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Sample records for frataxin deficiency reveals

  1. Oxidative stress induces mitochondrial fragmentation in frataxin-deficient cells

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    Lefevre, Sophie [Mitochondria, Metals and Oxidative Stress Laboratory, Institut Jacques Monod, CNRS-Universite Paris-Diderot, Sorbonne Paris Cite, 15 rue Helene Brion, 75205 Paris cedex 13 (France); ED515 UPMC, 4 place Jussieu 75005 Paris (France); Sliwa, Dominika [Mitochondria, Metals and Oxidative Stress Laboratory, Institut Jacques Monod, CNRS-Universite Paris-Diderot, Sorbonne Paris Cite, 15 rue Helene Brion, 75205 Paris cedex 13 (France); Rustin, Pierre [Inserm, U676, Physiopathology and Therapy of Mitochondrial Disease Laboratory, 75019 Paris (France); Universite Paris-Diderot, Faculte de Medecine Denis Diderot, IFR02 Paris (France); Camadro, Jean-Michel [Mitochondria, Metals and Oxidative Stress Laboratory, Institut Jacques Monod, CNRS-Universite Paris-Diderot, Sorbonne Paris Cite, 15 rue Helene Brion, 75205 Paris cedex 13 (France); Santos, Renata, E-mail: santos.renata@ijm.univ-paris-diderot.fr [Mitochondria, Metals and Oxidative Stress Laboratory, Institut Jacques Monod, CNRS-Universite Paris-Diderot, Sorbonne Paris Cite, 15 rue Helene Brion, 75205 Paris cedex 13 (France)

    2012-02-10

    Highlights: Black-Right-Pointing-Pointer Yeast frataxin-deficiency leads to increased proportion of fragmented mitochondria. Black-Right-Pointing-Pointer Oxidative stress induces complete mitochondrial fragmentation in {Delta}yfh1 cells. Black-Right-Pointing-Pointer Oxidative stress increases mitochondrial fragmentation in patient fibroblasts. Black-Right-Pointing-Pointer Inhibition of mitochondrial fission in {Delta}yfh1 induces oxidative stress resistance. -- Abstract: Friedreich ataxia (FA) is the most common recessive neurodegenerative disease. It is caused by deficiency in mitochondrial frataxin, which participates in iron-sulfur cluster assembly. Yeast cells lacking frataxin ({Delta}yfh1 mutant) showed an increased proportion of fragmented mitochondria compared to wild-type. In addition, oxidative stress induced complete fragmentation of mitochondria in {Delta}yfh1 cells. Genetically controlled inhibition of mitochondrial fission in these cells led to increased resistance to oxidative stress. Here we present evidence that in yeast frataxin-deficiency interferes with mitochondrial dynamics, which might therefore be relevant for the pathophysiology of FA.

  2. Mesenchymal Stem Cell-Derived Factors Restore Function to Human Frataxin-Deficient Cells.

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    Kemp, Kevin; Dey, Rimi; Cook, Amelia; Scolding, Neil; Wilkins, Alastair

    2017-08-01

    Friedreich's ataxia is an inherited neurological disorder characterised by mitochondrial dysfunction and increased susceptibility to oxidative stress. At present, no therapy has been shown to reduce disease progression. Strategies being trialled to treat Friedreich's ataxia include drugs that improve mitochondrial function and reduce oxidative injury. In addition, stem cells have been investigated as a potential therapeutic approach. We have used siRNA-induced knockdown of frataxin in SH-SY5Y cells as an in vitro cellular model for Friedreich's ataxia. Knockdown of frataxin protein expression to levels detected in patients with the disorder was achieved, leading to decreased cellular viability, increased susceptibility to hydrogen peroxide-induced oxidative stress, dysregulation of key anti-oxidant molecules and deficiencies in both cell proliferation and differentiation. Bone marrow stem cells are being investigated extensively as potential treatments for a wide range of neurological disorders, including Friedreich's ataxia. The potential neuroprotective effects of bone marrow-derived mesenchymal stem cells were therefore studied using our frataxin-deficient cell model. Soluble factors secreted by mesenchymal stem cells protected against cellular changes induced by frataxin deficiency, leading to restoration in frataxin levels and anti-oxidant defences, improved survival against oxidative stress and stimulated both cell proliferation and differentiation down the Schwann cell lineage. The demonstration that mesenchymal stem cell-derived factors can restore cellular homeostasis and function to frataxin-deficient cells further suggests that they may have potential therapeutic benefits for patients with Friedreich's ataxia.

  3. The yeast metacaspase is implicated in oxidative stress response in frataxin-deficient cells.

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    Lefevre, Sophie; Sliwa, Dominika; Auchère, Françoise; Brossas, Caroline; Ruckenstuhl, Christoph; Boggetto, Nicole; Lesuisse, Emmanuel; Madeo, Frank; Camadro, Jean-Michel; Santos, Renata

    2012-01-20

    Friedreich ataxia is the most common recessive neurodegenerative disease and is caused by reduced expression of mitochondrial frataxin. Frataxin depletion causes impairment in iron-sulfur cluster and heme biosynthesis, disruption of iron homeostasis and hypersensitivity to oxidants. Currently no pharmacological treatment blocks disease progression, although antioxidant therapies proved to benefit patients. We show that sensitivity of yeast frataxin-deficient cells to hydrogen peroxide is partially mediated by the metacaspase. Metacaspase deletion in frataxin-deficient cells results in recovery of antioxidant capacity and heme synthesis. In addition, our results suggest that metacaspase is associated with mitochondrial respiration, intracellular redox control and genomic stability. Copyright © 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  4. A Yeast/Drosophila Screen to Identify New Compounds Overcoming Frataxin Deficiency

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    Alexandra Seguin

    2015-01-01

    Full Text Available Friedreich’s ataxia (FA is a rare neurodegenerative disease which is very debilitating for the patients who progressively lose their autonomy. The lack of efficient therapeutic treatment of the disease strongly argues for urgent need to search for new active compounds that may stop the progression of the disease or prevent the appearance of the symptoms when the genetic defect is diagnosed early enough. In the present study, we used a yeast strain with a deletion of the frataxin homologue gene as a model of FA cells in a primary screen of two chemical libraries, a fraction of the French National Chemical Library (5500 compounds and the Prestwick collection (880 compounds. We ran a secondary screen on Drosophila melanogaster flies expressing reduced levels of frataxin during larval development. Half of the compounds selected in yeast appeared to be active in flies in this developmental paradigm, and one of the two compounds with highest activities in this assay partially rescued the heart dilatation phenotype resulting from heart specific depletion of frataxin. The unique complementarity of these two frataxin-deficient models, unicellular and multicellular, appears to be very efficient to select new compounds with improved selectivity, bringing significant perspectives towards improvements in FA therapy.

  5. Mitochondrial localization of human frataxin is necessary but processing is not for rescuing frataxin deficiency in Trypanosoma brucei

    Czech Academy of Sciences Publication Activity Database

    Long, Shaojun; Jirků, Milan; Ayala, F. J.; Lukeš, Julius

    2008-01-01

    Roč. 105, č. 36 (2008), s. 13468-13473 ISSN 0027-8424 R&D Projects: GA AV ČR IAA500960705; GA MŠk LC07032; GA MŠk 2B06129; GA ČR GA204/06/1558 Institutional research plan: CEZ:AV0Z60220518 Keywords : frataxin * mitochondrion * Trypanosoma * Kinetoplastida Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 9.380, year: 2008

  6. Mitochondrial dysfunction induced by frataxin deficiency is associated with cellular senescence and abnormal calcium metabolism

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    Arantxa eBolinches-Amorós

    2014-05-01

    Full Text Available Friedreich ataxia is considered a neurodegenerative disorder involving both the peripheral and central nervous systems. Dorsal root ganglia (DRG are the major target tissue structures. This neuropathy is caused by mutations in the FXN gene that encodes frataxin. Here, we investigated the mitochondrial and cell consequences of frataxin depletion in a cellular model based on frataxin silencing in SH-SY5Y human neuroblastoma cells, a cell line that has been used widely as in vitro models for studies on neurological diseases. We showed that the reduction of frataxin induced mitochondrial dysfunction due to a bioenergetic deficit and abnormal Ca2+ homeostasis in the mitochondria that were associated with oxidative and endoplasmic reticulum stresses. The depletion of frataxin did not cause cell death but increased autophagy, which may have a cytoprotective effect against cellular insults such as oxidative stress. Frataxin silencing provoked slow cell growth associated with cellular senescence, as demonstrated by increased SA-βgal activity and cell cycle arrest at the G1 phase. We postulate that cellular senescence might be related to a hypoplastic defect in the DRG during neurodevelopment, as suggested by necropsy studies.

  7. Reversible Axonal Dystrophy by Calcium Modulation in Frataxin-Deficient Sensory Neurons of YG8R Mice

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    Belén Mollá

    2017-08-01

    Full Text Available Friedreich’s ataxia (FRDA is a peripheral neuropathy involving a loss of proprioceptive sensory neurons. Studies of biopsies from patients suggest that axonal dysfunction precedes the death of proprioceptive neurons in a dying-back process. We observed that the deficiency of frataxin in sensory neurons of dorsal root ganglia (DRG of the YG8R mouse model causes the formation of axonal spheroids which retain dysfunctional mitochondria, shows alterations in the cytoskeleton and it produces impairment of axonal transport and autophagic flux. The homogenous distribution of axonal spheroids along the neurites supports the existence of continues focal damages. This lead us to propose for FRDA a model of distal axonopathy based on axonal focal damages. In addition, we observed the involvement of oxidative stress and dyshomeostasis of calcium in axonal spheroid formation generating axonal injury as a primary cause of pathophysiology. Axonal spheroids may be a consequence of calcium imbalance, thus we propose the quenching or removal extracellular Ca2+ to prevent spheroids formation. In our neuronal model, treatments with BAPTA and o-phenanthroline reverted the axonal dystrophy and the mitochondrial dysmorphic parameters. These results support the hypothesis that axonal pathology is reversible in FRDA by pharmacological manipulation of intracellular Ca2+ with Ca2+ chelators or metalloprotease inhibitors, preventing Ca2+-mediated axonal injury. Thus, the modulation of Ca2+ levels may be a relevant therapeutic target to develop early axonal protection and prevent dying-back neurodegeneration.

  8. Time-resolved functional analysis of acute impairment of frataxin expression in an inducible cell model of Friedreich ataxia

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    Dörte Poburski

    2016-05-01

    Full Text Available Friedreich ataxia is a neurodegenerative disease caused by a GAA triplet repeat expansion in the first intron of the frataxin gene, which results in reduced expression levels of the corresponding protein. Despite numerous animal and cellular models, therapeutic options that mechanistically address impaired frataxin expression are lacking. Here, we have developed a new mammalian cell model employing the Cre/loxP recombination system to induce a homozygous or heterozygous frataxin knockout in mouse embryonic fibroblasts. Induction of Cre-mediated disruption by tamoxifen was successfully tested on RNA and protein levels. After loss of frataxin protein, cell division, aconitase activity and oxygen consumption rates were found to be decreased, while ROS production was increased in the homozygous state. By contrast, in the heterozygous state no such changes were observed. A time-resolved analysis revealed the loss of aconitase activity as an initial event after induction of complete frataxin deficiency, followed by secondarily elevated ROS production and a late increase in iron content. Initial impairments of oxygen consumption and ATP production were found to be compensated in the late state and seemed to play a minor role in Friedreich ataxia pathophysiology. In conclusion and as predicted from its proposed role in iron sulfur cluster (ISC biosynthesis, disruption of frataxin primarily causes impaired function of ISC-containing enzymes, whereas other consequences, including elevated ROS production and iron accumulation, appear secondary. These parameters and the robustness of the newly established system may additionally be used for a time-resolved study of pharmacological candidates in a HTS manner.

  9. Mesenchymal stem cells restore frataxin expression and increase hydrogen peroxide scavenging enzymes in Friedreich ataxia fibroblasts.

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    Kevin Kemp

    Full Text Available Dramatic advances in recent decades in understanding the genetics of Friedreich ataxia (FRDA--a GAA triplet expansion causing greatly reduced expression of the mitochondrial protein frataxin--have thus far yielded no therapeutic dividend, since there remain no effective treatments that prevent or even slow the inevitable progressive disability in affected individuals. Clinical interventions that restore frataxin expression are attractive therapeutic approaches, as, in theory, it may be possible to re-establish normal function in frataxin deficient cells if frataxin levels are increased above a specific threshold. With this in mind several drugs and cytokines have been tested for their ability to increase frataxin levels. Cell transplantation strategies may provide an alternative approach to this therapeutic aim, and may also offer more widespread cellular protective roles in FRDA. Here we show a direct link between frataxin expression in fibroblasts derived from FRDA patients with both decreased expression of hydrogen peroxide scavenging enzymes and increased sensitivity to hydrogen peroxide-mediated toxicity. We demonstrate that normal human mesenchymal stem cells (MSCs induce both an increase in frataxin gene and protein expression in FRDA fibroblasts via secretion of soluble factors. Finally, we show that exposure to factors produced by human MSCs increases resistance to hydrogen peroxide-mediated toxicity in FRDA fibroblasts through, at least in part, restoring the expression of the hydrogen peroxide scavenging enzymes catalase and glutathione peroxidase 1. These findings suggest, for the first time, that stem cells may increase frataxin levels in FRDA and transplantation of MSCs may offer an effective treatment for these patients.

  10. Frataxin Is Localized to Both the Chloroplast and Mitochondrion and Is Involved in Chloroplast Fe-S Protein Function in Arabidopsis.

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    Valeria R Turowski

    Full Text Available Frataxin plays a key role in eukaryotic cellular iron metabolism, particularly in mitochondrial heme and iron-sulfur (Fe-S cluster biosynthesis. However, its precise role has yet to be elucidated. In this work, we studied the subcellular localization of Arabidopsis frataxin, AtFH, using confocal microscopy, and found a novel dual localization for this protein. We demonstrate that plant frataxin is targeted to both the mitochondria and the chloroplast, where it may play a role in Fe-S cluster metabolism as suggested by functional studies on nitrite reductase (NIR and ferredoxin (Fd, two Fe-S containing chloroplast proteins, in AtFH deficient plants. Our results indicate that frataxin deficiency alters the normal functioning of chloroplasts by affecting the levels of Fe, chlorophyll, and the photosynthetic electron transport chain in this organelle.

