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1.
Nature ; 626(7999): 517-522, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38356066

ABSTRACT

Lifted Kramers spin degeneracy (LKSD) has been among the central topics of condensed-matter physics since the dawn of the band theory of solids1,2. It underpins established practical applications as well as current frontier research, ranging from magnetic-memory technology3-7 to topological quantum matter8-14. Traditionally, LKSD has been considered to originate from two possible internal symmetry-breaking mechanisms. The first refers to time-reversal symmetry breaking by magnetization of ferromagnets and tends to be strong because of the non-relativistic exchange origin15. The second applies to crystals with broken inversion symmetry and tends to be comparatively weaker, as it originates from the relativistic spin-orbit coupling (SOC)16-19. A recent theory work based on spin-symmetry classification has identified an unconventional magnetic phase, dubbed altermagnetic20,21, that allows for LKSD without net magnetization and inversion-symmetry breaking. Here we provide the confirmation using photoemission spectroscopy and ab initio calculations. We identify two distinct unconventional mechanisms of LKSD generated by the altermagnetic phase of centrosymmetric MnTe with vanishing net magnetization20-23. Our observation of the altermagnetic LKSD can have broad consequences in magnetism. It motivates exploration and exploitation of the unconventional nature of this magnetic phase in an extended family of materials, ranging from insulators and semiconductors to metals and superconductors20,21, that have been either identified recently or perceived for many decades as conventional antiferromagnets21,24,25.

2.
ACS Nano ; 14(12): 17554-17564, 2020 Dec 22.
Article in English | MEDLINE | ID: mdl-33236903

ABSTRACT

The coupling of real and momentum space is utilized to tailor electronic properties of the collinear metallic antiferromagnet Mn2Au by aligning the real space Néel vector indicating the direction of the staggered magnetization. Pulsed magnetic fields of 60 T were used to orient the sublattice magnetizations of capped epitaxial Mn2Au(001) thin films perpendicular to the applied field direction by a spin-flop transition. The electronic structure and its corresponding changes were investigated by angular-resolved photoemission spectroscopy with photon energies in the vacuum-ultraviolet, soft, and hard X-ray range. The results reveal an energetic rearrangement of conduction electrons propagating perpendicular to the Néel vector. They confirm previous predictions on the origin of the Néel spin-orbit torque and anisotropic magnetoresistance in Mn2Au and reflect the combined antiferromagnetic and spin-orbit interaction in this compound leading to inversion symmetry breaking.

3.
Nat Commun ; 8(1): 1006, 2017 10 18.
Article in English | MEDLINE | ID: mdl-29044121

ABSTRACT

The premartensite phase of shape memory and magnetic shape memory alloys (MSMAs) is believed to be a precursor state of the martensite phase with preserved austenite phase symmetry. The thermodynamic stability of the premartensite phase and its relation to the martensitic phase is still an unresolved issue, even though it is critical to the understanding of the functional properties of MSMAs. We present here unambiguous evidence for macroscopic symmetry breaking leading to robust Bain distortion in the premartensite phase of 10% Pt-substituted Ni2MnGa. We show that the robust Bain-distorted premartensite (T2) phase results from another premartensite (T1) phase with preserved cubic-like symmetry through an isostructural phase transition. The T2 phase finally transforms to the martensite phase with additional Bain distortion on further cooling. Our results demonstrate that the premartensite phase should not be considered as a precursor state with the preserved symmetry of the cubic austenite phase.

4.
Nat Commun ; 7: 12671, 2016 08 26.
Article in English | MEDLINE | ID: mdl-27561795

ABSTRACT

Antiferromagnetic spintronics is a rapidly growing field, which actively introduces new principles of magnetic storage. Despite that, most applications have been suggested for collinear antiferromagnets. In this study, we consider an alternative mechanism based on long-range helical order, which allows for direct manipulation of the helicity vector. As the helicity of long-range homogeneous spirals is typically fixed by the Dzyaloshinskii-Moriya interactions, bi-stable spirals (left- and right-handed) are rare. Here, we report a non-collinear room-temperature antiferromagnet in the tetragonal Heusler group. Neutron diffraction reveals a long-period helix propagating along its tetragonal axis. Ab-initio analysis suggests its pure exchange origin and explains its helical character resulting from a large basal plane magnetocrystalline anisotropy. The actual energy barrier between the left- and right-handed spirals is relatively small and might be easily overcome by magnetic pulse, suggesting Pt2MnGa as a potential candidate for non-volatile magnetic memory.

