Glucosylsphingosine accumulation in mice and patients with type 2 Gaucher disease begins early in gestation.

Abstract:

:Gaucher disease, the most common of the sphingolipidoses, results from the inherited deficiency of the enzyme glucocerebrosidase (EC 3.2.1.45). Although type 2 (acute neuronopathic) Gaucher disease is associated with rapidly progressive and fatal neurologic deterioration, the pathophysiologic mechanisms leading to the neurologic symptoms and early demise remain uncharacterized. While the pathology encountered in Gaucher disease has been attributed to glucocerebroside storage, glucosylsphingosine (Glc-sph), a cytotoxic compound, also accumulates in the tissues. Elevations of brain Glc-sph have been reported in patients with types 2 and 3 Gaucher disease. In this study, Glc-sph levels were measured using HPLC in tissues from mice with type 2 Gaucher disease created with a null glucocerebrosidase allele. Compared with unaffected littermates, homozygous mice with type 2 Gaucher disease had approximately a 100-fold elevation of Glc-sph in brain, as well as elevated levels in other tissues. This accumulation was detected in utero by E 13 and increased progressively throughout gestation. Similarly, elevated Glc-sph levels were seen in human fetuses with type 2 Gaucher disease, indicating that therapy initiated after birth may be too late to prevent the sequelae of progressive neurologic damage that begins early in gestation. These findings suggest that the accumulation of Glc-sph may be responsible for the rapid demise of mice with type 2 Gaucher disease and the devastating clinical course seen in patients with type 2 Gaucher disease.

journal_name

Pediatr Res

journal_title

Pediatric research

authors

Orvisky E,Sidransky E,McKinney CE,Lamarca ME,Samimi R,Krasnewich D,Martin BM,Ginns EI

doi

10.1203/00006450-200008000-00018

subject

Has Abstract

pub_date

2000-08-01 00:00:00

pages

233-7

issue

2

eissn

0031-3998

issn

1530-0447

journal_volume

48

pub_type

杂志文章
  • Appearance of sleep cycling after birth in term neonates: an electro-physiologic study.

    abstract:BACKGROUND:Appearance of sleep cycling has been associated with good outcome in term and preterm infants, but the normal time of its appearance has not been determined. The objectives of this study were, to correlate the time of sleep cycling appearance and the length of quiet sleep in neonates with different degrees o...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1038/s41390-019-0560-z

    authors: Abramsky R,Stavsky M,Novack V,Shany E

    更新日期:2020-03-01 00:00:00

  • Comparative proteomic profiles of the normal and aganglionic hindgut in human Hirschsprung disease.

    abstract:BACKGROUND:Hirschsprung disease (HSCR) is the third most common congenital disorder of the gastrointestinal tract. This study aims to elucidate changes in protein expression between the normal and aganglionic hindgut in human HSCR. METHODS:The biopsies were obtained from the normal and aganglionic hindgut in human HSC...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1038/pr.2014.33

    authors: Zhang SC,Chen F,Jiang KL,Yuan ZW,Wang WL

    更新日期:2014-06-01 00:00:00

  • Exercise-associated prevention of adult cardiovascular disease in children and adolescents: monocytes, molecular mechanisms, and a call for discovery.

    abstract::Atherosclerosis originates in childhood and adolescence. The goal of this review is to highlight how exercise and physical activity during childhood and adolescence, critical periods of growth and development, can prevent adult cardiovascular disease (CVD), particularly through molecular mechanisms of monocytes, a key...

    journal_title:Pediatric research

    pub_type: 杂志文章,评审

    doi:10.1038/s41390-019-0581-7

    authors: Cooper DM,Radom-Aizik S

    更新日期:2020-01-01 00:00:00

  • Proportional assist ventilation decreases thoracoabdominal asynchrony and chest wall distortion in preterm infants.

    abstract::Thoracoabdominal asynchrony (TAA) and chest wall distortion (CWD) are commonly seen in preterm infants secondary to a highly compliant rib cage and poor compensation of distorting forces by inspiratory rib cage muscles. Continuous positive airway pressure (CPAP) reduces TAA and CWD by stenting the chest wall. We hypot...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-200102000-00008

    authors: Musante G,Schulze A,Gerhardt T,Everett R,Claure N,Schaller P,Bancalari E