  11. Turning Escherichia coli into a Frataxin-Dependent Organism.

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    Béatrice Roche

    2015-05-01

    Full Text Available Fe-S bound proteins are ubiquitous and contribute to most basic cellular processes. A defect in the ISC components catalyzing Fe-S cluster biogenesis leads to drastic phenotypes in both eukaryotes and prokaryotes. In this context, the Frataxin protein (FXN stands out as an exception. In eukaryotes, a defect in FXN results in severe defects in Fe-S cluster biogenesis, and in humans, this is associated with Friedreich's ataxia, a neurodegenerative disease. In contrast, prokaryotes deficient in the FXN homolog CyaY are fully viable, despite the clear involvement of CyaY in ISC-catalyzed Fe-S cluster formation. The molecular basis of the differing importance in the contribution of FXN remains enigmatic. Here, we have demonstrated that a single mutation in the scaffold protein IscU rendered E. coli viability strictly dependent upon a functional CyaY. Remarkably, this mutation changed an Ile residue, conserved in prokaryotes at position 108, into a Met residue, conserved in eukaryotes. We found that in the double mutant IscUIM ΔcyaY, the ISC pathway was completely abolished, becoming equivalent to the ΔiscU deletion strain and recapitulating the drastic phenotype caused by FXN deletion in eukaryotes. Biochemical analyses of the "eukaryotic-like" IscUIM scaffold revealed that it exhibited a reduced capacity to form Fe-S clusters. Finally, bioinformatic studies of prokaryotic IscU proteins allowed us to trace back the source of FXN-dependency as it occurs in present-day eukaryotes. We propose an evolutionary scenario in which the current mitochondrial Isu proteins originated from the IscUIM version present in the ancestor of the Rickettsiae. Subsequent acquisition of SUF, the second Fe-S cluster biogenesis system, in bacteria, was accompanied by diminished contribution of CyaY in prokaryotic Fe-S cluster biogenesis, and increased tolerance to change in the amino acid present at the 108th position of the scaffold.

  12. Monomeric Yeast Frataxin is an Iron-Binding Protein

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    Cook, J.; Bencze, K.; Jankovic, A.; Crater, A.; Busch, C.; Bradley, P.; Stemmler, A.; Spaller, M.; Stemmler, T.

    2006-01-01

    Friedreich's ataxia, an autosomal cardio- and neurodegenerative disorder that affects 1 in 50 000 humans, is caused by decreased levels of the protein frataxin. Although frataxin is nuclear-encoded, it is targeted to the mitochondrial matrix and necessary for proper regulation of cellular iron homeostasis. Frataxin is required for the cellular production of both heme and iron-sulfur (Fe-S) clusters. Monomeric frataxin binds with high affinity to ferrochelatase, the enzyme involved in iron insertion into porphyrin during heme production. Monomeric frataxin also binds to Isu, the scaffold protein required for assembly of Fe-S cluster intermediates. These processes (heme and Fe-S cluster assembly) share requirements for iron, suggesting that monomeric frataxin might function as the common iron donor. To provide a molecular basis to better understand frataxin's function, we have characterized the binding properties and metal-site structure of ferrous iron bound to monomeric yeast frataxin. Yeast frataxin is stable as an iron-loaded monomer, and the protein can bind two ferrous iron atoms with micromolar binding affinity. Frataxin amino acids affected by the presence of iron are localized within conserved acidic patches located on the surfaces of both helix-1 and strand-1. Under anaerobic conditions, bound metal is stable in the high-spin ferrous state. The metal-ligand coordination geometry of both metal-binding sites is consistent with a six-coordinate iron-(oxygen/nitrogen) based ligand geometry, surely constructed in part from carboxylate and possibly imidazole side chains coming from residues within these conserved acidic patches on the protein. On the basis of our results, we have developed a model for how we believe yeast frataxin interacts with iron

  13. Novel frataxin isoforms may contribute to the pathological mechanism of Friedreich ataxia.

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    Haiyan Xia

    Full Text Available Friedreich ataxia (FRDA is an inherited neurodegenerative disease caused by frataxin (FXN deficiency. The nervous system and heart are the most severely affected tissues. However, highly mitochondria-dependent tissues, such as kidney and liver, are not obviously affected, although the abundance of FXN is normally high in these tissues. In this study we have revealed two novel FXN isoforms (II and III, which are specifically expressed in affected cerebellum and heart tissues, respectively, and are functional in vitro and in vivo. Increasing the abundance of the heart-specific isoform III significantly increased the mitochondrial aconitase activity, while over-expression of the cerebellum-specific isoform II protected against oxidative damage of Fe-S cluster-containing aconitase. Further, we observed that the protein level of isoform III decreased in FRDA patient heart, while the mRNA level of isoform II decreased more in FRDA patient cerebellum compared to total FXN mRNA. Our novel findings are highly relevant to understanding the mechanism of tissue-specific pathology in FRDA.

  14. Frataxin mRNA Isoforms in FRDA Patients and Normal Subjects: Effect of Tocotrienol Supplementation

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    Provvidenza Maria Abruzzo

    2013-01-01

    Full Text Available Friedreich’s ataxia (FRDA is caused by deficient expression of the mitochondrial protein frataxin involved in the formation of iron-sulphur complexes and by consequent oxidative stress. We analysed low-dose tocotrienol supplementation effects on the expression of the three splice variant isoforms (FXN-1, FXN-2, and FXN-3 in mononuclear blood cells of FRDA patients and healthy subjects. In FRDA patients, tocotrienol leads to a specific and significant increase of FXN-3 expression while not affecting FXN-1 and FXN-2 expression. Since no structural and functional details were available for FNX-2 and FXN-3, 3D models were built. FXN-1, the canonical isoform, was then docked on the human iron-sulphur complex, and functional interactions were computed; when FXN-1 was replaced by FXN-2 or FNX-3, we found that the interactions were maintained, thus suggesting a possible biological role for both isoforms in human cells. Finally, in order to evaluate whether tocotrienol enhancement of FXN-3 was mediated by an increase in peroxisome proliferator-activated receptor-γ (PPARG, PPARG expression was evaluated. At a low dose of tocotrienol, the increase of FXN-3 expression appeared to be independent of PPARG expression. Our data show that it is possible to modulate the mRNA expression of the minor frataxin isoforms and that they may have a functional role.

  15. Overexpression of human and fly frataxins in Drosophila provokes deleterious effects at biochemical, physiological and developmental levels.

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    Juan A Navarro

    Full Text Available BACKGROUND: Friedreich's ataxia (FA, the most frequent form of inherited ataxias in the Caucasian population, is caused by a reduced expression of frataxin, a highly conserved protein. Model organisms have contributed greatly in the efforts to decipher the function of frataxin; however, the precise function of this protein remains elusive. Overexpression studies are a useful approach to investigate the mechanistic actions of frataxin; however, the existing literature reports contradictory results. To further investigate the effect of frataxin overexpression, we analyzed the consequences of overexpressing human (FXN and fly (FH frataxins in Drosophila. METHODOLOGY/PRINCIPAL FINDINGS: We obtained transgenic flies that overexpressed human or fly frataxins in a general pattern and in different tissues using the UAS-GAL4 system. For both frataxins, we observed deleterious effects at the biochemical, histological and behavioral levels. Oxidative stress is a relevant factor in the frataxin overexpression phenotypes. Systemic frataxin overexpression reduces Drosophila viability and impairs the normal embryonic development of muscle and the peripheral nervous system. A reduction in the level of aconitase activity and a decrease in the level of NDUF3 were also observed in the transgenic flies that overexpressed frataxin. Frataxin overexpression in the nervous system reduces life span, impairs locomotor ability and causes brain degeneration. Frataxin aggregation and a misfolding of this protein have been shown not to be the mechanism that is responsible for the phenotypes that have been observed. Nevertheless, the expression of human frataxin rescues the aconitase activity in the fh knockdown mutant. CONCLUSION/SIGNIFICANCE: Our results provide in vivo evidence of a functional equivalence for human and fly frataxins and indicate that the control of frataxin expression is important for treatments that aim to increase frataxin levels.

  16. Ancestral roles of eukaryotic frataxin: mitochondrial frataxin function and heterologous expression of hydrogenosomal Trichomonas homologs in trypanosomes

    Czech Academy of Sciences Publication Activity Database

    Long, Shaojun; Jirků, Milan; Mach, J.; Ginger, M. L.; Sutak, R.; Richardson, D.; Tachezy, J.; Lukeš, Julius

    2008-01-01

    Roč. 69, č. 1 (2008), s. 94-109 ISSN 0950-382X R&D Projects: GA AV ČR IAA500960705; GA MŠk LC07032; GA MŠk 2B06129; GA ČR GA204/06/1558 Institutional research plan: CEZ:AV0Z60220518 Keywords : frataxin * mitochondrion * Trypanosoma * Fe-S clusters * Trichomonas Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.213, year: 2008

  17. Overexpression of Drosophila frataxin triggers cell death in an iron-dependent manner.

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    Edenharter, Oliver; Clement, Janik; Schneuwly, Stephan; Navarro, Juan A

    2017-12-01

    Friedreich ataxia (FRDA) is the most important autosomal recessive ataxia in the Caucasian population. FRDA patients display severe neurological and cardiac symptoms that reflect a strong cellular and axonal degeneration. FRDA is caused by a loss of function of the mitochondrial protein frataxin which impairs the biosynthesis of iron-sulfur clusters and in turn the catalytic activity of several enzymes in the Krebs cycle and the respiratory chain leading to a diminished energy production. Although FRDA is due to frataxin depletion, overexpression might also be very helpful to better understand cellular functions of frataxin. In this work, we have increased frataxin expression in neurons to elucidate specific roles that frataxin might play in these tissues. Using molecular, biochemical, histological and behavioral methods, we report that frataxin overexpression is sufficient to increase oxidative phosphorylation, modify mitochondrial morphology, alter iron homeostasis and trigger oxidative stress-dependent cell death. Interestingly, genetic manipulation of mitochondrial iron metabolism by silencing mitoferrin successfully improves cell survival under oxidative-attack conditions, although enhancing antioxidant defenses or mitochondrial fusion failed to ameliorate frataxin overexpression phenotypes. This result suggests that cell degeneration is directly related to enhanced incorporation of iron into the mitochondria. Drosophila frataxin overexpression might also provide an alternative approach to identify processes that are important in FRDA such as changes in mitochondrial morphology and oxidative stress induced cell death.

  18. Metabolomics Approach Reveals Integrated Metabolic Network Associated with Serotonin Deficiency

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    Weng, Rui; Shen, Sensen; Tian, Yonglu; Burton, Casey; Xu, Xinyuan; Liu, Yi; Chang, Cuilan; Bai, Yu; Liu, Huwei

    2015-07-01

    Serotonin is an important neurotransmitter that broadly participates in various biological processes. While serotonin deficiency has been associated with multiple pathological conditions such as depression, schizophrenia, Alzheimer’s disease and Parkinson’s disease, the serotonin-dependent mechanisms remain poorly understood. This study therefore aimed to identify novel biomarkers and metabolic pathways perturbed by serotonin deficiency using metabolomics approach in order to gain new metabolic insights into the serotonin deficiency-related molecular mechanisms. Serotonin deficiency was achieved through pharmacological inhibition of tryptophan hydroxylase (Tph) using p-chlorophenylalanine (pCPA) or genetic knockout of the neuronal specific Tph2 isoform. This dual approach improved specificity for the serotonin deficiency-associated biomarkers while minimizing nonspecific effects of pCPA treatment or Tph2 knockout (Tph2-/-). Non-targeted metabolic profiling and a targeted pCPA dose-response study identified 21 biomarkers in the pCPA-treated mice while 17 metabolites in the Tph2-/- mice were found to be significantly altered compared with the control mice. These newly identified biomarkers were associated with amino acid, energy, purine, lipid and gut microflora metabolisms. Oxidative stress was also found to be significantly increased in the serotonin deficient mice. These new biomarkers and the overall metabolic pathways may provide new understanding for the serotonin deficiency-associated mechanisms under multiple pathological states.

  19. Identification of two frataxin isoforms in Zea mays: Structural and functional studies.

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    Buchensky, Celeste; Sánchez, Manuel; Carrillo, Martin; Palacios, Oscar; Capdevila, Mercè; Domínguez-Vera, Jose M; Busi, Maria V; Atrian, Sílvia; Pagani, Maria A; Gomez-Casati, Diego F

    2017-09-01

    Frataxin is a ubiquitous protein that plays a role in Fe-S cluster biosynthesis and iron and heme metabolism, although its molecular functions are not entirely clear. In non-photosynthetic eukaryotes, frataxin is encoded by a single gene, and the protein localizes to mitochondria. Here we report the presence of two functional frataxin isoforms in Zea mays, ZmFH-1 and ZmFH-2. We confirmed our previous findings regarding plant frataxins: both proteins have dual localization in mitochondria and chloroplasts. Physiological, biochemical and biophysical studies show some differences in the expression pattern, protection against oxidants and in the aggregation state of both isoforms, suggesting that the two frataxin homologs would play similar but not identical roles in plant cell metabolism. In addition, two specific features of plant frataxins were evidenced: their ability to form dimers and their tendency to undergo conformational change under oxygen exposure. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  20. Selected missense mutations impair frataxin processing in Friedreich ataxia.

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    Clark, Elisia; Butler, Jill S; Isaacs, Charles J; Napierala, Marek; Lynch, David R

    2017-08-01

    Frataxin (FXN) is a highly conserved mitochondrial protein. Reduced FXN levels cause Friedreich ataxia, a recessive neurodegenerative disease. Typical patients carry GAA repeat expansions on both alleles, while a subgroup of patients carry a missense mutation on one allele and a GAA repeat expansion on the other. Here, we report that selected disease-related FXN missense mutations impair FXN localization, interaction with mitochondria processing peptidase, and processing. Immunocytochemical studies and subcellular fractionation were performed to study FXN import into the mitochondria and examine the mechanism by which mutations impair FXN processing. Coimmunoprecipitation was performed to study the interaction between FXN and mitochondrial processing peptidase. A proteasome inhibitor was used to model traditional therapeutic strategies. In addition, clinical profiles of subjects with and without point mutations were compared in a large natural history study. FXN I 154F and FXN G 130V missense mutations decrease FXN 81-210 levels compared with FXN WT , FXN R 165C , and FXN W 155R , but do not block its association with mitochondria. FXN I 154F and FXN G 130V also impair FXN maturation and enhance the binding between FXN 42-210 and mitochondria processing peptidase. Furthermore, blocking proteosomal degradation does not increase FXN 81-210 levels. Additionally, impaired FXN processing also occurs in fibroblasts from patients with FXN G 130V . Finally, clinical data from patients with FXN G 130V and FXN I 154F mutations demonstrates a lower severity compared with other individuals with Friedreich ataxia. These data suggest that the effects on processing associated with FXN G 130V and FXN I 154F mutations lead to higher levels of partially processed FXN, which may contribute to the milder clinical phenotypes in these patients.

  1. Mcph1-deficient mice reveal a role for MCPH1 in otitis media.

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    Jing Chen

    Full Text Available Otitis media is a common reason for hearing loss, especially in children. Otitis media is a multifactorial disease and environmental factors, anatomic dysmorphology and genetic predisposition can all contribute to its pathogenesis. However, the reasons for the variable susceptibility to otitis media are elusive. MCPH1 mutations cause primary microcephaly in humans. So far, no hearing impairment has been reported either in the MCPH1 patients or mouse models with Mcph1 deficiency. In this study, Mcph1-deficient (Mcph1(tm1a (/tm1a mice were produced using embryonic stem cells with a targeted mutation by the Sanger Institute's Mouse Genetics Project. Auditory brainstem response measurements revealed that Mcph1(tm1a (/tm1a mice had mild to moderate hearing impairment with around 70% penetrance. We found otitis media with effusion in the hearing-impaired Mcph1(tm1a (/tm1a mice by anatomic and histological examinations. Expression of Mcph1 in the epithelial cells of middle ear cavities supported its involvement in the development of otitis media. Other defects of Mcph1(tm1a (/tm1a mice included small skull sizes, increased micronuclei in red blood cells, increased B cells and ocular abnormalities. These findings not only recapitulated the defects found in other Mcph1-deficient mice or MCPH1 patients, but also revealed an unexpected phenotype, otitis media with hearing impairment, which suggests Mcph1 is a new gene underlying genetic predisposition to otitis media.