5.
Phys Rev Lett ; 109(24): 246601, 2012 Dec 14.
Article in English | MEDLINE | ID: mdl-23368355

ABSTRACT

Spin valves have revolutionized the field of magnetic recording and memory devices. Spin valves are generally realized in thin film heterostructures, where two ferromagnetic (FM) layers are separated by a nonmagnetic conducting layer. Here, we demonstrate spin-valve-like magnetoresistance at room temperature in a bulk ferrimagnetic material that exhibits a magnetic shape memory effect. The origin of this unexpected behavior in Mn(2)NiGa has been investigated by neutron diffraction, magnetization, and ab initio theoretical calculations. The refinement of the neutron diffraction pattern shows the presence of antisite disorder where about 13% of the Ga sites are occupied by Mn atoms. On the basis of the magnetic structure obtained from neutron diffraction and theoretical calculations, we establish that these antisite defects cause the formation of FM nanoclusters with parallel alignment of Mn spin moments in a Mn(2)NiGa bulk lattice that has antiparallel Mn spin moments. The direction of the Mn moments in the soft FM cluster reverses with the external magnetic field. This causes a rotation or tilt in the antiparallel Mn moments at the cluster-lattice interface resulting in the observed asymmetry in magnetoresistance.

6.
Rev Sci Instrum ; 82(9): 093901, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21974594

ABSTRACT

We report a bandpass ultraviolet photon detector for inverse photoemission spectroscopy with energy resolution of 82 ± 2 meV. The detector (Sr(0.7)Ca(0.3)F(2)/acetone) consists of Sr(0.7)Ca(0.3)F(2) entrance window with energy transmission cutoff of 9.85 eV and acetone as detection gas with 9.7 eV photoionization threshold. The response function of the detector, measured using synchrotron radiation, has a nearly Gaussian shape. The n = 1 image potential state of Cu(100) and the Fermi edge of silver have been measured to demonstrate the improvement in resolution compared to the CaF(2)/acetone detector. To show the advantage of improved resolution of the Sr(0.7)Ca(0.3)F(2)/acetone detector, the metal to semiconductor transition in Sn has been studied. The pseudogap in the semiconducting phase of Sn could be identified, which is not possible with the CaF(2)/acetone detector because of its worse resolution.

7.
Rev Sci Instrum ; 81(4): 043907, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20441350

ABSTRACT

We present a design of a compact and versatile sample holder meant for studying complex (ternary) metallic crystals that require sputtering and annealing to high temperatures under ultrahigh vacuum (10(-10) mbar range) for obtaining the clean, ordered and stoichiometric surface. A resistive heater is fixed to the sample holder and not to the sample plate, and thus can be thoroughly degassed initially to high temperatures without heating the sample. The heater, which is mounted vertically on the sample holder frame, slides into the sample plate of rectangular cross-section during sample transfer. For efficient cooling that is required for adlayer deposition, Cu braids can be pressed on the sample plate from both sides through a screw mechanism. The sample holder has 5 degrees of freedom including a tilt rotation. The sample holder has been used to study different metal surfaces such as ferromagnetic shape memory alloys, alkali metal and Mn adlayers on Al-Pd-Mn quasicrystal, aluminum metal, and Al-Mn alloys. Here, our recent results on temperature dependent low energy electron diffraction study of Ni(2)MnGa(100) are presented.

