was used to synthesize individual SAGE (serial analysis of gene expression) libraries using the I-SAGE Long kit from Invitrogen. Libraries were analyzed using SAGE 2000 software to extract the 17 base pair sequence tags. The extracted sequence tags were mapped to the genome using SAGE Genie map. A total of 298,834 SAGE tags were identified from all HTM libraries (96,842, 88,126, and 113,866 tags, respectively). Collectively, there were 107,325 unique tags. There were 10,329 unique tags with a minimum of 2 counts from a single library. These tags were mapped to known unique Unigene clusters. Approximately 29% of the tags (orphan tags) did not map to a known Unigene cluster. Thirteen percent of the tags mapped to at least 2 Unigene clusters. Sequence tags from many glaucoma-related genes, including myocilin, optineurin, and WD repeat domain 36, were identified. This is the first time SAGE analysis has been used to characterize the gene expression profile in normal HTM. SAGE analysis provides an unbiased sampling of gene expression of the target tissue. These data will provide new and valuable information to improve understanding of the biology of human aqueous outflow.

  19. Vitrification affects nuclear maturation and gene expression of immature human oocytes

    Directory of Open Access Journals (Sweden)

    Abbas Shahedi

    2017-02-01

    Full Text Available Background: Vitrification of oocytes is a fast-freezing technique, which may affect the quality of the human oocyte, and consequently affects the embryo development, pregnancy and birth. The aim of the current study was to investigate the consequence of in-vitro vitrification on maturation status of immature human oocytes, additionally, expression levels of stress, and apoptosis related genes. Materials and Methods: The total of 213 human immature oocytes which routinely discarded from assisted reproduction clinics were collected and divided into two groups including: (I fresh germinal vesicle (GV oocytes (n=106 (matured in-vitro  (fIVM , and  (II GV oocytes (n=107 that initially vitrified, then matured in  in-vitro (vIVM. After 36 hours of incubation, the oocytes were evaluated for nuclear maturation and expression level of DNA methyltransferase (DNMT1, stress related genes (Sod1 and Hsp70, and apoptotic related genes (Bax and Bcl-2 by quantitative Real-Time PCR. Results: Oocyte maturation rates were reduced in vIVM compared to fIVM oocytes (P=0.001. The expression of stress (Sod1 and Hsp70, and apoptotic-related genes (Bax and Bcl-2 in vIVM were significantly higher compared to the fIVM group. Additionally, pro-apoptotic gene up-regulated 4.3 times more than anti-apoptotic gene in vIVM oocyte. However, DNMT1 gene expression was reduced in vIVM oocyte (P = 0.047. Conclusions: The low survival rate of vitrified In-vitro matured GV oocytes could definitely be explained by the alterations of their gene expression profile. 

  20. Gene expression and functional annotation of the human ciliary body epithelia.

    Directory of Open Access Journals (Sweden)

    Sarah F Janssen

    Full Text Available PURPOSE: The ciliary body (CB of the human eye consists of the non-pigmented (NPE and pigmented (PE neuro-epithelia. We investigated the gene expression of NPE and PE, to shed light on the molecular mechanisms underlying the most important functions of the CB. We also developed molecular signatures for the NPE and PE and studied possible new clues for glaucoma. METHODS: We isolated NPE and PE cells from seven healthy human donor eyes using laser dissection microscopy. Next, we performed RNA isolation, amplification, labeling and hybridization against 44×k Agilent microarrays. For microarray conformations, we used a literature study, RT-PCRs, and immunohistochemical stainings. We analyzed the gene expression data with R and with the knowledge database Ingenuity. RESULTS: The gene expression profiles and functional annotations of the NPE and PE were highly similar. We found that the most important functionalities of the NPE and PE were related to developmental processes, neural nature of the tissue, endocrine and metabolic signaling, and immunological functions. In total 1576 genes differed statistically significantly between NPE and PE. From these genes, at least 3 were cell-specific for the NPE and 143 for the PE. Finally, we observed high expression in the (NPE of 35 genes previously implicated in molecular mechanisms related to glaucoma. CONCLUSION: Our gene expression analysis suggested that the NPE and PE of the CB were quite similar. Nonetheless, cell-type specific differences were found. The molecular machineries of the human NPE and PE are involved in a range of neuro-endocrinological, developmental and immunological functions, and perhaps glaucoma.