  2. Phenolic Profiling of Caffeic Acid O-Methyltransferase-Deficient Poplar Reveals Novel Benzodioxane Oligolignols1

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    Morreel, Kris; Ralph, John; Lu, Fachuang; Goeminne, Geert; Busson, Roger; Herdewijn, Piet; Goeman, Jan L.; Van der Eycken, Johan; Boerjan, Wout; Messens, Eric

    2004-01-01

    Caffeic acid O-methyltransferase (COMT) catalyzes preferentially the methylation of 5-hydroxyconiferaldehyde to sinapaldehyde in monolignol biosynthesis. Here, we have compared HPLC profiles of the methanol-soluble phenolics fraction of xylem tissue from COMT-deficient and control poplars (Populus spp.), using statistical analysis of the peak heights. COMT down-regulation results in significant concentration differences for 25 of the 91 analyzed peaks. Eight peaks were exclusively detected in COMT-deficient poplar, of which four could be purified for further identification using mass spectrometry/mass spectrometry, nuclear magnetic resonance, and spiking of synthesized reference compounds. These new compounds were derived from 5-hydroxyconiferyl alcohol or 5-hydroxyconiferaldehyde and were characterized by benzodioxane moieties, a structural type that is also increased in the lignins of COMT-deficient plants. One of these four benzodioxanes amounted to the most abundant oligolignol in the HPLC profile. Furthermore, all of the differentially accumulating oligolignols involving sinapyl units were either reduced in abundance or undetectable. The concentration levels of all identified oligolignols were in agreement with the relative supply of monolignols and with their chemical coupling propensities, which supports the random coupling hypothesis. Chiral HPLC analysis of the most abundant benzodioxane dimer revealed the presence of both enantiomers in equal amounts, indicating that they were formed by radical coupling reactions under simple chemical control rather than guided by dirigent proteins. PMID:15563622

  3. Phenolic profiling of caffeic acid O-methyltransferase-deficient poplar reveals novel benzodioxane oligolignols.

    Science.gov (United States)

    Morreel, Kris; Ralph, John; Lu, Fachuang; Goeminne, Geert; Busson, Roger; Herdewijn, Piet; Goeman, Jan L; Van der Eycken, Johan; Boerjan, Wout; Messens, Eric

    2004-12-01

    Caffeic acid O-methyltransferase (COMT) catalyzes preferentially the methylation of 5-hydroxyconiferaldehyde to sinapaldehyde in monolignol biosynthesis. Here, we have compared HPLC profiles of the methanol-soluble phenolics fraction of xylem tissue from COMT-deficient and control poplars (Populus spp.), using statistical analysis of the peak heights. COMT down-regulation results in significant concentration differences for 25 of the 91 analyzed peaks. Eight peaks were exclusively detected in COMT-deficient poplar, of which four could be purified for further identification using mass spectrometry/mass spectrometry, nuclear magnetic resonance, and spiking of synthesized reference compounds. These new compounds were derived from 5-hydroxyconiferyl alcohol or 5-hydroxyconiferaldehyde and were characterized by benzodioxane moieties, a structural type that is also increased in the lignins of COMT-deficient plants. One of these four benzodioxanes amounted to the most abundant oligolignol in the HPLC profile. Furthermore, all of the differentially accumulating oligolignols involving sinapyl units were either reduced in abundance or undetectable. The concentration levels of all identified oligolignols were in agreement with the relative supply of monolignols and with their chemical coupling propensities, which supports the random coupling hypothesis. Chiral HPLC analysis of the most abundant benzodioxane dimer revealed the presence of both enantiomers in equal amounts, indicating that they were formed by radical coupling reactions under simple chemical control rather than guided by dirigent proteins.

  4. A Comprehensive Genomic Analysis Reveals the Genetic Landscape of Mitochondrial Respiratory Chain Complex Deficiencies.

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    Masakazu Kohda

    2016-01-01

    Full Text Available Mitochondrial disorders have the highest incidence among congenital metabolic disorders characterized by biochemical respiratory chain complex deficiencies. It occurs at a rate of 1 in 5,000 births, and has phenotypic and genetic heterogeneity. Mutations in about 1,500 nuclear encoded mitochondrial proteins may cause mitochondrial dysfunction of energy production and mitochondrial disorders. More than 250 genes that cause mitochondrial disorders have been reported to date. However exact genetic diagnosis for patients still remained largely unknown. To reveal this heterogeneity, we performed comprehensive genomic analyses for 142 patients with childhood-onset mitochondrial respiratory chain complex deficiencies. The approach includes whole mtDNA and exome analyses using high-throughput sequencing, and chromosomal aberration analyses using high-density oligonucleotide arrays. We identified 37 novel mutations in known mitochondrial disease genes and 3 mitochondria-related genes (MRPS23, QRSL1, and PNPLA4 as novel causative genes. We also identified 2 genes known to cause monogenic diseases (MECP2 and TNNI3 and 3 chromosomal aberrations (6q24.3-q25.1, 17p12, and 22q11.21 as causes in this cohort. Our approaches enhance the ability to identify pathogenic gene mutations in patients with biochemically defined mitochondrial respiratory chain complex deficiencies in clinical settings. They also underscore clinical and genetic heterogeneity and will improve patient care of this complex disorder.

  5. The import and function of diatom and plant frataxins in the mitochondrion of Trypanosoma brucei

    Czech Academy of Sciences Publication Activity Database

    Long, Shaojun; Vávrová, Zuzana; Lukeš, Julius

    2008-01-01

    Roč. 162, č. 1 (2008), s. 100-104 ISSN 0166-6851 R&D Projects: GA AV ČR IAA500960705; GA MŠk LC07032; GA MŠk 2B06129; GA ČR GA204/06/1558 Institutional research plan: CEZ:AV0Z60220518 Keywords : frataxin * mitochondrion * Trypanosoma * diatom * evolutionary conservativeness * import Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.951, year: 2008

  6. SAXS and stability studies of iron-induced oligomers of bacterial frataxin CyaY.

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    Mostafa Fekry

    Full Text Available Frataxin is a highly conserved protein found in both prokaryotes and eukaryotes. It is involved in several central functions in cells, which include iron delivery to biochemical processes, such as heme synthesis, assembly of iron-sulfur clusters (ISC, storage of surplus iron in conditions of iron overload, and repair of ISC in aconitase. Frataxin from different organisms has been shown to undergo iron-dependent oligomerization. At least two different classes of oligomers, with different modes of oligomer packing and stabilization, have been identified. Here, we continue our efforts to explore the factors that control the oligomerization of frataxin from different organisms, and focus on E. coli frataxin CyaY. Using small-angle X-ray scattering (SAXS, we show that higher iron-to-protein ratios lead to larger oligomeric species, and that oligomerization proceeds in a linear fashion as a results of iron oxidation. Native mass spectrometry and online size-exclusion chromatography combined with SAXS show that a dimer is the most common form of CyaY in the presence of iron at atmospheric conditions. Modeling of the dimer using the SAXS data confirms the earlier proposed head-to-tail packing arrangement of monomers. This packing mode brings several conserved acidic residues into close proximity to each other, creating an environment for metal ion binding and possibly even mineralization. Together with negative-stain electron microscopy, the experiments also show that trimers, tetramers, pentamers, and presumably higher-order oligomers may exist in solution. Nano-differential scanning fluorimetry shows that the oligomers have limited stability and may easily dissociate at elevated temperatures. The factors affecting the possible oligomerization mode are discussed.

  7. Redetermination of AgNb2PS10 revealing a silver deficiency

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    Hoseop Yun

    2009-08-01

    Full Text Available In comparison with a previous crystallographic study [Goh et al. (2002. J. Solid State Chem. 168, 119–125] of the title compound, silver diniobium tris(disulfide tetrathiophosphate(V, that reports a full occupation of the silver position and isotropic displacement parameters for the atoms, the current redetermination reveals a silver deficiency with a site-occupation factor of 0.88 (1 and reports all atoms with anisotropic displacement parameters. The structure of Ag0.88Nb2PS10 is composed of ∞1[Nb2PS10] chains, which are built up from pairs of distorted bicapped trigonal-prismatic [NbS8] polyhedra forming [Nb2S12] dimers and of tetrahedral [PS4] groups. These chains are connected via the statistically disordered Ag+ ions, forming double layers. Adjacent layers are stacked solely through van der Waals forces into a three-dimensional structure. Short and long Nb—Nb distances [2.880 (1 and 3.770 (2 Å, respectively] alternate along the chain and S22− and S2− anionic species are observed.

  8. de Toni-Fanconi-Debré syndrome with Leigh syndrome revealing severe muscle cytochrome c oxidase deficiency

    NARCIS (Netherlands)

    Ogier, H.; Lombes, A.; Scholte, H. R.; Poll-The, B. T.; Fardeau, M.; Alcardi, J.; Vignes, B.; Niaudet, P.; Saudubray, J. M.

    1988-01-01

    We describe a patient with severe muscle cytochrome c oxidase deficiency who had de Toni-Fanconi-Debré syndrome and acute neurologic deterioration resembling Leigh syndrome, without clear evidence of muscle abnormality. Metabolic investigations revealed elevated cerebrospinal fluid lactate values

  9. Effects of the deletion of the Escherichia coli frataxin homologue CyaY on the respiratory NADH:ubiquinone oxidoreductase

    Directory of Open Access Journals (Sweden)

    Grauman Peter L

    2007-07-01

    Full Text Available Abstract Background Frataxin is discussed as involved in the biogenesis of iron-sulfur clusters. Recently it was discovered that a frataxin homologue is a structural component of the respiratory NADH:ubiquinone oxidoreductase (complex I in Thermus thermophilus. It was not clear whether frataxin is in general a component of complex I from bacteria. The Escherichia coli homologue of frataxin is coined CyaY. Results We report that complex I is completely assembled to a stable and active enzyme complex equipped with all known iron-sulfur clusters in a cyaY mutant of E. coli. However, the amount of complex I is reduced by one third compared to the parental strain. Western blot analysis and live cell imaging of CyaY engineered with a GFP demonstrated that CyaY is located in the cytoplasm and not attached to the membrane as to be expected if it were a component of complex I. Conclusion CyaY plays a non-essential role in the assembly of complex I in E. coli. It is not a structural component but may transiently interact with the complex.

  10. Diagnosis of adenylosuccinate lyase deficiency by metabolomic profiling in plasma reveals a phenotypic spectrum

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    Taraka R. Donti

    2016-09-01

    Full Text Available Adenylosuccinate lyase (ADSL deficiency is a rare autosomal recessive neurometabolic disorder that presents with a broad-spectrum of neurological and physiological symptoms. The ADSL gene produces an enzyme with binary molecular roles in de novo purine synthesis and purine nucleotide recycling. The biochemical phenotype of ADSL deficiency, accumulation of SAICAr and succinyladenosine (S-Ado in biofluids of affected individuals, serves as the traditional target for diagnosis with targeted quantitative urine purine analysis employed as the predominate method of detection. In this study, we report the diagnosis of ADSL deficiency using an alternative method, untargeted metabolomic profiling, an analytical scheme capable of generating semi-quantitative z-score values for over 1000 unique compounds in a single analysis of a specimen. Using this method to analyze plasma, we diagnosed ADSL deficiency in four patients and confirmed these findings with targeted quantitative biochemical analysis and molecular genetic testing. ADSL deficiency is part of a large a group of neurometabolic disorders, with a wide range of severity and sharing a broad differential diagnosis. This phenotypic similarity among these many inborn errors of metabolism (IEMs has classically stood as a hurdle in their initial diagnosis and subsequent treatment. The findings presented here demonstrate the clinical utility of metabolomic profiling in the diagnosis of ADSL deficiency and highlights the potential of this technology in the diagnostic evaluation of individuals with neurologic phenotypes.

  11. An AAV9 coding for frataxin clearly improved the symptoms and prolonged the life of Friedreich ataxia mouse models

    Directory of Open Access Journals (Sweden)

    Catherine Gérard

    2014-01-01

    Full Text Available Friedreich ataxia (FRDA is a genetic disease due to increased repeats of the GAA trinucleotide in intron 1 of the frataxin gene. This mutation leads to a reduced expression of frataxin. We have produced an adeno-associated virus (AAV9 coding for human frataxin (AAV9-hFXN. This AAV was delivered by intraperitoneal (IP injection to young conditionally knockout mice in which the frataxin gene had been knocked-out in some tissues during embryogenesis by breeding them with mice expressing the Cre recombinase gene under the muscle creatine kinase (MCK or the neuron-specific enolase (NSE promoter. In the first part of the study, different doses of virus were tested from 6 × 1011 v.p. to 6 × 109 v.p. in NSE-cre mice and all leading to an increase in life spent of the mice. The higher and the lower dose were also tested in MCK-cre mice. A single administration of the AAV9-hFXN at 6 × 1011 v.p. more than doubled the life of these mice. In fact the MCK-cre mice treated with the AAV9-hFXN were sacrificed for further molecular investigations at the age of 29 weeks without apparent symptoms. Echography analysis of the heart function clearly indicated that the cardiac systolic function was better preserved in the mice that received 6 × 1011 v.p. of AAV9-hFXN. The human frataxin protein was detected by ELISA in the heart, brain, muscles, kidney, and liver with the higher dose of virus in both mouse models. Thus, gene therapy with an AAV9-hFXN is a potential treatment of FRDA.

  12. Analysis of Yellow Striped Mutants of Zea mays Reveals Novel Loci Contributing to Iron Deficiency Chlorosis

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    David Chan-Rodriguez

    2018-02-01

    Full Text Available The micronutrient iron (Fe is essential for photosynthesis, respiration, and many other processes, but it is only sparingly soluble in aqueous solution, making adequate acquisition by plants a serious challenge. Fe is a limiting factor for plant growth on approximately 30% of the world’s arable lands. Moreover, Fe deficiency in humans is a global health issue, affecting 1.62 billion people, or about 25% of the world’s population. It is imperative that we gain a better understanding of the mechanisms that plants use to regulate iron homeostasis, since these will be important targets for future biofortification and crop improvement strategies. Grasses and non-grasses have evolved independent mechanisms for primary iron uptake from the soil. The grasses, which include most of the world’s staple grains, have evolved a distinct ‘chelation’ mechanism to acquire iron from the soil. Strong iron chelators called phytosiderophores (PSs are synthesized by grasses and secreted into the rhizosphere where they bind and solubilize Fe(III. The Fe(III-PS complex is then taken up into root cells via transporters specific for the Fe(III-PS complex. In this study, 31 novel, uncharacterized striped maize mutants available through the Maize Genetics Cooperation Stock Center (MGCSC were analyzed to determine whether their mutant phenotypes are caused by decreased iron. Many of these proved to be either pale yellow or white striped mutants. Complementation tests were performed by crossing the MGCSC mutants to ys1 and ys3 reference mutants. This allowed assignment of 10 ys1 alleles and 4 ys3 alleles among the novel mutants. In addition, four ys∗ mutant lines were identified that are not allelic to either ys1 or ys3. Three of these were characterized as being non-allelic to each other and as having low iron in leaves. These represent new genes involved in iron acquisition by maize, and future cloning of these genes may reveal novel aspects of the grass iron

  13. Interactions of iron-bound frataxin with ISCU and ferredoxin on the cysteine desulfurase complex leading to Fe-S cluster assembly.