8.
Placenta ; 31(2): 134-43, 2010 Feb.
Article in English | MEDLINE | ID: mdl-20036773

ABSTRACT

Poor folate status during pregnancy can lead to elevated maternal plasma levels of homocysteine (Hcy) with associated pregnancy complications and adverse neonatal outcomes, suggesting placental metabolism of Hcy might be an important determinant in influencing fetal development. The metabolic pathways for Hcy in placenta are not well defined. In this study we examined the gene expression of key enzymes involved in Hcy metabolism in first trimester and term human placenta to determine which metabolic pathways prevail. Expression of mRNA for methionine synthase and 5,10-methylene tetrahydrofolate reductase, enzymes involved in the methionine cycle and responsible for the re-methylation of Hcy to methionine, were expressed at similar levels between first trimester and term and in comparison to human liver as positive control. In contrast, cystathionine beta-synthase mRNA expression was markedly lower than that in liver at both gestational periods. Betaine-homocysteine methyltransferase mRNA was undetectable at either gestational age. These data suggest that re-methylation of Hcy using methyl donation from 5-methyltetrahydrofolate is the prevalent pathway, indicating a marked reliance on folate availability. This led to further investigations examining the expression and localisation of folate transporters in first trimester and term placenta. Folate receptor alpha (FRalpha) was highly polarised to the microvillous plasma membrane (MVM) of the syncytiotrophoblast at both gestational periods, a distribution shared by the proton-coupled folate transporter which co-localised with FRalpha. Reduced folate carrier was distributed to both MVM and basal syncytiotrophoblast plasma membranes at term suggesting a role at both loci, and in first trimester was localised to MVM as well as cytotrophoblast plasma membranes. These data support the concept that placental folate transport is established early in pregnancy, providing folate for utilisation in placental Hcy metabolism.


Subject(s)
Carrier Proteins/metabolism , Folic Acid/metabolism , Homocysteine/metabolism , Membrane Transport Proteins/metabolism , Placenta/metabolism , Pregnancy Proteins/metabolism , Receptors, Cell Surface/metabolism , Trophoblasts/metabolism , 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase/genetics , 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase/metabolism , Carrier Proteins/genetics , Cell Membrane/enzymology , Cell Membrane/metabolism , Cell Polarity , Cystathionine beta-Synthase/genetics , Cystathionine beta-Synthase/metabolism , Female , Fluorescent Antibody Technique, Indirect , Folate Receptors, GPI-Anchored , Humans , Membrane Transport Proteins/genetics , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Methylenetetrahydrofolate Reductase (NADPH2)/metabolism , Placenta/enzymology , Placenta/ultrastructure , Pregnancy , Pregnancy Proteins/genetics , Pregnancy Trimester, First , Protein Transport , Proton-Coupled Folate Transporter , RNA, Messenger/metabolism , Receptors, Cell Surface/genetics , Reduced Folate Carrier Protein , Reverse Transcriptase Polymerase Chain Reaction , Term Birth , Trophoblasts/enzymology , Trophoblasts/ultrastructure
9.
J Phys Condens Matter ; 21(40): 405005, 2009 Oct 07.
Article in English | MEDLINE | ID: mdl-21832407

ABSTRACT

Pseudomorphic growth of thin elemental metal films is often observed on a variety of crystalline solids. On quasicrystalline surfaces with their complex structure and the absence of translational periodicity, the situation is different since elemental metals do not exhibit quasicrystalline order, and hence the specific interaction between overlayer and substrate is decisive. Here we study the growth of manganese films on an icosahedral i-Al-Pd-Mn alloy with a view to establishing the growth mode and electronic structure. Although we observe an exponential intensity variation of the adlayer and substrate related x-ray photoemission spectroscopy (XPS) peaks, low energy electron diffraction (LEED) shows that Mn adlayers do not exhibit quasicrystallinity. The detailed structure of the Mn 2p core level line reveals considerable electronic structure differences between the quasicrystalline and elemental metal environment. Evidence of a substantial local magnetic moment on the Mn atoms in the overlayer (about 2.8  µ(B)) is obtained from the Mn 3s exchange splitting.

10.
J Obstet Gynaecol ; 28(7): 678-82, 2008 Oct.
Article in English | MEDLINE | ID: mdl-19065359

ABSTRACT

The incidence of congenital heart defects in Asian children is significantly higher than in non-Asian, however little data are available for other anomalies. The Fetal Management Unit at St Mary's Hospital is a tertiary referral centre for prenatal diagnosis in the north-west region. Using data collected after routine prenatal ultrasonography between 1996-2001, we show that in a defined population there was a significant reduction in the incidence of central nervous system (CNS) anomalies over this period but not in other anomalies. Furthermore, fetal congenital anomalies were diagnosed in a higher proportion of Asian than non-Asian women, with CNS, cardiac, bowel, thoracic and facial anomalies and hydrops being statistically significant. Monitoring local trends in a multiethnic community is essential for appropriate counselling, providing parents with an informed choice and in assessing the effectiveness of interventions.