    更新日期:2001-02-01 00:00:00

  • Effects of vitamin D supplementation on circulating concentrations of growth factors and immune-mediators in healthy women during pregnancy.

    abstract:BACKGROUND:For the second aim of the Kellogg Foundation grant, this double-blind RCT investigated the impact of plasma vitamin D metabolite 25-hydroxyvitamin D (25(OH)D) on plasma immune-mediators during pregnancy. We hypothesized that higher 25(OH)D concentrations would associate with reduced pro-inflammatory and incr...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1038/s41390-020-0885-7

    authors: Khatiwada A,Wolf BJ,Mulligan JK,Shary JR,Hewison M,Baatz JE,Newton DA,Hawrylowicz C,Hollis BW,Wagner CL

    更新日期:2020-04-20 00:00:00

  • Corticosterone metabolism and the incorporation of leucine, uridine, and thymidine into fetal mouse brain.

    abstract::The change in the pattern of biotransformation of [14C]corticosterone in fetal mouse brain between gestational day 14 and 17 increased the proportion of unchanged hormone from 9-75%. A sharp decrease in the in vitro incorporation of [14C]leucine, [3H]uridine, and [3H]thymidine into incubated brain coincided with this ...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-197812000-00011

    authors: Tye LM,Michaud NJ,Burton AF

    更新日期:1978-12-01 00:00:00

  • Diffusion tensor imaging in preterm infants with punctate white matter lesions.

    abstract::Our aim was to compare white matter (WM) microstructure in preterm infants with and without punctate WM lesions on MRI using tract-based spatial statistics (TBSS) and probabilistic tractography. We studied 23 preterm infants with punctate lesions, median GA at birth 30 (25-35) wk, and 23 GA- and sex-matched preterm co...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/PDR.0b013e3182182836

    authors: Bassi L,Chew A,Merchant N,Ball G,Ramenghi L,Boardman J,Allsop JM,Doria V,Arichi T,Mosca F,Edwards AD,Cowan FM,Rutherford MA,Counsell SJ

    更新日期:2011-06-01 00:00:00

  • Serum insulin-like growth factors I and II concentrations and growth hormone and insulin responses to arginine infusion in children with protein-energy malnutrition before and after nutritional rehabilitation.

    abstract::Serum insulin, growth hormone (GH), insulin-like growth factors (IGFs) I and II, cortisol, and albumin concentrations were measured in 15 children with kwashiorkor, 15 with marasmic-kwashiorkor, and 21 with marasmus, before and in the survivors, after nutritional rehabilitation, as well as in 10 underweight and eight ...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-198611000-00012

    authors: Soliman AT,Hassan AE,Aref MK,Hintz RL,Rosenfeld RG,Rogol AD

    更新日期:1986-11-01 00:00:00

  • Cardiomyocyte regeneration from circulating bone marrow cells in mice.

    abstract::We investigated the role of circulating bone marrow cells (BMC) in cardiomyocyte regeneration. BMC, isolated from transgenic mice expressing enhanced green fluorescent protein (GFP), were transplanted into lethally irradiated C57BL6 mice. Five weeks after bone marrow transplantation (BMT), flow cytometric analysis for...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/01.PDR.0000078275.14079.77

    authors: Kuramochi Y,Fukazawa R,Migita M,Hayakawa J,Hayashida M,Uchikoba Y,Fukumi D,Shimada T,Ogawa S

    更新日期:2003-09-01 00:00:00

  • The adaptation of neonatal blood to metabolic acidosis and its effect on cisternal oxygen tension.

    abstract::In eight newborn lambs, the adaption of blood to acidosis was studied by sequential measurements of P50 in vitro (pH 7.4; 37 degrees C) and P50 in vivo (animal's pH and temperature, 39 degrees C) during the course of HCl-induced metabolic acidosis. The benefit of the change in both P50 on tissue oxygen tension was stu...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:

    authors: Berthiaume Y,Bureau MA,Bégin R

    更新日期:1981-05-01 00:00:00

  • Spontaneous gonadotropin and testosterone concentration profiles in prepubertal and pubertal boys: temporal relationship between luteinizing hormone and testosterone.