    Science.gov (United States)

    Cai, Kai; Frederick, Ronnie O; Tonelli, Marco; Markley, John L

    2018-06-01

    Frataxin (FXN) is involved in mitochondrial iron‑sulfur (Fe-S) cluster biogenesis and serves to accelerate Fe-S cluster formation. FXN deficiency is associated with Friedreich ataxia, a neurodegenerative disease. We have used a combination of isothermal titration calorimetry and multinuclear NMR spectroscopy to investigate interactions among the components of the biological machine that carries out the assembly of iron‑sulfur clusters in human mitochondria. Our results show that FXN tightly binds a single Fe 2+ but not Fe 3+ . While FXN (with or without bound Fe 2+ ) does not bind the scaffold protein ISCU directly, the two proteins interact mutually when each is bound to the cysteine desulfurase complex ([NFS1] 2 :[ISD11] 2 :[Acp] 2 ), abbreviated as (NIA) 2 , where "N" represents the cysteine desulfurase (NFS1), "I" represents the accessory protein (ISD11), and "A" represents acyl carrier protein (Acp). FXN binds (NIA) 2 weakly in the absence of ISCU but more strongly in its presence. Fe 2+ -FXN binds to the (NIA) 2 -ISCU 2 complex without release of iron. However, upon the addition of both l-cysteine and a reductant (either reduced FDX2 or DTT), Fe 2+ is released from FXN as consistent with Fe 2+ -FXN being the proximal source of iron for Fe-S cluster assembly. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  14. Human genetic deficiencies reveal the roles of complement in the inflammatory network: lessons from nature

    DEFF Research Database (Denmark)

    Lappegård, Knut Tore; Christiansen, Dorte; Pharo, Anne

    2009-01-01

    on CD14 and inversely regulated by complement, that is, complement deficiency and complement inhibition enhanced their release. Granulocyte responses were mainly complement-dependent, whereas monocyte responses were more dependent on CD14. Notably, all responses were abolished by combined neutralization...

  15. Proteomic and comparative genomic analysis reveals adaptability of Brassica napus to phosphorus-deficient stress.

    Science.gov (United States)

    Chen, Shuisen; Ding, Guangda; Wang, Zhenhua; Cai, Hongmei; Xu, Fangsen

    2015-03-18

    Given low solubility and immobility in many soils of the world, phosphorus (P) may be the most widely studied macronutrient for plants. In an attempt to gain an insight into the adaptability of Brassica napus to P deficiency, proteome alterations of roots and leaves in two B. napus contrasting genotypes, P-efficient 'Eyou Changjia' and P-inefficient 'B104-2', under long-term low P stress and short-term P-free starvation conditions were investigated, and proteomic combined with comparative genomic analyses were conducted to interpret the interrelation of differential abundance protein species (DAPs) responding to P deficiency with quantitative trait loci (QTLs) for P deficiency tolerance. P-efficient 'Eyou Changjia' had higher dry weight and P content, and showed high tolerance to low P stress compared with P-inefficient 'B104-2'. A total of 146 DAPs were successfully identified by MALDI TOF/TOF MS, which were categorized into several groups including defense and stress response, carbohydrate and energy metabolism, signaling and regulation, amino acid and fatty acid metabolism, protein process, biogenesis and cellular component, and function unknown. 94 of 146 DAPs were mapped to a linkage map constructed by a B. napus population derived from a cross between the two genotypes, and 72 DAPs were located in the confidence intervals of QTLs for P efficiency related traits. We conclude that the identification of these DAPs and the co-location of DAPs with QTLs in the B. napus linkage genetic map provide us novel information in understanding the adaptability of B. napus to P deficiency, and helpful to isolate P-efficient genes in B. napus. Low P seriously limits the production and quality of B. napus. Proteomics and genetic linkage map were widely used to study the adaptive strategies of B. napus response to P deficiency, proteomic combined with comparative genetic analysis to investigate the correlations between DAPs and QTLs are scarce. Thus, we herein investigated

  16. The Structure of the Complex between Yeast Frataxin and Ferrochelatase: CHARACTERIZATION AND PRE-STEADY STATE REACTION OF FERROUS IRON DELIVERY AND HEME SYNTHESIS.

    Science.gov (United States)

    Söderberg, Christopher; Gillam, Mallory E; Ahlgren, Eva-Christina; Hunter, Gregory A; Gakh, Oleksandr; Isaya, Grazia; Ferreira, Gloria C; Al-Karadaghi, Salam

    2016-05-27

    Frataxin is a mitochondrial iron-binding protein involved in iron storage, detoxification, and delivery for iron sulfur-cluster assembly and heme biosynthesis. The ability of frataxin from different organisms to populate multiple oligomeric states in the presence of metal ions, e.g. Fe(2+) and Co(2+), led to the suggestion that different oligomers contribute to the functions of frataxin. Here we report on the complex between yeast frataxin and ferrochelatase, the terminal enzyme of heme biosynthesis. Protein-protein docking and cross-linking in combination with mass spectroscopic analysis and single-particle reconstruction from negatively stained electron microscopic images were used to verify the Yfh1-ferrochelatase interactions. The model of the complex indicates that at the 2:1 Fe(2+)-to-protein ratio, when Yfh1 populates a trimeric state, there are two interaction interfaces between frataxin and the ferrochelatase dimer. Each interaction site involves one ferrochelatase monomer and one frataxin trimer, with conserved polar and charged amino acids of the two proteins positioned at hydrogen-bonding distances from each other. One of the subunits of the Yfh1 trimer interacts extensively with one subunit of the ferrochelatase dimer, contributing to the stability of the complex, whereas another trimer subunit is positioned for Fe(2+) delivery. Single-turnover stopped-flow kinetics experiments demonstrate that increased rates of heme production result from monomers, dimers, and trimers, indicating that these forms are most efficient in delivering Fe(2+) to ferrochelatase and sustaining porphyrin metalation. Furthermore, they support the proposal that frataxin-mediated delivery of this potentially toxic substrate overcomes formation of reactive oxygen species. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. Internal jugular vein thrombosis associated with venous hypoplasia and protein S deficiency revealed by ultrasonography.

    Science.gov (United States)

    Lim, Byung Gun; Kim, Young Min; Kim, Heezoo; Lim, Sang Ho; Lee, Mi Kyoung

    2011-12-01

    A 41-year-old woman, who had no thrombotic risk factors and past history except congenital scoliosis, underwent central venous catheterization (CVC) before correction of the scoliosis. When internal jugular vein (IJV) catheterization using the anatomical landmark technique failed, CVC under ultrasound guidance was tried. As a consequence, thrombosis and hypoplasia of the right IJV were incidentally detected by ultrasonography. Central venous catheters were then successfully placed in other veins under ultrasound guidance. Also, after examinations to rule out the possibility of pulmonary embolism and to clarify the causes of the IJV thrombosis, the patient was found to have protein S deficiency. CVC under ultrasound guidance should be recommended to prevent the failure of cannulation and complications such as thromboembolism in patients who could possibly have anomalies of vessels as a result of anatomical deformities caused by severe scoliosis, even if patients do not have thrombotic risk factors such as a history of central catheter insertion or intravenous drug abuse, cancer, advanced age, cerebral infarction, and left ventricular dysfunction. Also, if venous thrombosis is found in patients without predisposing risk factors, one should ascertain the cause of the hypercoagulable state, for example protein S deficiency, and perform appropriate treatment and prevention of venous thromboembolism.

  18. Phonological abilities in literacy-impaired children: Brain potentials reveal deficient phoneme discrimination, but intact prosodic processing

    Directory of Open Access Journals (Sweden)

    Claudia Männel

    2017-02-01

    Full Text Available Intact phonological processing is crucial for successful literacy acquisition. While individuals with difficulties in reading and spelling (i.e., developmental dyslexia are known to experience deficient phoneme discrimination (i.e., segmental phonology, findings concerning their prosodic processing (i.e., suprasegmental phonology are controversial. Because there are no behavior-independent studies on the underlying neural correlates of prosodic processing in dyslexia, these controversial findings might be explained by different task demands. To provide an objective behavior-independent picture of segmental and suprasegmental phonological processing in impaired literacy acquisition, we investigated event-related brain potentials during passive listening in typically and poor-spelling German school children. For segmental phonology, we analyzed the Mismatch Negativity (MMN during vowel length discrimination, capturing automatic auditory deviancy detection in repetitive contexts. For suprasegmental phonology, we analyzed the Closure Positive Shift (CPS that automatically occurs in response to prosodic boundaries. Our results revealed spelling group differences for the MMN, but not for the CPS, indicating deficient segmental, but intact suprasegmental phonological processing in poor spellers. The present findings point towards a differential role of segmental and suprasegmental phonology in literacy disorders and call for interventions that invigorate impaired literacy by utilizing intact prosody in addition to training deficient phonemic awareness.

  19. Temporal gene expression profiling reveals CEBPD as a candidate regulator of brain disease in prosaposin deficient mice

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    Ran Huimin

    2008-08-01

    Full Text Available Abstract Background Prosaposin encodes, in tandem, four small acidic activator proteins (saposins with specificities for glycosphingolipid (GSL hydrolases in lysosomes. Extensive GSL storage occurs in various central nervous system regions in mammalian prosaposin deficiencies. Results Our hypomorphic prosaposin deficient mouse, PS-NA, exhibited 45% WT levels of brain saposins and showed neuropathology that included neuronal GSL storage and Purkinje cell loss. Impairment of neuronal function was observed as early as 6 wks as demonstrated by the narrow bridges tests. Temporal transcriptome microarray analyses of brain tissues were conducted with mRNA from three prosaposin deficient mouse models: PS-NA, prosaposin null (PS-/- and a V394L/V394L glucocerebrosidase mutation combined with PS-NA (4L/PS-NA. Gene expression alterations in cerebrum and cerebellum were detectable at birth preceding the neuronal deficits. Differentially expressed genes encompassed a broad spectrum of cellular functions. The number of down-regulated genes was constant, but up-regulated gene numbers increased with age. CCAAT/enhancer-binding protein delta (CEBPD was the only up-regulated transcription factor in these two brain regions of all three models. Network analyses revealed that CEBPD has functional relationships with genes in transcription, pro-inflammation, cell death, binding, myelin and transport. Conclusion These results show that: 1 Regionally specific gene expression abnormalities precede the brain histological and neuronal function changes, 2 Temporal gene expression profiles provide insights into the molecular mechanism during the GSL storage disease course, and 3 CEBPD is a candidate regulator of brain disease in prosaposin deficiency to participate in modulating disease acceleration or progression.

  20. Brain transcriptional responses to high-fat diet in Acads-deficient mice reveal energy sensing pathways.

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    Claudia Kruger

    Full Text Available How signals from fatty acid metabolism are translated into changes in food intake remains unclear. Previously we reported that mice with a genetic inactivation of Acads (acyl-coenzyme A dehydrogenase, short-chain, the enzyme responsible for mitochondrial beta-oxidation of C4-C6 short-chain fatty acids (SCFAs, shift consumption away from fat and toward carbohydrate when offered a choice between diets. In the current study, we sought to indentify candidate genes and pathways underlying the effects of SCFA oxidation deficiency on food intake in Acads-/- mice.We performed a transcriptional analysis of gene expression in brain tissue of Acads-/- and Acads+/+ mice fed either a high-fat (HF or low-fat (LF diet for 2 d. Ingenuity Pathway Analysis revealed three top-scoring pathways significantly modified by genotype or diet: oxidative phosphorylation, mitochondrial dysfunction, and CREB signaling in neurons. A comparison of statistically significant responses in HF Acads-/- vs. HF Acads+/+ (3917 and Acads+/+ HF vs. LF Acads+/+ (3879 revealed 2551 genes or approximately 65% in common between the two experimental comparisons. All but one of these genes were expressed in opposite direction with similar magnitude, demonstrating that HF-fed Acads-deficient mice display transcriptional responses that strongly resemble those of Acads+/+ mice fed LF diet. Intriguingly, genes involved in both AMP-kinase regulation and the neural control of food intake followed this pattern. Quantitative RT-PCR in hypothalamus confirmed the dysregulation of genes in these pathways. Western blotting showed an increase in hypothalamic AMP-kinase in Acads-/- mice and HF diet increased, a key protein in an energy-sensing cascade that responds to depletion of ATP.Our results suggest that the decreased beta-oxidation of short-chain fatty acids in Acads-deficient mice fed HF diet produces a state of energy deficiency in the brain and that AMP-kinase may be the cellular energy

  1. Ex vivo stretch reveals altered mechanical properties of isolated dystrophin-deficient hearts.

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    Matthew S Barnabei

    Full Text Available Duchenne muscular dystrophy (DMD is a progressive and fatal disease of muscle wasting caused by loss of the cytoskeletal protein dystrophin. In the heart, DMD results in progressive cardiomyopathy and dilation of the left ventricle through mechanisms that are not fully understood. Previous reports have shown that loss of dystrophin causes sarcolemmal instability and reduced mechanical compliance of isolated cardiac myocytes. To expand upon these findings, here we have subjected the left ventricles of dystrophin-deficient mdx hearts to mechanical stretch. Unexpectedly, isolated mdx hearts showed increased left ventricular (LV compliance compared to controls during stretch as LV volume was increased above normal end diastolic volume. During LV chamber distention, sarcomere lengths increased similarly in mdx and WT hearts despite greater excursions in volume of mdx hearts. This suggests that the mechanical properties of the intact heart cannot be modeled as a simple extrapolation of findings in single cardiac myocytes. To explain these findings, a model is proposed in which disruption of the dystrophin-glycoprotein complex perturbs cell-extracellular matrix contacts and promotes the apparent slippage of myocytes past each other during LV distension. In comparison, similar increases in LV compliance were obtained in isolated hearts from β-sarcoglycan-null and laminin-α(2 mutant mice, but not in dysferlin-null mice, suggesting that increased whole-organ compliance in mdx mice is a specific effect of disrupted cell-extracellular matrix contacts and not a general consequence of cardiomyopathy via membrane defect processes. Collectively, these findings suggest a novel and cell-death independent mechanism for the progressive pathological LV dilation that occurs in DMD.