Subject(s)
Congenital Abnormalities/diagnostic imaging , Ultrasonography, Prenatal , Asia/ethnology , Central Nervous System/abnormalities , Congenital Abnormalities/epidemiology , Face/abnormalities , Female , Heart Defects, Congenital/diagnostic imaging , Heart Defects, Congenital/epidemiology , Humans , Hydrops Fetalis/diagnostic imaging , Hydrops Fetalis/epidemiology , Intestines/abnormalities , Limb Deformities, Congenital/diagnostic imaging , Limb Deformities, Congenital/epidemiology , Pregnancy , Thorax/abnormalities , United Kingdom
11.
Child Care Health Dev ; 33(2): 206-12, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17291325

ABSTRACT

OBJECTIVE: To evaluate the impact of a shared care approach in clinical management with a drug liaison midwife (DLM) service for mothers and infants established in 1995-1996 in an inner city area and to address the problem of congenital abnormality and microcephaly with fetal drug exposure. METHODS: Descriptive analysis of data in live births of women enrolled in a methadone maintenance programme in 1991-1994 (n = 78) and 1997-2001 (n = 98), including time spent in hospital, treatment for neonatal abstinence syndrome (NAS), admission to the neonatal medical unit (NMU) and follow-up for child health checks. RESULTS: In 1997-2001 compared with 1991-1994, the mothers used more methadone in the last week of pregnancy (median 40.0 mg/day vs. 21.5 mg/day, P = 0.0006) and there were more preterm deliveries (36% vs. 21%, P = 0.03). The infants spent less time in hospital (median 5 days vs. 28 days, P < 0.0001), a smaller proportion had treatment for NAS (14% vs. 79%, P < 0.0001), and NMU admission was reduced (median 14 days vs. 26 days, P < 0.0003). Neonatal convulsions (P = 0.0001) and jaundice (P < 0.001) occurred less frequently, and more infants were breastfed (P = 0.001). One infant in each study group had a cleft palate and none had microcephaly. Child health checks for 18-24 months showed a favourable outcome in 1997-2001. CONCLUSIONS: We altered antenatal care and modified neonatal management, subsequently infants spent less time in hospital and NMU admissions were reduced with less NAS treatment. Congenital abnormalities and microcephaly were not common and as regular child health checks were possible, the impact of the DLM service in shared management merits further investigation, for mother-infant bonding and developmental outcome.


Subject(s)
Delivery of Health Care/organization & administration , Infant Care/standards , Maternal Health Services/organization & administration , Methadone/adverse effects , Midwifery/organization & administration , Narcotics/adverse effects , Female , Humans , Infant, Newborn , Interprofessional Relations , Length of Stay , Microcephaly/chemically induced , Microcephaly/epidemiology , Neonatal Abstinence Syndrome/epidemiology , Outcome and Process Assessment, Health Care , Patient-Centered Care/organization & administration , Pregnancy , Pregnancy Outcome , Prenatal Exposure Delayed Effects/chemically induced
12.
Am J Physiol Cell Physiol ; 292(1): C332-41, 2007 Jan.
Article in English | MEDLINE | ID: mdl-16956961

ABSTRACT

Transplacental transfer of taurine, a beta-amino acid essential for fetal and neonatal development, constitutes the primary source of taurine for the fetus. Placental transport of taurine is compromised in pregnancies complicated by intrauterine growth restriction, resulting in a reduced concentration of taurine in cord plasma. This could impact on fetal cellular metabolism as taurine represents the most abundant intracellular amino acid in many fetal cell types. In the present study, we have used pure isolates of fetal platelets and T lymphocytes from cord blood of placentas, from normal, term pregnancies, as fetal cell types to examine the cellular uptake mechanisms for taurine by the system beta transporter and have compared gene and protein expression for the taurine transporter protein (TAUT) in these two cell types. System beta activity in fetal platelets was 15-fold higher compared with fetal T lymphocytes (P < 0.005), mirroring greater TAUT mRNA expression in platelets than T lymphocytes (P < 0.005). Cell-specific differences in TAUT protein moieties were detected with a doublet of 75 and 80 kDa in fetal platelets compared with 114 and 120 kDa in fetal T lymphocytes, with relatively higher expression in platelets. We conclude that greater system beta activity in fetal platelets compared with T lymphocytes is the result of relatively greater TAUT mRNA and protein expression. This study represents the first characterization of amino acid transporters in fetal T lymphocytes.