    abstract::To investigate the detailed pattern of change in circulating gonadotropin and testosterone concentrations around the onset of puberty and to determine the temporal relationship between the gonadotropin and testosterone secretion, plasma gonadotropin and testosterone were measured at 20-min intervals for 24 h in 21 nor...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-199308000-00026

    authors: Goji K,Tanikaze S

    更新日期:1993-08-01 00:00:00

  • Gestational changes in renal responsiveness to cortisol in the ovine fetus.

    abstract::The ontogenetic renal responsiveness to exogenous cortisol was examined in the chronically cannulated ovine fetus. The contribution of effects at proximal and distal tubule of the kidney were studied also. Cortisol (81.5 micrograms/h) was infused into immature ovine fetuses (mean gestational age -113.9 days) on five o...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-198907000-00002

    authors: Towstoless MK,McDougall JG,Wintour EM

    更新日期:1989-07-01 00:00:00

  • Low antithrombin III levels in neonates with idiopathic respiratory distress syndrome: poor prognosis.

    abstract::Automated microanalytic chromogenic coagulation assays allow serial monitoring of critically ill newborn infants. In this study 84 premature infants [26 healthy prematures and 58 neonates with idiopathic respiratory distress syndrome (IRDS)] were studied daily during the first week of life, to investigate the possible...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-198403000-00012

    authors: Peters M,Ten Cate JW,Breederveld C,De Leeuw R,Emeis J,Koppe J

    更新日期:1984-03-01 00:00:00

  • Comparing near-infrared spectroscopy devices and their sensors for monitoring regional cerebral oxygen saturation in the neonate.

    abstract:BACKGROUND:Near-infrared spectroscopy (NIRS) is an upcoming clinical method for monitoring regional cerebral oxygen saturation (rScO2) in neonates. There is a growing market offering different devices and sensors. Even though this technique is increasingly clinically applied, little is known about the similarities and/...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1038/pr.2013.133

    authors: Dix LM,van Bel F,Baerts W,Lemmers PM

    更新日期:2013-11-01 00:00:00

  • Fish oil supplementation in pregnancy modifies neonatal progenitors at birth in infants at risk of atopy.

    abstract::Dietary n-3 polyunsaturated fatty acids (PUFA) may represent a mode of allergy prevention. Cord blood (CB) CD34+ hemopoietic progenitors are altered in infants at risk of atopy. We therefore studied the effects of dietary n-3 PUFA supplementation during pregnancy on numbers and function of progenitors in neonates at h...

    journal_title:Pediatric research

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1203/01.PDR.0000148279.72611.1D

    authors: Denburg JA,Hatfield HM,Cyr MM,Hayes L,Holt PG,Sehmi R,Dunstan JA,Prescott SL

    更新日期:2005-02-01 00:00:00

  • Clinical utility of endomyocardial biopsies in the diagnosis of arrhythmogenic right ventricular cardiomyopathy in children.

    abstract:BACKGROUND:Histomorphometry of endomyocardial biopsies is one component of arrhythmogenic right ventricular cardiomyopathy (ARVC) diagnosis, although there is a need for stricter diagnostic criteria for this disease in pediatrics. The clinical utility of biopsy analysis as a component of ARVC diagnosis was evaluated in...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1038/s41390-018-0093-x

    authors: Sreetharan S,MacIntyre CJ,Fatah M,Warren AE,Wilson GJ,Hamilton RM

    更新日期:2018-10-01 00:00:00

  • Mucosal immune response in a case of sudden infant death syndrome.

    abstract::A prospective study to define the normal patterns of development of mucosal immunity in 263 children provided a unique opportunity to study the mucosal immune response in an infant who unexpectedly died from sudden infant death syndrome. The subject initially had a normal pattern of mucosal immune function, which was ...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-199306000-00003

    authors: Gleeson M,Clancy RL,Cripps AW

    更新日期:1993-06-01 00:00:00

  • Permeability of the blood brain barrier for 125I-albumin-bound bilirubin in newborn piglets.