  2. Expression analysis revealing destabilizing mutations in phosphomannomutase 2 deficiency (PMM2-CDG): expression analysis of PMM2-CDG mutations.

    Science.gov (United States)

    Vega, Ana Isabel; Pérez-Cerdá, Celia; Abia, David; Gámez, Alejandra; Briones, Paz; Artuch, Rafael; Desviat, Lourdes R; Ugarte, Magdalena; Pérez, Belén

    2011-08-01

    Deficiency of phosphomannomutase (PMM2, MIM#601785) is the most common congenital disorder of glycosylation. Herein we report the genetic analysis of 22 Spanish PMM2 deficient patients and the functional analysis of 14 nucleotide changes in a prokaryotic expression system in order to elucidate their molecular pathogenesis. PMM2 activity assay revealed the presence of six protein changes with no enzymatic activities (p.R123Q, p.R141H, p.F157S, p.P184T, p.F207S and p.D209G) and seven mild protein changes with residual activities ranging from 16 to 54% (p.L32R, p.V44A p.D65Y, p.P113L p.T118S, p.T237M and p.C241S) and also one variant change with normal activity (p.E197A). The results obtained from Western blot analysis, degradation time courses of 11 protein changes and structural analysis of the PMM2 protein, suggest that the loss-of-function of most mutant proteins is based on their increased susceptibility to degradation or aggregation compared to the wild type protein, considering PMM2 deficiency as a conformational disease. We have identified exclusively catalytic protein change (p.D209G), catalytic protein changes affecting protein stability (p.R123Q and p.R141H), two protein changes disrupting the dimer interface (p.P113L and p.T118S) and several misfolding changes (p.L32R, p.V44A, p.D65Y, p.F157S, p.P184T, p.F207S, p.T237M and p.C241S). Our current work opens a promising therapeutic option using pharmacological chaperones to revert the effect of the characterized misfolding mutations identified in a wide range of PMM2 deficient patients.

  3. Overexpression of the yeast frataxin homolog (Yfh1): contrasting effects on iron-sulfur cluster assembly, heme synthesis and resistance to oxidative stress

    DEFF Research Database (Denmark)

    Seguin, Alexandra; Bayot, Aurélien; Dancis, Andrew

    2009-01-01

    of 2muYFH1 cells compared to wild-type cells. To our knowledge, this work is the first description where major frataxin-related phenotypes ([Fe-S] cluster assembly and heme synthesis) can be split in vivo, suggesting that frataxin has independent roles in both processes, and that the optimal conditions......Friedreich's ataxia is generally associated with defects in [Fe-S] cluster assembly/stability and heme synthesis and strong susceptibility to oxidative stress. We used the yeast (Saccharomyces cerevisiae) model of Friedreich's ataxia to study the physiological consequences of modulating...... for these independent roles are different....

  4. Deficiency in the mitochondrial apoptotic pathway reveals the toxic potential of autophagy under ER stress conditions.

    Science.gov (United States)

    Deegan, Shane; Saveljeva, Svetlana; Logue, Susan E; Pakos-Zebrucka, Karolina; Gupta, Sanjeev; Vandenabeele, Peter; Bertrand, Mathieu J M; Samali, Afshin

    2014-01-01

    Endoplasmic reticulum (ER) stress-induced cell death is normally associated with activation of the mitochondrial apoptotic pathway, which is characterized by CYCS (cytochrome c, somatic) release, apoptosome formation, and caspase activation, resulting in cell death. In this study, we demonstrate that under conditions of ER stress cells devoid of CASP9/caspase-9 or BAX and BAK1, and therefore defective in the mitochondrial apoptotic pathway, still undergo a delayed form of cell death associated with the activation of caspases, therefore revealing the existence of an alternative stress-induced caspase activation pathway. We identified CASP8/caspase-8 as the apical protease in this caspase cascade, and found that knockdown of either of the key autophagic genes, ATG5 or ATG7, impacted on CASP8 activation and cell death induction, highlighting the crucial role of autophagy in the activation of this novel ER stress-induced death pathway. In line with this, we identified a protein complex composed of ATG5, FADD, and pro-CASP8 whose assembly coincides with caspase activation and cell death induction. Together, our results reveal the toxic potential of autophagy in cells undergoing ER stress that are defective in the mitochondrial apoptotic pathway, and suggest a model in which the autophagosome functions as a platform facilitating pro-CASP8 activation. Chemoresistance, a common problem in the treatment of cancer, is frequently caused by the downregulation of key mitochondrial death effector proteins. Alternate stress-induced apoptotic pathways, such as the one described here, may become of particular relevance for tackling the problem of chemoresistance in cancer cells.

  5. A Shotgun Proteomic Approach Reveals That Fe Deficiency Causes Marked Changes in the Protein Profiles of Plasma Membrane and Detergent-Resistant Microdomain Preparations from Beta vulgaris Roots.

    Science.gov (United States)

    Gutierrez-Carbonell, Elain; Takahashi, Daisuke; Lüthje, Sabine; González-Reyes, José Antonio; Mongrand, Sébastien; Contreras-Moreira, Bruno; Abadía, Anunciación; Uemura, Matsuo; Abadía, Javier; López-Millán, Ana Flor

    2016-08-05

    In the present study we have used label-free shotgun proteomic analysis to examine the effects of Fe deficiency on the protein profiles of highly pure sugar beet root plasma membrane (PM) preparations and detergent-resistant membranes (DRMs), the latter as an approach to study microdomains. Altogether, 545 proteins were detected, with 52 and 68 of them changing significantly with Fe deficiency in PM and DRM, respectively. Functional categorization of these proteins showed that signaling and general and vesicle-related transport accounted for approximately 50% of the differences in both PM and DRM, indicating that from a qualitative point of view changes induced by Fe deficiency are similar in both preparations. Results indicate that Fe deficiency has an impact in phosphorylation processes at the PM level and highlight the involvement of signaling proteins, especially those from the 14-3-3 family. Lipid profiling revealed Fe-deficiency-induced decreases in phosphatidic acid derivatives, which may impair vesicle formation, in agreement with the decreases measured in proteins related to intracellular trafficking and secretion. The modifications induced by Fe deficiency in the relative enrichment of proteins in DRMs revealed the existence of a group of cytoplasmic proteins that appears to be more attached to the PM in conditions of Fe deficiency.

  6. IL-15 deficient tax mice reveal a role for IL-1α in tumor immunity.

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    Daniel A Rauch

    Full Text Available IL-15 is recognized as a promising candidate for tumor immunotherapy and has been described as both a promoter of cancer and a promoter of anti-cancer immunity. IL-15 was discovered in cells transformed by HTLV-1, the etiologic agent of adult T cell leukemia/lymphoma (ATL and the human retrovirus that carries the Tax oncogene. We have developed the TAX-LUC mouse model of ATL in which Tax expression drives both malignant transformation and luciferase expression, enabling non-invasive imaging of tumorigenesis in real time. To identify the role of IL-15 in spontaneous development of lymphoma in vivo, an IL-15(-/- TAX-LUC strain was developed and examined. The absence of IL-15 resulted in aggressive tumor growth and accelerated mortality and demonstrated that IL-15 was not required for Tax-mediated lymphoma but was essential for anti-tumor immunity. Further analysis revealed a unique transcriptional profile in tumor cells that arise in the absence of IL-15 that included a significant increase in the expression of IL-1α and IL-1α-regulated cytokines. Moreover, anti-IL-1α antibodies and an IL-1 receptor antagonist (Anakinra were used to interrogate the potential of IL-1α targeted therapies in this model. Taken together, these findings identify IL-15 and IL-1α as therapeutic targets in lymphoma.

  7. Long-term boron-deficiency-responsive genes revealed by cDNA-AFLP differ between Citrus sinensis roots and leaves

    Science.gov (United States)

    Lu, Yi-Bin; Qi, Yi-Ping; Yang, Lin-Tong; Lee, Jinwook; Guo, Peng; Ye, Xin; Jia, Meng-Yang; Li, Mei-Li; Chen, Li-Song

    2015-01-01

    Seedlings of Citrus sinensis (L.) Osbeck were supplied with boron (B)-deficient (without H3BO3) or -sufficient (10 μM H3BO3) nutrient solution for 15 weeks. We identified 54 (38) and 38 (45) up (down)-regulated cDNA-AFLP bands (transcript-derived fragments, TDFs) from B-deficient leaves and roots, respectively. These TDFs were mainly involved in protein and amino acid metabolism, carbohydrate and energy metabolism, nucleic acid metabolism, cell transport, signal transduction, and stress response and defense. The majority of the differentially expressed TDFs were isolated only from B-deficient roots or leaves, only seven TDFs with the same GenBank ID were isolated from the both. In addition, ATP biosynthesis-related TDFs were induced in B-deficient roots, but unaffected in B-deficient leaves. Most of the differentially expressed TDFs associated with signal transduction and stress defense were down-regulated in roots, but up-regulated in leaves. TDFs related to protein ubiquitination and proteolysis were induced in B-deficient leaves except for one TDF, while only two down-regulated TDFs associated with ubiquitination were detected in B-deficient roots. Thus, many differences existed in long-term B-deficiency-responsive genes between roots and leaves. In conclusion, our findings provided a global picture of the differential responses occurring in B-deficient roots and leaves and revealed new insight into the different adaptive mechanisms of C. sinensis roots and leaves to B-deficiency at the transcriptional level. PMID:26284101

  8. Iron-induced oligomerization of human FXN81-210 and bacterial CyaY frataxin and the effect of iron chelators

    DEFF Research Database (Denmark)

    Ahlgren, Eva Christina; Fekry, Mostafa; Wiemann, Mathias

    2017-01-01

    long forms, FXN42-210 and FXN56-210, have been shown to spontaneously form oligomeric particles stabilized by the extended N-terminal sequence. The short variant FXN81-210, on other hand, has only been observed in the monomeric state. However, a highly homologous E. coli frataxin CyaY, which also lacks...

  9. Liver Growth Factor (LGF Upregulates Frataxin Protein Expression and Reduces Oxidative Stress in Friedreich’s Ataxia Transgenic Mice

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    Lucía Calatrava-Ferreras

    2016-12-01

    Full Text Available Friedreich’s ataxia (FA is a severe disorder with autosomal recessive inheritance that is caused by the abnormal expansion of GAA repeat in intron 1 of FRDA gen. This alteration leads to a partial silencing of frataxin transcription, causing a multisystem disorder disease that includes neurological and non-neurological damage. Recent studies have proven the effectiveness of neurotrophic factors in a number of neurodegenerative diseases. Therefore, we intend to determine if liver growth factor (LGF, which has a demonstrated antioxidant and neuroprotective capability, could be a useful therapy for FA. To investigate the potential therapeutic activity of LGF we used transgenic mice of the FXNtm1MknTg (FXNYG8Pook strain. In these mice, intraperitoneal administration of LGF (1.6 μg/mouse exerted a neuroprotective effect on neurons of the lumbar spinal cord and improved cardiac hypertrophy. Both events could be the consequence of the increment in frataxin expression induced by LGF in spinal cord (1.34-fold and heart (1.2-fold. LGF also upregulated by 2.6-fold mitochondrial chain complex IV expression in spinal cord, while in skeletal muscle it reduced the relation oxidized glutathione/reduced glutathione. Since LGF partially restores motor coordination, we propose LGF as a novel factor that may be useful in the treatment of FA.

  10. Iron homeostasis in Arabidopsis thaliana: transcriptomic analyses reveal novel FIT-regulated genes, iron deficiency marker genes and functional gene networks.

    Science.gov (United States)

    Mai, Hans-Jörg; Pateyron, Stéphanie; Bauer, Petra

    2016-10-03

    FIT (FER-LIKE IRON DEFICIENCY-INDUCED TRANSCRIPTION FACTOR) is the central regulator of iron uptake in Arabidopsis thaliana roots. We performed transcriptome analyses of six day-old seedlings and roots of six week-old plants using wild type, a fit knock-out mutant and a FIT over-expression line grown under iron-sufficient or iron-deficient conditions. We compared genes regulated in a FIT-dependent manner depending on the developmental stage of the plants. We assembled a high likelihood dataset which we used to perform co-expression and functional analysis of the most stably iron deficiency-induced genes. 448 genes were found FIT-regulated. Out of these, 34 genes were robustly FIT-regulated in root and seedling samples and included 13 novel FIT-dependent genes. Three hundred thirty-one genes showed differential regulation in response to the presence and absence of FIT only in the root samples, while this was the case for 83 genes in the seedling samples. We assembled a virtual dataset of iron-regulated genes based on a total of 14 transcriptomic analyses of iron-deficient and iron-sufficient wild-type plants to pinpoint the best marker genes for iron deficiency and analyzed this dataset in depth. Co-expression analysis of this dataset revealed 13 distinct regulons part of which predominantly contained functionally related genes. We could enlarge the list of FIT-dependent genes and discriminate between genes that are robustly FIT-regulated in roots and seedlings or only in one of those. FIT-regulated genes were mostly induced, few of them were repressed by FIT. With the analysis of a virtual dataset we could filter out and pinpoint new candidates among the most reliable marker genes for iron deficiency. Moreover, co-expression and functional analysis of this virtual dataset revealed iron deficiency-induced and functionally distinct regulons.

  11. Transcriptome analyses of a salt-tolerant cytokinin-deficient mutant reveal differential regulation of salt stress response by cytokinin deficiency.

    Directory of Open Access Journals (Sweden)

    Rie Nishiyama

    Full Text Available Soil destruction by abiotic environmental conditions, such as high salinity, has resulted in dramatic losses of arable land, giving rise to the need of studying mechanisms of plant adaptation to salt stress aimed at creating salt-tolerant plants. Recently, it has been reported that cytokinins (CKs regulate plant environmental stress responses through two-component systems. A decrease in endogenous CK levels could enhance salt and drought stress tolerance. Here, we have investigated the global transcriptional change caused by a reduction in endogenous CK content under both normal and salt stress conditions. Ten-day-old Arabidopsis thaliana wild-type (WT and CK-deficient ipt1,3,5,7 plants were transferred to agar plates containing either 0 mM (control or 200 mM NaCl and maintained at normal growth conditions for 24 h. Our experimental design allowed us to compare transcriptome changes under four conditions: WT-200 mM vs. WT-0 mM, ipt1,3,5,7-0 mM vs. WT-0 mM, ipt1,3,5,7-200 mM vs. ipt1,3,5,7-0 mM and ipt1,3,5,7-200 mM vs. WT-200 mM NaCl. Our results indicated that the expression of more than 10% of all of the annotated Arabidopsis genes was altered by CK deficiency under either normal or salt stress conditions when compared to WT. We found that upregulated expression of many genes encoding either regulatory proteins, such as NAC, DREB and ZFHD transcription factors and the calcium sensor SOS3, or functional proteins, such as late embryogenesis-abundant proteins, xyloglucan endo-transglycosylases, glycosyltransferases, glycoside hydrolases, defensins and glyoxalase I family proteins, may contribute to improved salt tolerance of CK-deficient plants. We also demonstrated that the downregulation of photosynthesis-related genes and the upregulation of several NAC genes may cause the altered morphological phenotype of CK-deficient plants. This study highlights the impact of CK regulation on the well-known stress-responsive signaling pathways, which

  12. Switch junction sequences in PMS2-deficient mice reveal a microhomology-mediated mechanism of Ig class switch recombination

    Science.gov (United States)

    Ehrenstein, Michael R.; Rada, Cristina; Jones, Anne-Marie; Milstein, César; Neuberger, Michael S.