Subject(s)
Blood Platelets/metabolism , Fetal Blood , Membrane Glycoproteins/blood , Membrane Transport Proteins/blood , T-Lymphocytes/metabolism , Humans , Membrane Glycoproteins/genetics , Membrane Glycoproteins/metabolism , Membrane Transport Proteins/genetics , Membrane Transport Proteins/metabolism , RNA, Messenger/blood
13.
Early Hum Dev ; 83(1): 63-8, 2007 Jan.
Article in English | MEDLINE | ID: mdl-16820273

ABSTRACT

AIM: To explore the associations between a clinical diagnosis of maternal infection (CDMI) and findings on the initial cranial ultrasound scan in very preterm infants. METHODS: Among infants born at less than 32 weeks gestation, cases of CDMI and controls were identified on the basis of routinely available obstetric data. Neonatal cranial ultrasound scans carried out soon after birth were retrospectively reviewed for evidence of parenchymal echodensity (PED), intraventricular haemorrhage (IVH) or PED contiguous with IVH. RESULTS: Any PED was identified in 20/40 (50%) cases of CDMI and 9/30 (30%) of controls. Logistic regression was used to adjust for differences between the two study groups. When compared with normal scans, isolated PED was more likely with CDMI odds ratio, OR (95% confidence interval, CI), 41.8 (2.64, 662) and lower Apgar score at 5 min 2.89 (1.05, 7.98). IVH was more likely with lower gestational age, OR for each completed week of gestation 0.64 (0.46, 0.88) and a protective effect of female sex, OR 0.25 (0.063, 0.98), PED contiguous with IVH was more likely with lower gestational age OR 0.59 (0.336, 1.04). CONCLUSIONS: CDMI may be associated with isolated PED in very preterm infants. We speculate that isolated PED (including "flares") identify infants who have sustained early brain injury because of intrauterine infection. Isolated PED may be a useful intermediate outcome in perinatal cohort studies.


Subject(s)
Brain Diseases/diagnostic imaging , Echoencephalography , Infant, Premature , Pregnancy Complications, Infectious/diagnostic imaging , Apgar Score , Brain Diseases/epidemiology , Brain Diseases/etiology , Female , Humans , Infant, Newborn , Infant, Very Low Birth Weight , Male , Pregnancy , Pregnancy Complications, Infectious/epidemiology , Retrospective Studies , Risk Factors , Skull/diagnostic imaging
14.
Placenta ; 25(6): 496-504, 2004 Jul.
Article in English | MEDLINE | ID: mdl-15135232

ABSTRACT

We investigated the polarization of l-lactate transport in human syncytiotrophoblast by measuring uptake of [(14)C] l-lactate by both microvillous (maternal-facing; MVM) and basal (fetal-facing; BM) plasma membranes. [(14)C] l-lactate uptake by MVM and BM was stimulated in the presence of an inwardly directed H(+)gradient, with a significantly higher uptake in MVM than in BM at initial rate (15.4+/-2.3 vs 5.6+/-0.6 pmol/mg protein/20 sec). Stereospecific inhibition was observed in MVM, with a higher affinity for l-lactate compared with d-lactate. In BM, there was no difference in the inhibition by these two stereoisomers. Inhibition of lactate uptake in both MVM and BM by 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), an inhibitor of monocarboxylate transporter (MCT) activity, indicated MCT-mediated mechanisms across both membranes. Kinetic modelling supported a two-transporter model as the best fit for both MVM and BM, the K(m)of the major component being 6.21 mm and 25.01 mm in MVM and BM respectively. Western blotting and immunolocalization examining the distribution of MCT1 and MCT4, showed that MCT expression was polarized, MCT1 being predominantly localized to BM and MCT4 showing greater abundance on MVM. CD147, a chaperone protein for MCT1 and MCT4, was equally expressed by both membranes. These studies demonstrate that the opposing plasma membranes of human syncytiotrophoblast are polarized with respect to both MCT activity and expression.