    abstract::Permeability of the blood brain barrier (BBB) for bilirubin and 125I-albumin was studied in 2-d- and 2-wk-old piglets. 125I-albumin was given by bolus at the beginning of each study. Hyperbilirubinemia was produced by an initial bolus infusion of bilirubin and sustained at a plasma bilirubin:albumin molar ratio of app...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-198905000-00005

    authors: Lee C,Oh W,Stonestreet BS,Cashore WJ

    更新日期:1989-05-01 00:00:00

  • Surgery requiring general anesthesia in preterm infants is associated with altered brain volumes at term equivalent age and neurodevelopmental impairment.

    abstract:BACKGROUND:The aim of the study was to describe and contrast the brain development and outcome among very preterm infants that were and were not exposed to surgery requiring general anesthesia prior to term equivalent age (TEA). METHODS:Preterm infants born ≤30 weeks' gestation who did (n = 25) and did not (n = 59) ha...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1038/s41390-020-1030-3

    authors: Walsh BH,Paul RA,Inder TE,Shimony JS,Smyser CD,Rogers CE

    更新日期:2020-06-23 00:00:00

  • A model for educational simulation of hemodynamic transitions at birth.

    abstract::Birth is characterized by swift and complex transitions in hemodynamic and respiratory variables. Unrecognized pathologies or incidents may quickly become fatal or cause permanent damage. This article introduces an essential component of an acute perinatal care simulator, namely a model for educational simulation of n...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/PDR.0b013e3181c2def3

    authors: Sá-Couto CD,Andriessen P,Van Meurs WL,Ayres-de-Campos D,Sá-Couto PM

    更新日期:2010-02-01 00:00:00

  • Therapeutic hypothermia modulates complement factor C3a and C5a levels in a rat model of hypoxic ischemic encephalopathy.

    abstract:BACKGROUND:Therapeutic hypothermia (HT) is the only intervention that improves outcomes in neonatal hypoxic-ischemic encephalopathy (HIE). However, the multifactorial mechanisms by which HT impacts HIE are incompletely understood. The complement system plays a major role in the pathogenesis of ischemia-reperfusion inju...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1038/pr.2016.271

    authors: Shah TA,Nejad JE,Pallera HK,Lattanzio FA,Farhat R,Kumar PS,Hair PS,Bass WT,Krishna NK

    更新日期:2017-04-01 00:00:00

  • Response to calcium of skinned gallbladder smooth muscle from newborn and adult guinea pigs.

    abstract::Guinea pig gallbladder smooth muscle contractility undergoes a period of postnatal maturation. Because tissues from adult animals contract more forcefully than tissues from newborn animals when stimulated with agonists that activate the contractile process through different mechanisms (receptor activation, membrane de...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-199010000-00007

    authors: Lambert R,Ryan JP

    更新日期:1990-10-01 00:00:00

  • Gastrointestinal pathogens in anti-FH antibody positive and negative Hemolytic Uremic Syndrome.

    abstract:BACKGROUND:Prodromal symptoms are frequently reported in the atypical form of Hemolytic uremic syndrome (aHUS) suggesting implication of infectious triggers. Some pathogens may also play a role in the mechanisms of production of autoantibody directed against Factor H (FH), a complement regulator, leading to aHUS. METH...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1038/s41390-018-0009-9

    authors: Togarsimalemath SK,Si-Mohammed A,Puraswani M,Gupta A,Vabret A,Liguori S,Mariani-Kurkdjian P,Bagga A,Dragon-Durey MA

    更新日期:2018-07-01 00:00:00

  • Gender-specific relationship between prenatal exposure to phthalates and intrauterine growth restriction.