    2001-01-01

    Isotype switching involves a region-specific, nonhomologous recombinational deletion that has been suggested to occur by nonhomologous joining of broken DNA ends. Here, we find increased donor/acceptor homology at switch junctions from PMS2-deficient mice and propose that class switching can occur by microhomology-mediated end-joining. Interestingly, although isotype switching and somatic hypermutation show many parallels, we confirm that PMS2 deficiency has no major effect on the pattern of nucleotide substitutions generated during somatic hypermutation. This finding is in contrast to MSH2 deficiency. With MSH2, the altered pattern of switch recombination and hypermutation suggests parallels in the mechanics of the two processes, whereas the fact that PMS2 deficiency affects only switch recombination may reflect differences in the pathways of break resolution. PMID:11717399

  13. Sensory Neuronopathy Revealing Severe Vitamin B12 Deficiency in a Patient with Anorexia Nervosa: An Often-Forgotten Reversible Cause

    Directory of Open Access Journals (Sweden)

    Jérôme Franques

    2017-03-01

    Full Text Available Vitamin B12 (B12 deficiency is known to be associated with various neurological manifestations. Although central manifestations such as dementia or subacute combined degeneration are the most classic, neurological manifestations also include sensory neuropathies. However, B12 deficiency is still rarely integrated as a potential cause of sensory neuronopathy. Moreover, as many medical conditions can falsely normalize serum B12 levels even in the context of a real B12 deficiency, some cases may easily remain underdiagnosed. We report the illustrating case of an anorexic patient with sensory neuronopathy and consistently normal serum B12 levels. After all classical causes of sensory neuronopathy were ruled out, her clinical and electrophysiological conditions first worsened after folate administration, but finally improved dramatically after B12 administration. B12 deficiency should be systematically part of the etiologic workup of sensory neuronopathy, especially in a high risk context such as anorexia nervosa.

  14. Gene expression deregulation in postnatal skeletal muscle of TK2 deficient mice reveals a lower pool of proliferating myogenic progenitor cells.

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    João A Paredes

    Full Text Available Loss of thymidine kinase 2 (TK2 causes a heterogeneous myopathic form of mitochondrial DNA (mtDNA depletion syndrome (MDS in humans that predominantly affects skeletal muscle tissue. In mice, TK2 deficiency also affects several tissues in addition to skeletal muscle, including brain, heart, adipose tissue, kidneys and causes death about 3 weeks after birth. We analysed skeletal muscle and heart muscle tissues of Tk2 knockout mice at postnatal development phase and observed that TK2 deficient pups grew slower and their skeletal muscles appeared significantly underdeveloped, whereas heart was close to normal in size. Both tissues showed mtDNA depletion and mitochondria with altered ultrastructure, as revealed by transmission electron microscopy. Gene expression microarray analysis showed a strong down-regulation of genes involved in cell cycle and cell proliferation in both tissues, suggesting a lower pool of undifferentiated proliferating cells. Analysis of isolated primary myoblasts from Tk2 knockout mice showed slow proliferation, less ability to differentiate and signs of premature senescence, even in absence of mtDNA depletion. Our data demonstrate that TK2 deficiency disturbs myogenic progenitor cells function in postnatal skeletal muscle and we propose this as one of the causes of underdeveloped phenotype and myopathic characteristic of the TK2 deficient mice, in addition to the progressive mtDNA depletion, mitochondrial damage and respiratory chain deficiency in post-mitotic differentiated tissue.

  15. Gene expression deregulation in postnatal skeletal muscle of TK2 deficient mice reveals a lower pool of proliferating myogenic progenitor cells.

    Science.gov (United States)

    Paredes, João A; Zhou, Xiaoshan; Höglund, Stefan; Karlsson, Anna

    2013-01-01

    Loss of thymidine kinase 2 (TK2) causes a heterogeneous myopathic form of mitochondrial DNA (mtDNA) depletion syndrome (MDS) in humans that predominantly affects skeletal muscle tissue. In mice, TK2 deficiency also affects several tissues in addition to skeletal muscle, including brain, heart, adipose tissue, kidneys and causes death about 3 weeks after birth. We analysed skeletal muscle and heart muscle tissues of Tk2 knockout mice at postnatal development phase and observed that TK2 deficient pups grew slower and their skeletal muscles appeared significantly underdeveloped, whereas heart was close to normal in size. Both tissues showed mtDNA depletion and mitochondria with altered ultrastructure, as revealed by transmission electron microscopy. Gene expression microarray analysis showed a strong down-regulation of genes involved in cell cycle and cell proliferation in both tissues, suggesting a lower pool of undifferentiated proliferating cells. Analysis of isolated primary myoblasts from Tk2 knockout mice showed slow proliferation, less ability to differentiate and signs of premature senescence, even in absence of mtDNA depletion. Our data demonstrate that TK2 deficiency disturbs myogenic progenitor cells function in postnatal skeletal muscle and we propose this as one of the causes of underdeveloped phenotype and myopathic characteristic of the TK2 deficient mice, in addition to the progressive mtDNA depletion, mitochondrial damage and respiratory chain deficiency in post-mitotic differentiated tissue.

  16. An RNA-Seq transcriptome analysis of orthophosphate-deficient white lupin reveals novel insights into phosphorus acclimation in plants.

    Science.gov (United States)

    O'Rourke, Jamie A; Yang, S Samuel; Miller, Susan S; Bucciarelli, Bruna; Liu, Junqi; Rydeen, Ariel; Bozsoki, Zoltan; Uhde-Stone, Claudia; Tu, Zheng Jin; Allan, Deborah; Gronwald, John W; Vance, Carroll P

    2013-02-01

    Phosphorus, in its orthophosphate form (P(i)), is one of the most limiting macronutrients in soils for plant growth and development. However, the whole-genome molecular mechanisms contributing to plant acclimation to P(i) deficiency remain largely unknown. White lupin (Lupinus albus) has evolved unique adaptations for growth in P(i)-deficient soils, including the development of cluster roots to increase root surface area. In this study, we utilized RNA-Seq technology to assess global gene expression in white lupin cluster roots, normal roots, and leaves in response to P(i) supply. We de novo assembled 277,224,180 Illumina reads from 12 complementary DNA libraries to build what is to our knowledge the first white lupin gene index (LAGI 1.0). This index contains 125,821 unique sequences with an average length of 1,155 bp. Of these sequences, 50,734 were transcriptionally active (reads per kilobase per million reads ≥ 3), representing approximately 7.8% of the white lupin genome, using the predicted genome size of Lupinus angustifolius as a reference. We identified a total of 2,128 sequences differentially expressed in response to P(i) deficiency with a 2-fold or greater change and P ≤ 0.05. Twelve sequences were consistently differentially expressed due to P(i) deficiency stress in three species, Arabidopsis (Arabidopsis thaliana), potato (Solanum tuberosum), and white lupin, making them ideal candidates to monitor the P(i) status of plants. Additionally, classic physiological experiments were coupled with RNA-Seq data to examine the role of cytokinin and gibberellic acid in P(i) deficiency-induced cluster root development. This global gene expression analysis provides new insights into the biochemical and molecular mechanisms involved in the acclimation to P(i) deficiency.

  17. Liver failure with coagulopathy, hyperammonemia and cyclic vomiting in a toddler revealed to have combined heterozygosity for genes involved with ornithine transcarbamylase deficiency and Wilson disease.

    Science.gov (United States)

    Mira, Valerie; Boles, Richard G

    2012-01-01

    A girl with a 2 month history of cyclic episodes of vomiting, diarrhea, and lethargy lasting 2-3 days each presented with acute hepatopathy (ALT 3,500 IU/L) with coagulopathy (PT 55 s) and hyperammonemia (207 μmol/L) at age 1½ years. Biochemical and molecular analyzes revealed ornithine transcarbamylase (OTC) deficiency. While laboratory signs of mild hepatocellular dysfunction are common in OTC deficiency, substantial liver failure with coagulopathy is generally not seen, although four others cases have been reported, three of which presented with cyclic vomiting. Further evaluation in our case revealed elevated urine (198.8 μg/g creatinine) and liver (103 μg/g dry weight) copper content, and a heterozygous mutation in the Wilson disease gene, ATP7B. Our patient, now aged 5 years, has remained in excellent health with normal growth and development on fasting avoidance, a modified vegan diet, and sodium phenylbutyrate.These five cases demonstrate that generalized liver dysfunction/failure is a potential serious complication of OTC deficiency, although not a common one, and suggests that an ALT and PT should be obtained in OTC patients during episodes of hyperammonemia. Cyclic vomiting is a known presentation of OTC deficiency; it is not known if comorbid liver failure predisposes toward this phenotype. We propose that the heterozygote state in ATP7B increases the liver copper content, thus predisposing our patient with OTC deficiency to develop liver failure during a hyperammonemic episode. Our present case is an example of the opportunity of molecular diagnostics to identify putative modifier genes in patients with atypical presentations of genetic disorders.

  18. A mouse model for creatine transporter deficiency reveals early onset cognitive impairment and neuropathology associated with brain aging.

    Science.gov (United States)

    Baroncelli, Laura; Molinaro, Angelo; Cacciante, Francesco; Alessandrì, Maria Grazia; Napoli, Debora; Putignano, Elena; Tola, Jonida; Leuzzi, Vincenzo; Cioni, Giovanni; Pizzorusso, Tommaso

    2016-10-01

    Mutations in the creatine (Cr) transporter (CrT) gene lead to cerebral creatine deficiency syndrome-1 (CCDS1), an X-linked metabolic disorder characterized by cerebral Cr deficiency causing intellectual disability, seizures, movement and autistic-like behavioural disturbances, language and speech impairment. Since no data are available about the neural and molecular underpinnings of this disease, we performed a longitudinal analysis of behavioural and pathological alterations associated with CrT deficiency in a CCDS1 mouse model. We found precocious cognitive and autistic-like defects, mimicking the early key features of human CCDS1. Moreover, mutant mice displayed a progressive impairment of short and long-term declarative memory denoting an early brain aging. Pathological examination showed a prominent loss of GABAergic synapses, marked activation of microglia, reduction of hippocampal neurogenesis and the accumulation of autofluorescent lipofuscin. Our data suggest that brain Cr depletion causes both early intellectual disability and late progressive cognitive decline, and identify novel targets to design intervention strategies aimed at overcoming brain CCDS1 alterations. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  19. Two novel cases of cerebral haemorrhages at the neonatal period associated with inherited factor VII deficiency, one of them revealing a new nonsense mutation (Ser52Stop).

    Science.gov (United States)

    Giansily-Blaizot, Muriel; Aguilar-Martinez, Patricia; Briquel, Marie-Elisabeth; d'Oiron, Roseline; De Maistre, Emmanuel; Epelbaum, Serge; Schved, Jean-François

    2003-02-01

    Factor VII (FVII) is a plasma glycoprotein that plays a key role in the initiation of blood coagulation cascade. Inherited FVII deficiency is a rare autosomal recessive disorder with a wide heterogeneous clinical pattern. The severe form may be associated with intracranial haemorrhages occurring closely to birth with a high mortality rate. In the present article, we report two novel cases of neonatal intracerebral bleeding associated with FVII activity levels below 1% of normal. FVII genotyping investigations revealed particular genotypes including the deleterious Cys135Arg mutation and a novel Ser52Stop nonsense mutation at the homozygous state. Both mutations, through different mechanisms, are expected to be inconsistent with the production of functional FVII. These putative mechanisms are discussed through a review of the literature on phenotypic and genotypic characteristics of cerebral haemorrhages in severe inherited FVII deficiency.

  20. Short alleles revealed by PCR demonstrate no heterozygote deficiency at minisatellite loci D1S7, D7S21, and D12S11

    Energy Technology Data Exchange (ETDEWEB)

    Alonso, S.; Castro, A.; Fernandez-Fernandez, I.; Pancorbo, M.M. de [Universidad del Pais Vasco, Vizcaya (Spain)

    1997-02-01

    Short VNTR alleles that go undetected after conventional Southern blot hybridization may constitute an alternative explanation for the heterozygosity deficiency observed at some minisatellite loci. To examine this hypothesis, we have employed a screening procedure based on PCR amplification of those individuals classified as homozygotes in our databases for the loci D1S7, D7S21, and D12S11. The results obtained indicate that the frequency of these short alleles is related to the heterozygosity deficiency observed. For the most polymorphic locus, D1S7, {approximately}60% of those individuals previously classified as homozygotes were in fact heterozygotes for a short allele. After the inclusion of these new alleles, the agreement between observed and expected heterozygosity, along with other statistical tests employed, provide additional evidence for lack of population substructuring. Comparisons of allele frequency distributions reveal greater differences between racial groups than between closely related populations. 45 refs., 3 figs., 6 tabs.

  1. Intranasal siRNA administration reveals IGF2 deficiency contributes to impaired cognition in Fragile X syndrome mice.

    Science.gov (United States)

    Pardo, Marta; Cheng, Yuyan; Velmeshev, Dmitry; Magistri, Marco; Eldar-Finkelman, Hagit; Martinez, Ana; Faghihi, Mohammad A; Jope, Richard S; Beurel, Eleonore

    2017-03-23

    Molecular mechanisms underlying learning and memory remain imprecisely understood, and restorative interventions are lacking. We report that intranasal administration of siRNAs can be used to identify targets important in cognitive processes and to improve genetically impaired learning and memory. In mice modeling the intellectual deficiency of Fragile X syndrome, intranasally administered siRNA targeting glycogen synthase kinase-3β (GSK3β), histone deacetylase-1 (HDAC1), HDAC2, or HDAC3 diminished cognitive impairments. In WT mice, intranasally administered brain-derived neurotrophic factor (BDNF) siRNA or HDAC4 siRNA impaired learning and memory, which was partially due to reduced insulin-like growth factor-2 (IGF2) levels because the BDNF siRNA- or HDAC4 siRNA-induced cognitive impairments were ameliorated by intranasal IGF2 administration. In Fmr1 -/- mice, hippocampal IGF2 was deficient, and learning and memory impairments were ameliorated by IGF2 intranasal administration. Therefore intranasal siRNA administration is an effective means to identify mechanisms regulating cognition and to modulate therapeutic targets.