Subject(s)
Cell Polarity , Labor, Obstetric , Monocarboxylic Acid Transporters/analysis , Monocarboxylic Acid Transporters/metabolism , Trophoblasts/chemistry , Trophoblasts/metabolism , 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid/pharmacology , Antigens, CD/analysis , Antigens, Neoplasm/analysis , Basigin , Blotting, Western , Carbon Radioisotopes , Cell Membrane/chemistry , Female , Humans , Immunohistochemistry , Kinetics , Lactic Acid/chemistry , Lactic Acid/metabolism , Monocarboxylic Acid Transporters/antagonists & inhibitors , Muscle Proteins/analysis , Pregnancy , Stereoisomerism , Symporters/analysis , Symporters/antagonists & inhibitors
15.
FASEB J ; 18(1): 125-7, 2004 Jan.
Article in English | MEDLINE | ID: mdl-14597568

ABSTRACT

We investigated the expression and activity of arginine transporters and endothelial nitric oxide synthase (eNOS) in human placental microvascular endothelial cells (HPMEC). Using RT-PCR amplification products for eNOS, CAT1, CAT2A, CAT2B, CAT4, 4F2hc (CD98), rBAT and the light chains y+LAT1, y+LAT2, and b0+T1 were detected in HPMEC, but not B0+. Immunohistochemistry and Western blotting confirmed the presence of 4F2hc and CAT1 protein in HPMEC. 4F2hc-light chain dimers were indicated by a shift in molecular mass detected under nonreducing conditions. L-Arginine transport into HPMEC was independent of Na+ or Cl- and was inhibited by the neutral amino acid glutamine, but not by cystine. The Ki for glutamine inhibition was greater in the absence of Na+. Kinetic analysis supported a two-transporter model attributed to system y+L and system y+. Expression of eNOS in HPMEC was detectable by immunohistochemistry and ELISA but not by Western blotting. Activity of eNOS in HPMEC, measured over 48 h, either as the basal production of nitric oxide (NO) or as the accumulation of intracellular cGMP was not detectable. We conclude that HPMEC transport cationic amino acids by systems y+ and y+L and that basal eNOS expression and activity in these cells is low.


Subject(s)
Amino Acid Transport Systems, Basic/metabolism , Arginine/metabolism , Endothelium, Vascular/metabolism , Nitric Oxide Synthase/metabolism , Placenta/blood supply , Amino Acid Transport Systems, Basic/genetics , Biological Transport , Capillaries/cytology , Cells, Cultured , Endothelium, Vascular/enzymology , Fusion Regulatory Protein 1, Heavy Chain/metabolism , Humans , Nitric Oxide Synthase Type III , RNA, Messenger/metabolism , Transcription, Genetic
16.
J Clin Endocrinol Metab ; 88(9): 4287-92, 2003 Sep.
Article in English | MEDLINE | ID: mdl-12970300

ABSTRACT

Cord blood levels of nitrate/nitrite, as a measure of nitric oxide (NO), are generally increased in preeclampsia. As L-arginine is the precursor for NO synthesis, we hypothesized that L-arginine transport across the syncytiotrophoblast basal plasma membrane (BM) of placentas from preeclamptic patients is also increased. Glutamine-sensitive and -insensitive [(3)H]L-arginine uptakes into BM vesicles were measured and expressed as femtomoles per milligram of protein per minute. Total L-arginine uptake was 418 +/- 15 (mean +/- SEM; n = 9) in BM from control placentas (CBM) and 495 +/- 27 (n = 7) in BM from preeclamptic placentas (PE BM; P < 0.05, by two-tailed t test). Glutamine insensitive (system y(+)) uptake was 45 +/- 3 (n = 6) in CBM, with a significantly higher uptake of 97 +/- 23 (n = 5) into PE BM (P < 0.05, by two-tailed t test). There was no significant difference in glutamine-sensitive uptake between the two groups. The expression of mRNA for human cationic amino acid transporter (hCAT) 1, 2, and 4 (system y(+) genes) and 4F2hc (heavy chain of system y(+)L) was not different in homogenates of whole placenta from the two groups. Western blotting data showed that hCAT-1 protein expression in PE BM was higher than that in CBM. These data suggest increased activity of the BM system y(+) cationic amino acid transporter in preeclampsia. If reflected in vivo, a similar increase in transporter activity could alter the delivery of L-arginine to syncytiotrophoblast eNOS.