    abstract:BACKGROUND:No study has examined the association between prenatal phthalate exposure and intrauterine growth retardation (IUGR). This study aimed to investigate whether prenatal exposure to phthalates was associated with increased risk of IUGR. METHODS:A total of 126 mother-newborn pairs, including 42 IUGR cases and 8...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1038/pr.2014.103

    authors: Zhao Y,Chen L,Li LX,Xie CM,Li D,Shi HJ,Zhang YH

    更新日期:2014-10-01 00:00:00

  • Cerebral metabolism in the newborn lamb with polycythemia.

    abstract::Infants with polycythemia and hyperviscosity are known to have a reduced cerebral blood flow. Eight newborn lambs were studied to determine what effect the reduction in cerebral blood flow might have on the cerebral delivery and uptake of oxygen, glucose, lactate, pyruvate, beta-hydroxybutyrate, and acetoacetate. Meas...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-198803000-00019

    authors: Rosenkrantz TS,Philipps AF,Skrzypczak PS,Raye JR

    更新日期:1988-03-01 00:00:00

  • Selective impairment of taurine transport by cyclosporin A in a human placental cell line.

    abstract::We investigated, using a human placental choriocarcinoma cell line as a model, the effects of the immunosuppressive drug cyclosporin A on several placental transport systems mediating the transfer of glucose and amino acids from mother to fetus. The results of the investigation show that the transport system responsib...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-199207000-00024

    authors: Ramamoorthy S,Leibach FH,Mahesh VB,Ganapathy V

    更新日期:1992-07-01 00:00:00

  • Natural history, outcome, and treatment efficacy in children and adults with glutaryl-CoA dehydrogenase deficiency.

    abstract::Glutaryl-CoA dehydrogenase (GCDH) deficiency is a rare inborn disorder of L-lysine, L-hydroxylysine, and L-tryptophan metabolism complicated by striatal damage during acute encephalopathic crises. Three decades after its description, the natural history and how to treat this disorder are still incompletely understood....

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/01.pdr.0000219387.79887.86

    authors: Kölker S,Garbade SF,Greenberg CR,Leonard JV,Saudubray JM,Ribes A,Kalkanoglu HS,Lund AM,Merinero B,Wajner M,Troncoso M,Williams M,Walter JH,Campistol J,Martí-Herrero M,Caswill M,Burlina AB,Lagler F,Maier EM,Schwahn B

    更新日期:2006-06-01 00:00:00

  • Fetal cartilage xylosyltransferase activity and skeletal growth in sheep.

    abstract::The activity of UDP-D-xylose:proteoglycan core protein beta-D-xylosyltransferase (EC 2.4.2.26), the enzyme that catalyzes the initiation of the polysaccharide chain linkage to the core protein of proteoglycans, was measured in costal cartilage from 20 fetal sheep of 65-138 days gestation. Activity of the enzyme was es...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1203/00006450-198512000-00003

    authors: Morriss FH Jr,Fitzgerald B,Riddle LM

    更新日期:1985-12-01 00:00:00

  • Determinants of neurological outcome in neonates with congenital heart disease following heart surgery.

    abstract:BACKGROUND:The objective was to determine the association between perioperative risk factors and brain imaging abnormalities on neurologic outcome in neonates with hypoplastic left heart syndrome (HLHS) or d-Transposition of the great arteries (d-TGA) who underwent cardiac surgery including cardiopulmonary bypass. MET...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1038/s41390-020-1085-1

    authors: Kuhn VA,Carpenter JL,Zurakowski D,Reitz JG,Tague L,Donofrio MT,Murnick J,Axt-Fliedner R,Limperopoulos C,Yerebakan C

    更新日期:2020-07-25 00:00:00

  • Food sensitization in preschool Egyptian children with recurrent wheezing.

    abstract:BACKGROUND:Food allergy is common in children with prevalence up to 10%. We assessed the clinico-laboratory characteristics and frequency of food sensitization to the commonly consumed food among upper Egyptian preschool children with recurrent wheezy chest. METHODS:This cross-sectional descriptive study was conducted...

    journal_title:Pediatric research

    pub_type: 杂志文章

    doi:10.1038/s41390-020-0960-0

    authors: Abdallah AM,Osman NS,Mohammad HA,Metwalley KA,Embaby M,ElMelegy TT

    更新日期:2020-10-01 00:00:00