  2. A zebrafish model of congenital disorders of glycosylation with phosphomannose isomerase deficiency reveals an early opportunity for corrective mannose supplementation

    Directory of Open Access Journals (Sweden)

    Jaime Chu

    2013-01-01

    Individuals with congenital disorders of glycosylation (CDG have recessive mutations in genes required for protein N-glycosylation, resulting in multi-systemic disease. Despite the well-characterized biochemical consequences in these individuals, the underlying cellular defects that contribute to CDG are not well understood. Synthesis of the lipid-linked oligosaccharide (LLO, which serves as the sugar donor for the N-glycosylation of secretory proteins, requires conversion of fructose-6-phosphate to mannose-6-phosphate via the phosphomannose isomerase (MPI enzyme. Individuals who are deficient in MPI present with bleeding, diarrhea, edema, gastrointestinal bleeding and liver fibrosis. MPI-CDG patients can be treated with oral mannose supplements, which is converted to mannose-6-phosphate through a minor complementary metabolic pathway, restoring protein glycosylation and ameliorating most symptoms, although liver disease continues to progress. Because Mpi deletion in mice causes early embryonic lethality and thus is difficult to study, we used zebrafish to establish a model of MPI-CDG. We used a morpholino to block mpi mRNA translation and established a concentration that consistently yielded 13% residual Mpi enzyme activity at 4 days post-fertilization (dpf, which is within the range of MPI activity detected in fibroblasts from MPI-CDG patients. Fluorophore-assisted carbohydrate electrophoresis detected decreased LLO and N-glycans in mpi morphants. These deficiencies resulted in 50% embryonic lethality by 4 dpf. Multi-systemic abnormalities, including small eyes, dysmorphic jaws, pericardial edema, a small liver and curled tails, occurred in 82% of the surviving larvae. Importantly, these phenotypes could be rescued with mannose supplementation. Thus, parallel processes in fish and humans contribute to the phenotypes caused by Mpi depletion. Interestingly, mannose was only effective if provided prior to 24 hpf. These data provide insight into treatment efficacy

  3. Small RNA profiling reveals phosphorus deficiency as a contributing factor in symptom expression for citrus huanglongbing disease.

    Science.gov (United States)

    Zhao, Hongwei; Sun, Ruobai; Albrecht, Ute; Padmanabhan, Chellappan; Wang, Airong; Coffey, Michael D; Girke, Thomas; Wang, Zonghua; Close, Timothy J; Roose, Mikeal; Yokomi, Raymond K; Folimonova, Svetlana; Vidalakis, Georgios; Rouse, Robert; Bowman, Kim D; Jin, Hailing

    2013-03-01

    Huanglongbing (HLB) is a devastating citrus disease that is associated with bacteria of the genus 'Candidatus Liberibacter' (Ca. L.). Powerful diagnostic tools and management strategies are desired to control HLB. Host small RNAs (sRNA) play a vital role in regulating host responses to pathogen infection and are used as early diagnostic markers for many human diseases, including cancers. To determine whether citrus sRNAs regulate host responses to HLB, sRNAs were profiled from Citrus sinensis 10 and 14 weeks post grafting with Ca. L. asiaticus (Las)-positive or healthy tissue. Ten new microRNAs (miRNAs), 76 conserved miRNAs, and many small interfering RNAs (siRNAs) were discovered. Several miRNAs and siRNAs were highly induced by Las infection, and can be potentially developed into early diagnosis markers of HLB. miR399, which is induced by phosphorus starvation in other plant species, was induced specifically by infection of Las but not Spiroplasma citri that causes citrus stubborn-a disease with symptoms similar to HLB. We found a 35% reduction of phosphorus in Las-positive citrus trees compared to healthy trees. Applying phosphorus oxyanion solutions to HLB-positive sweet orange trees reduced HLB symptom severity and significantly improved fruit production during a 3-year field trial in south-west Florida. Our molecular, physiological, and field data suggest that phosphorus deficiency is linked to HLB disease symptomology.

  4. ACL deficient potential copers and non-copers reveal different isokinetic quadriceps strength profiles in the early stage after injury

    Science.gov (United States)

    Eitzen, I; Eitzen, TJ; Holm, I; Snyder-Mackler, L; Risberg, MA

    2011-01-01

    Background Isokinetic muscle strength tests using the peak torque value is the most frequently included quadriceps muscle strength measurement for anterior cruciate ligament (ACL) injured subjects. Aims The purpose of this study was to investigate quadriceps muscle performance during the whole isokinetic curve in ACL deficient subjects classified as potential copers or non-copers, and investigate whether these curve profiles were associated with single-leg hop performance. We hypothesized that quadriceps muscle torque at other knee flexion angles than peak torque would give more information about quadriceps muscle strength deficits. Furthermore, we hypothesized that there would be significant torque differences between potential copers and non-copers, and a significant relationship between angle specific torque values and single-leg hop performance. Study Design Cross-sectional study; Level of evidence, 2 Methods Seventy-six individuals with a complete unilateral ACL rupture within the last 3 months were included. The subjects were classified into potential copers and non-copers according to the criteria from Fitzgerald et al12. Isokinetic quadriceps muscle tests were performed at 60°/sec (Biodex 6000). Mean torque values were calculated for peak torque as well as for specific knee flexion angles. The one-leg hop and the 6 meter timed hop tests were included and symmetry indices were used. Results The peak torque value did not identify the largest quadriceps muscle strength deficit. Rather, these were established at knee flexion angles of less than 40°. There were significant differences in angle specific torque values between potential copers and non-copers (p<0.05). Moderate to strong associations were disclosed between angle specific torque values and single-leg hop performance, but only for non-copers (r≥0.32– 0.58). Conclusions Angle specific quadriceps muscle torque values of less than 40° of knee flexion provide more information on the quadriceps

  5. Storage Pool Deficiencies

    Science.gov (United States)

    ... Deficiency Factor V Deficiency Combined FV & FVIII Deficiencies Factor VII Deficiency Factor X Deficiency Factor XI Deficiency Factor ... Deficiency Factor V Deficiency Combined FV & FVIII Deficiencies Factor VII Deficiency Factor X Deficiency Factor XI Deficiency Factor ...

  6. A novel mouse model reveals that polycystin-1 deficiency in ependyma and choroid plexus results in dysfunctional cilia and hydrocephalus.

    Directory of Open Access Journals (Sweden)

    Claas Wodarczyk

    2009-09-01

    Full Text Available Polycystin-1 (PC-1, the product of the PKD1 gene, mutated in the majority of cases of Autosomal Dominant Polycystic Kidney Disease (ADPKD, is a very large (approximately 520 kDa plasma membrane receptor localized in several subcellular compartments including cell-cell/matrix junctions as well as cilia. While heterologous over-expression systems have allowed identification of several of the potential biological roles of this receptor, its precise function remains largely elusive. Studying PC-1 in vivo has been a challenging task due to its complexity and low expression levels. To overcome these limitations and facilitate the study of endogenous PC-1, we have inserted HA- or Myc-tag sequences into the Pkd1 locus by homologous recombination. Here, we show that our approach was successful in generating a fully functional and easily detectable endogenous PC-1. Characterization of PC-1 distribution in vivo showed that it is expressed ubiquitously and is developmentally-regulated in most tissues. Furthermore, our novel tool allowed us to investigate the role of PC-1 in brain, where the protein is abundantly expressed. Subcellular localization of PC-1 revealed strong and specific staining in ciliated ependymal and choroid plexus cells. Consistent with this distribution, we observed hydrocephalus formation both in the ubiquitous knock-out embryos and in newborn mice with conditional inactivation of the Pkd1 gene in the brain. Both choroid plexus and ependymal cilia were morphologically normal in these mice, suggesting a role for PC-1 in ciliary function or signalling in this compartment, rather than in ciliogenesis. We propose that the role of PC-1 in the brain cilia might be to prevent hydrocephalus, a previously unrecognized role for this receptor and one that might have important implications for other genetic or sporadic diseases.

  7. Structural analysis of eight novel and 112 previously reported missense mutations in the interactive FXI mutation database reveals new insight on FXI deficiency.

    Science.gov (United States)

    Saunders, Rebecca E; Shiltagh, Nuha; Gomez, Keith; Mellars, Gillian; Cooper, Carolyn; Perry, David J; Tuddenham, Edward G; Perkins, Stephen J

    2009-08-01

    Factor XI (FXI) functions in blood coagulation. FXI is composed of four apple (Ap) domains and a serine protease (SP) domain. Deficiency of FXI leads to an injury-related bleeding disorder, which is remarkable for the lack of correlation between bleeding symptoms and FXI coagulant activity (FXI:C). The number of mutations previously reported in our interactive web database (http://www.FactorXI.org) is now significantly increased to 183 through our new patient studies and from literature surveys. Eight novel missense mutations give a total of 120 throughout the FXI gene (F11). The most abundant defects in FXI are revealed to be those from low-protein plasma levels (Type I: CRM-) that originate from protein misfolding, rather than from functional defects (Type II: CRM+). A total of 70 Ap missense mutations were analysed using a consensus Ap domain structure generated from the FXI dimer crystal structure. This showed that all parts of the Ap domain were affected. The 47 SP missense mutations were also distributed throughout the SP domain structure. The periphery of the Ap beta-sheet structure is sensitive to structural perturbation caused by residue changes throughout the Ap domain, yet this beta-sheet is crucial for FXI dimer formation. Residues located at the Ap4:Ap4 interface in the dimer are much less directly involved. We conclude that the abundance of Type I defects in FXI results from the sensitivity of the Ap domain folding to residue changes within this, and discuss how structural knowledge of the mutations improves our understanding of FXI deficiencies.

  8. Carnitine Deficiency and Pregnancy

    Directory of Open Access Journals (Sweden)

    Anouk de Bruyn

    2015-01-01

    Full Text Available We present two cases of carnitine deficiency in pregnancy. In our first case, systematic screening revealed L-carnitine deficiency in the first born of an asymptomatic mother. In the course of her second pregnancy, maternal carnitine levels showed a deficiency as well. In a second case, a mother known with carnitine deficiency under supplementation was followed throughout her pregnancy. Both pregnancies had an uneventful outcome. Because carnitine deficiency can have serious complications, supplementation with carnitine is advised. This supplementation should be continued throughout pregnancy according to plasma concentrations.

  9. Single-cell transcriptomic reconstruction reveals cell cycle and multi-lineage differentiation defects in Bcl11a-deficient hematopoietic stem cells.

    Science.gov (United States)

    Tsang, Jason C H; Yu, Yong; Burke, Shannon; Buettner, Florian; Wang, Cui; Kolodziejczyk, Aleksandra A; Teichmann, Sarah A; Lu, Liming; Liu, Pentao

    2015-09-21

    Hematopoietic stem cells (HSCs) are a rare cell type with the ability of long-term self-renewal and multipotency to reconstitute all blood lineages. HSCs are typically purified from the bone marrow using cell surface markers. Recent studies have identified significant cellular heterogeneities in the HSC compartment with subsets of HSCs displaying lineage bias. We previously discovered that the transcription factor Bcl11a has critical functions in the lymphoid development of the HSC compartment. In this report, we employ single-cell transcriptomic analysis to dissect the molecular heterogeneities in HSCs. We profile the transcriptomes of 180 highly purified HSCs (Bcl11a (+/+) and Bcl11a (-/-)). Detailed analysis of the RNA-seq data identifies cell cycle activity as the major source of transcriptomic variation in the HSC compartment, which allows reconstruction of HSC cell cycle progression in silico. Single-cell RNA-seq profiling of Bcl11a (-/-) HSCs reveals abnormal proliferative phenotypes. Analysis of lineage gene expression suggests that the Bcl11a (-/-) HSCs are constituted of two distinct myeloerythroid-restricted subpopulations. Remarkably, similar myeloid-restricted cells could also be detected in the wild-type HSC compartment, suggesting selective elimination of lymphoid-competent HSCs after Bcl11a deletion. These defects are experimentally validated in serial transplantation experiments where Bcl11a (-/-) HSCs are myeloerythroid-restricted and defective in self-renewal. Our study demonstrates the power of single-cell transcriptomics in dissecting cellular process and lineage heterogeneities in stem cell compartments, and further reveals the molecular and cellular defects in the Bcl11a-deficient HSC compartment.

  10. Effects of Fe and Mn deficiencies on the protein profiles of tomato (Solanum lycopersicum) xylem sap as revealed by shotgun analyses.

    Science.gov (United States)

    Ceballos-Laita, Laura; Gutierrez-Carbonell, Elain; Takahashi, Daisuke; Abadía, Anunciación; Uemura, Matsuo; Abadía, Javier; López-Millán, Ana Flor

    2018-01-06

    The aim of this work was to study the effects of Fe and Mn deficiencies on the xylem sap proteome of tomato using a shotgun proteomic approach, with the final goal of elucidating plant response mechanisms to these stresses. This approach yielded 643 proteins reliably identified and quantified with 70% of them predicted as secretory. Iron and Mn deficiencies caused statistically significant and biologically relevant abundance changes in 119 and 118 xylem sap proteins, respectively. In both deficiencies, metabolic pathways most affected were protein metabolism, stress/oxidoreductases and cell wall modifications. First, results suggest that Fe deficiency elicited more stress responses than Mn deficiency, based on the changes in oxidative and proteolytic enzymes. Second, both nutrient deficiencies affect the secondary cell wall metabolism, with changes in Fe deficiency occurring via peroxidase activity, and in Mn deficiency involving peroxidase, Cu-oxidase and fasciclin-like arabinogalactan proteins. Third, the primary cell wall metabolism was affected by both nutrient deficiencies, with changes following opposite directions as judged from the abundances of several glycoside-hydrolases with endo-glycolytic activities and pectin esterases. Fourth, signaling pathways via xylem involving CLE and/or lipids as well as changes in phosphorylation and N-glycosylation also play a role in the responses to these stresses. Biological significance In spite of being essential for the delivery of nutrients to the shoots, our knowledge of xylem responses to nutrient deficiencies is very limited. The present work applies a shotgun proteomic approach to unravel the effects of Fe and Mn deficiencies on the xylem sap proteome. Overall, Fe deficiency seems to elicit more stress in the xylem sap proteome than Mn deficiency, based on the changes measured in proteolytic and oxido-reductase proteins, whereas both nutrients exert modifications in the composition of the primary and secondary

  11. Zinc and the iron donor frataxin regulate oligomerization of the scaffold protein to form new Fe-S cluster assembly centers.

    Science.gov (United States)

    Galeano, B K; Ranatunga, W; Gakh, O; Smith, D Y; Thompson, J R; Isaya, G

    2017-06-21

    Early studies of the bacterial Fe-S cluster assembly system provided structural details for how the scaffold protein and the cysteine desulfurase interact. This work and additional work on the yeast and human systems elucidated a conserved mechanism for sulfur donation but did not provide any conclusive insights into the mechanism for iron delivery from the iron donor, frataxin, to the scaffold. We previously showed that oligomerization is a mechanism by which yeast frataxin (Yfh1) can promote assembly of the core machinery for Fe-S cluster synthesis both in vitro and in cells, in such a manner that the scaffold protein, Isu1, can bind to Yfh1 independent of the presence of the cysteine desulfurase, Nfs1. Here, in the absence of Yfh1, Isu1 was found to exist in two forms, one mostly monomeric with limited tendency to dimerize, and one with a strong propensity to oligomerize. Whereas the monomeric form is stabilized by zinc, the loss of zinc promotes formation of dimer and higher order oligomers. However, upon binding to oligomeric Yfh1, both forms take on a similar symmetrical trimeric configuration that places the Fe-S cluster coordinating residues of Isu1 in close proximity of iron-binding residues of Yfh1. This configuration is suitable for docking of Nfs1 in a manner that provides a structural context for coordinate iron and sulfur donation to the scaffold. Moreover, distinct structural features suggest that in physiological conditions the zinc-regulated abundance of monomeric vs. oligomeric Isu1 yields [Yfh1]·[Isu1] complexes with different Isu1 configurations that afford unique functional properties for Fe-S cluster assembly and delivery.