Subject(s)
Arginine/metabolism , Placenta/metabolism , Pre-Eclampsia/metabolism , Trophoblasts/metabolism , Adult , Alkaline Phosphatase/metabolism , Biological Transport, Active , Blotting, Western , Cationic Amino Acid Transporter 1/biosynthesis , Cell Membrane/metabolism , Densitometry , Female , Humans , In Vitro Techniques , Kinetics , Placenta/cytology , Pre-Eclampsia/pathology , Pregnancy , RNA, Messenger/biosynthesis , Reverse Transcriptase Polymerase Chain Reaction
17.
Arch Dis Child Fetal Neonatal Ed ; 88(3): F237-44, 2003 May.
Article in English | MEDLINE | ID: mdl-12719399

ABSTRACT

BACKGROUND: Childhood leukaemias express novel, clonotypic fusion genes that may already be present at birth before the clinical manifestation of leukaemia. Exposure of the fetus to diagnostic x rays is reported to increase the risk of childhood leukaemia, and may do so by generating leukaemic fusion genes. Advances in neonatal medicine in the past decade that have extended the limits of viability of preterm babies down to 23 weeks of gestation have resulted in the increased use of diagnostic x rays to monitor neonatal progress. AIM: To investigate whether exposure of very preterm infants to diagnostic x rays in the neonatal period leads to the development of leukaemic fusion genes. METHODS: Peripheral blood samples were collected at birth from very preterm infants (23-30 weeks gestation) and following exposure to diagnostic x rays at intervals of two weeks, until discharge. Cord blood samples from normal full term infants served as controls. Total RNA was extracted from the blood and the expression of the fusion genes TEL-AML1, MLL-AF4, and BCR-ABL, characteristic of three subtypes of childhood leukaemia, was investigated in the preterm and full term infant samples using a nested reverse transcriptase polymerase chain reaction method. Serial pre- and post-x ray samples from 42 preterm babies, pre-x ray samples from an additional 46 preterm infants, and cord blood samples from 100 normal full term infants were screened for fusion gene transcripts. RESULTS: No leukaemic fusion gene transcripts were detected in preterm infants following exposure to diagnostic x rays. A BCR-ABL transcript was identified in a single preterm infant prior to x ray exposure. TEL-AML1 transcripts were detected in cord blood samples from two full term infants. MLL-AF4 transcripts were not detected in any of the pre- or full term infants tested. CONCLUSIONS: Exposure of the preterm infants to x rays in this small series and at the doses used for diagnostic purposes did not induce leukaemic fusion gene expression, but we cannot exclude the possibility that a small proportion of preterm infants may be unusually sensitive to x rays.


Subject(s)
Fusion Proteins, bcr-abl/blood , Infant, Premature/blood , Oncogene Proteins, Fusion/blood , Prenatal Diagnosis/adverse effects , X-Rays/adverse effects , Cell Line , Core Binding Factor Alpha 2 Subunit , Female , Gene Amplification , Humans , Infant, Newborn , Leukemia/etiology , Male , Myeloid-Lymphoid Leukemia Protein , RNA/analysis , Radiometry , Reverse Transcriptase Polymerase Chain Reaction/methods
18.
Arch Dis Child Fetal Neonatal Ed ; 86(2): F96-F101, 2002 Mar.
Article in English | MEDLINE | ID: mdl-11882551

ABSTRACT

AIMS: To investigate whether antenatal steroids reduce the incidence of cerebral white matter lesions in very low birthweight infants. METHODS: A total of 224 newborn infants of < 31 weeks gestational age and weighing < 1500 g was studied between January 1998 and June 2000. Obstetric and neonatal information was obtained from the case notes. The study population was subdivided into two groups according to antenatal steroid exposure. A complete course of treatment consisted of two doses of 12 mg each of betamethasone given at an interval of 12-24 hours. Infants in group 1 were born to mothers who had not received betamethasone, or were delivered within 24 hours of receiving the first dose of steroid. Infants in group 2 were born to mothers who had received one or more complete courses of betamethasone and were delivered > 24 hours after receiving the first dose of steroid. RESULTS: The two groups contained statistically similar proportions of boys and girls, and the infants had similar birth weights and survival rates. Those in group 2, compared with those in group 1, had a lower gestational age (p = 0.02) and a lower incidence of white matter lesions on cranial ultrasound scans (p = 0.03). Stepwise logistic regression analysis showed that gestational age (p = 0.0002) and a complete course of antenatal steroids (p = 0.02) had independent effects on cerebral white matter lesions. CONCLUSIONS: These observations suggest that a complete course of antenatal steroids may have a protective effect against cerebral white matter lesions in very low birthweight infants.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Betamethasone/therapeutic use , Brain Diseases/prevention & control , Glucocorticoids/therapeutic use , Infant, Premature, Diseases/prevention & control , Prenatal Care/methods , Analysis of Variance , Female , Gestational Age , Humans , Infant, Newborn , Infant, Premature , Infant, Very Low Birth Weight , Logistic Models , Male , Treatment Outcome
19.
J Clin Endocrinol Metab ; 87(2): 747-51, 2002 Feb.
Article in English | MEDLINE | ID: mdl-11836315

ABSTRACT

Nitric oxide (NO) is an important regulator of placental perfusion, and its production is dependent on the activity of substrate (L-arginine) transporters. In the light of evidence for altered NO production in the feto-placental unit in preeclampsia and intrauterine growth restriction (IUGR), we investigated gestational changes in human placental L-arginine transport by systems y(+) and y(+)L in purified microvillous plasma membrane vesicles. We also examined the effect of preeclampsia and IUGR on the activity of these transport systems and the relationship between transporter activity and NO production (nitrate/nitrite concentrations) in the feto-placental unit. Between first trimester and term, there was a significant positive correlation between system y(+) activity and gestational age (r = 0.36; P = 0.013; n = 47), but a significant negative correlation between system y(+)L activity and gestational age (r = -0.6; P < 0.0001; n = 47). The activity of these transport systems was not altered in preeclampsia or IUGR. In placentas from normal term pregnancies, there was no correlation between the activity of microvillous plasma membrane L-arginine transporters and nitrate/nitrite concentrations in umbilical venous plasma or placental homogenate.


Subject(s)
Arginine/metabolism , Giant Cells/metabolism , Nitric Oxide/biosynthesis , Placenta/physiology , Trophoblasts/metabolism , Biological Transport , Cell Membrane/metabolism , Female , Fetal Growth Retardation/metabolism , Gestational Age , Humans , Microvilli/metabolism , Pre-Eclampsia/metabolism , Pregnancy , Reference Values
20.
Pediatr Res ; 48(6): 821-8, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11102553

ABSTRACT

To test the hypothesis that discordant growth in monochorionic (MC) twins occurs at least in part due to disparity in placental amino acid transporter function, we measured plasma amino acid levels by HPLC in maternal and fetal blood samples collected at birth from gestational age matched twins with (n = 12) and without (n = 12) twin-twin transfusion syndrome (TTTS). In the donor twin, fetal plasma concentrations and feto-maternal ratios of five essential amino acids-valine (p < 0.001), leucine (p < 0.001), iso-leucine (p < 0.05), histidine (p < 0.001) and L-arginine (p < 0. 001)-were lower than the recipient and non-TTTS twin pairs. Fetal concentrations of the nonessential amino acids taurine (p < 0.001), serine (p < 0.01), glycine (p < 0.001) and tyrosine (p < 0.05) were also markedly lower in the donor than the recipient and non-TTTS twin pairs. In contrast, the fetal alanine level in the donor twin was higher than the recipient (664 +/- 64 versus 396 +/- 23 microM; p < 0.001) and the non-TTTS twin pairs (p < 0.01). No such differences between amino acid profiles in non-TTTS MC twin pairs were found. Maternal plasma amino acid levels between TTTS and non-TTTS groups were comparable. This study provides the first evidence that certain amino acids in the donor twin of chronic TTTS differ significantly from those of the co-twin while others were comparable between twin pairs. These data, therefore, argue against inter-twin transfusion as the sole cause of growth restriction of the donor twin and suggests instead that impaired placental transport of amino acids may be a likely mechanism.


Subject(s)
Amino Acids/blood , Diseases in Twins , Fetofetal Transfusion/blood , Twins, Monozygotic , Amino Acids, Essential/metabolism , Birth Weight , Female , Fetal Growth Retardation/etiology , Gestational Age , Humans , Male , Placenta/metabolism , Pregnancy
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