  12. A novel motion analysis approach reveals late recovery in C57BL/6 mice and deficits in NCAM-deficient mice after sciatic nerve crush.

    Science.gov (United States)

    Fey, Andreas; Schachner, Melitta; Irintchev, Andrey

    2010-05-01

    Assessment of motor abilities after sciatic nerve injury in rodents, in particular mice, relies exclusively on walking track (footprint) analysis despite known limitations of this method. Using principles employed recently for video-based motion analyses after femoral nerve and spinal cord injuries, we have designed and report here a novel approach for functional assessments after sciatic nerve lesions in mice. Functional deficits are estimated by angle and distance measurements on single video frames recorded during beam-walking and inclined ladder climbing. Analyses of adult C57BL/6J mice after crush of the sciatic, tibial, or peroneal nerve allowed the identification of six numerical parameters, detecting impairments of the plantar flexion of the foot and the toe spread. Some of these parameters, as well as footprint functional indices, revealed severe impairment after crush injury of the sciatic or tibial, but not the peroneal nerve, and complete recovery within 3 weeks after lesion. Other novel estimates, however, showed that complete recovery is reached as late as 2-3 months after sciatic nerve crush. These measures detected both tibial and peroneal dysfunction. In contrast to the complete restoration of function in wild-type mice (100%), our new parameters, in contrast to the sciatic functional index, showed incomplete recovery (85%) 90 days after sciatic nerve crush in mice deficient in the neural cell adhesion molecule (NCAM). We conclude that the novel video-based approach is more precise, sensitive, and versatile than established tests, allowing objective numerical assessment of different motor functions in a sciatic nerve injury paradigm in mice.

  13. Iodine Deficiency

    Science.gov (United States)

    ... Fax/Phone Home » Iodine Deficiency Leer en Español Iodine Deficiency Iodine is an element that is needed ... world’s population remains at risk for iodine deficiency. Iodine Deficiency FAQs WHAT IS THE THYROID GLAND? The ...

  14. Global mRNA expression analysis in myosin II deficient strains of Saccharomyces cerevisiae reveals an impairment of cell integrity functions

    Directory of Open Access Journals (Sweden)

    Rivera-Molina Félix E

    2008-01-01

    Full Text Available Abstract Background The Saccharomyces cerevisiae MYO1 gene encodes the myosin II heavy chain (Myo1p, a protein required for normal cytokinesis in budding yeast. Myo1p deficiency in yeast (myo1Δ causes a cell separation defect characterized by the formation of attached cells, yet it also causes abnormal budding patterns, formation of enlarged and elongated cells, increased osmotic sensitivity, delocalized chitin deposition, increased chitin synthesis, and hypersensitivity to the chitin synthase III inhibitor Nikkomycin Z. To determine how differential expression of genes is related to these diverse cell wall phenotypes, we analyzed the global mRNA expression profile of myo1Δ strains. Results Global mRNA expression profiles of myo1Δ strains and their corresponding wild type controls were obtained by hybridization to yeast oligonucleotide microarrays. Results for selected genes were confirmed by real time RT-PCR. A total of 547 differentially expressed genes (p ≤ 0.01 were identified with 263 up regulated and 284 down regulated genes in the myo1Δ strains. Gene set enrichment analysis revealed the significant over-representation of genes in the protein biosynthesis and stress response categories. The SLT2/MPK1 gene was up regulated in the microarray, and a myo1Δslt2Δ double mutant was non-viable. Overexpression of ribosomal protein genes RPL30 and RPS31 suppressed the hypersensitivity to Nikkomycin Z and increased the levels of phosphorylated Slt2p in myo1Δ strains. Increased levels of phosphorylated Slt2p were also observed in wild type strains under these conditions. Conclusion Following this analysis of global mRNA expression in yeast myo1Δ strains, we conclude that 547 genes were differentially regulated in myo1Δ strains and that the stress response and protein biosynthesis gene categories were coordinately regulated in this mutant. The SLT2/MPK1 gene was confirmed to be essential for myo1Δ strain viability, supporting that the up

  15. An RNA-Seq Transcriptome Analysis of Orthophosphate-Deficient White Lupin Reveals Novel Insights into Phosphorus Acclimation in Plants1[W][OA

    Science.gov (United States)

    O’Rourke, Jamie A.; Yang, S. Samuel; Miller, Susan S.; Bucciarelli, Bruna; Liu, Junqi; Rydeen, Ariel; Bozsoki, Zoltan; Uhde-Stone, Claudia; Tu, Zheng Jin; Allan, Deborah; Gronwald, John W.; Vance, Carroll P.

    2013-01-01

    Phosphorus, in its orthophosphate form (Pi), is one of the most limiting macronutrients in soils for plant growth and development. However, the whole-genome molecular mechanisms contributing to plant acclimation to Pi deficiency remain largely unknown. White lupin (Lupinus albus) has evolved unique adaptations for growth in Pi-deficient soils, including the development of cluster roots to increase root surface area. In this study, we utilized RNA-Seq technology to assess global gene expression in white lupin cluster roots, normal roots, and leaves in response to Pi supply. We de novo assembled 277,224,180 Illumina reads from 12 complementary DNA libraries to build what is to our knowledge the first white lupin gene index (LAGI 1.0). This index contains 125,821 unique sequences with an average length of 1,155 bp. Of these sequences, 50,734 were transcriptionally active (reads per kilobase per million reads ≥ 3), representing approximately 7.8% of the white lupin genome, using the predicted genome size of Lupinus angustifolius as a reference. We identified a total of 2,128 sequences differentially expressed in response to Pi deficiency with a 2-fold or greater change and P ≤ 0.05. Twelve sequences were consistently differentially expressed due to Pi deficiency stress in three species, Arabidopsis (Arabidopsis thaliana), potato (Solanum tuberosum), and white lupin, making them ideal candidates to monitor the Pi status of plants. Additionally, classic physiological experiments were coupled with RNA-Seq data to examine the role of cytokinin and gibberellic acid in Pi deficiency-induced cluster root development. This global gene expression analysis provides new insights into the biochemical and molecular mechanisms involved in the acclimation to Pi deficiency. PMID:23197803

  16. Analyses of Selenotranscriptomes and Selenium Concentrations in Response to Dietary Selenium Deficiency and Age Reveal Common and Distinct Patterns by Tissue and Sex in Telomere-Dysfunctional Mice.

    Science.gov (United States)

    Cao, Lei; Zhang, Li; Zeng, Huawei; Wu, Ryan Ty; Wu, Tung-Lung; Cheng, Wen-Hsing

    2017-10-01

    Background: The hierarchies of tissue selenium distribution and selenotranscriptomes are thought to critically affect healthspan and longevity. Objective: We determined selenium status and selenotranscriptomes in response to long-term dietary selenium deficiency and age in tissues of male and female mice. Methods: Weanling telomerase RNA component knockout C57BL/6 mice were fed a selenium-deficient (0.03 mg Se/kg) Torula yeast-based AIN-93G diet or a diet supplemented with sodium selenate (0.15 mg Se/kg) until age 18 or 24 mo. Plasma, hearts, kidneys, livers, and testes were collected to assay for selenotranscriptomes, selected selenoproteins, and tissue selenium concentrations. Data were analyzed with the use of 2-factor ANOVA (diet × age) in both sexes. Results: Dietary selenium deficiency decreased ( P ≤ 0.05) selenium concentrations (65-72%) and glutathione peroxidase (GPX) 3 (82-94%) and selenoprotein P (SELENOP) (17-41%) levels in the plasma of both sexes of mice and mRNA levels (9-68%) of 4, 4, and 12 selenoproteins in the heart, kidney, and liver of males, respectively, and 5, 16, and 14 selenoproteins, respectively, in females. Age increased selenium concentrations and SELENOP levels (27% and 30%, respectively; P ≤ 0.05) in the plasma of males only but decreased (12-46%; P selenium deficiency and age in ≥1 tissue or sex, or both. Dietary selenium deficiency upregulated (40-160%; P ≤ 0.05) iodothyronine deiodinase 2 ( Dio2 ) and selenoprotein N ( Selenon ) in the kidneys of males. Age upregulated (11-44%; P selenium status and selenotranscriptomes because of dietary selenium deficiency and age. © 2017 American Society for Nutrition.

  17. Effects of Fe and Mn deficiencies on the protein profiles of tomato (Solanum lycopersicum) xylem sap as revealed by shotgun analyses

    Science.gov (United States)

    The aim of this work was to study the effects of Fe and Mn deficiencies on the xylem sap proteome of tomato using a shotgun proteomic approach, with the final goal of elucidating plant response mechanisms to these stresses. This approach yielded 643 proteins reliably identified and quantified with 7...

  18. Health Deficiencies

    Data.gov (United States)

    U.S. Department of Health & Human Services — A list of all health deficiencies currently listed on Nursing Home Compare, including the nursing home that received the deficiency, the associated inspection date,...

  19. Proteomic analysis of Arabidopsis thaliana leaves in response to acute boron deficiency and toxicity reveals effects on photosynthesis, carbohydrate metabolism, and protein synthesis.

    Science.gov (United States)

    Chen, Mei; Mishra, Sasmita; Heckathorn, Scott A; Frantz, Jonathan M; Krause, Charles

    2014-02-15

    Boron (B) stress (deficiency and toxicity) is common in plants, but as the functions of this essential micronutrient are incompletely understood, so too are the effects of B stress. To investigate mechanisms underlying B stress, we examined protein profiles in leaves of Arabidopsis thaliana plants grown under normal B (30 μM), compared to plants transferred for 60 and 84 h (i.e., before and after initial visible symptoms) in deficient (0 μM) or toxic (3 mM) levels of B. B-responsive polypeptides were sequenced by mass spectrometry, following 2D gel electrophoresis, and 1D gels and immunoblotting were used to confirm the B-responsiveness of some of these proteins. Fourteen B-responsive proteins were identified, including: 9 chloroplast proteins, 6 proteins of photosynthetic/carbohydrate metabolism (rubisco activase, OEC23, photosystem I reaction center subunit II-1, ATPase δ-subunit, glycolate oxidase, fructose bisphosphate aldolase), 6 stress proteins, and 3 proteins involved in protein synthesis (note that the 14 proteins may fall into multiple categories). Most (8) of the B-responsive proteins decreased under both B deficiency and toxicity; only 3 increased with B stress. Boron stress decreased, or had no effect on, 3 of 4 oxidative stress proteins examined, and did not affect total protein. Hence, our results indicate relatively early specific effects of B stress on chloroplasts and protein synthesis. Copyright © 2013 Elsevier GmbH. All rights reserved.

  20. Co-precipitation of phosphate and iron limits mitochondrial phosphate availability in Saccharomyces cerevisiae lacking the yeast frataxin homologue (YFH1).

    Science.gov (United States)

    Seguin, Alexandra; Santos, Renata; Pain, Debkumar; Dancis, Andrew; Camadro, Jean-Michel; Lesuisse, Emmanuel

    2011-02-25

    Saccharomyces cerevisiae cells lacking the yeast frataxin homologue (Δyfh1) accumulate iron in the mitochondria in the form of nanoparticles of ferric phosphate. The phosphate content of Δyfh1 mitochondria was higher than that of wild-type mitochondria, but the proportion of mitochondrial phosphate that was soluble was much lower in Δyfh1 cells. The rates of phosphate and iron uptake in vitro by isolated mitochondria were higher for Δyfh1 than wild-type mitochondria, and a significant proportion of the phosphate and iron rapidly became insoluble in the mitochondrial matrix, suggesting co-precipitation of these species after oxidation of iron by oxygen. Increasing the amount of phosphate in the medium decreased the amount of iron accumulated by Δyfh1 cells and improved their growth in an iron-dependent manner, and this effect was mostly transcriptional. Overexpressing the major mitochondrial phosphate carrier, MIR1, slightly increased the concentration of soluble mitochondrial phosphate and significantly improved various mitochondrial functions (cytochromes, [Fe-S] clusters, and respiration) in Δyfh1 cells. We conclude that in Δyfh1 cells, soluble phosphate is limiting, due to its co-precipitation with iron.

  1. Insertional mutagenesis in mice deficient for p15Ink4b, p16Ink4a, p21Cip1, and p27Kip1 reveals cancer gene interactions and correlations with tumor phenotypes

    DEFF Research Database (Denmark)

    Kool, Jaap; Uren, Anthony G; Martins, Carla P

    2010-01-01

    -throughput murine leukemia virus insertional mutagenesis screens in mice that are deficient for one or two CDK inhibitors. We retrieved 9,117 retroviral insertions from 476 lymphomas to define hundreds of loci that are mutated more frequently than expected by chance. Many of these loci are skewed toward a specific...... revealed a significant overlap between the datasets. Together, our findings highlight the importance of genetic context within large-scale mutation detection studies, and they show a novel use for insertional mutagenesis data in prioritizing disease-associated genes that emerge from genome-wide association...

  2. Structural characterization of a mixed-linkage glucan deficient mutant reveals alteration in cellulose microfibril orientation in rice coleoptile mesophyll cell walls

    Directory of Open Access Journals (Sweden)

    Andreia Michelle Smith-Moritz

    2015-08-01

    Full Text Available The CELLULOSE SYNTHASE-LIKE F6 (CslF6 gene was previously shown to mediate the biosynthesis of mixed-linkage glucan (MLG, a cell wall polysaccharide that is hypothesized to be a tightly associated with cellulose and also have a role in cell expansion in the primary cell wall of young seedlings in grass species. We have recently shown that loss-of-function cslf6 rice mutants do not accumulate MLG in most vegetative tissues. Despite the absence of a structurally important polymer, MLG, these mutants are unexpectedly viable and only show a moderate growth compromise compared to wild type. Therefore these mutants are ideal biological systems to test the current grass cell wall model. In order to gain a better understanding of the role of MLG in the primary wall, we performed in-depth compositional and structural analyses of the cell walls of three day-old rice seedlings using various biochemical and novel microspectroscopic approaches. We found that cellulose content as well as matrix polysaccharide composition was not significantly altered in the MLG deficient mutant. However, we observed a significant change in cellulose microfibril bundle organization in mesophyll cell walls of the cslf6 mutant. Using synchrotron source Fourier Transform Mid-Infrared Spectromicroscopy for high-resolution imaging, we determined that the bonds associated with cellulose and arabinoxylan, another major component of the primary cell was of grasses, were in a lower energy configuration compared to wild type, suggesting a slightly weaker primary wall in MLG deficient mesophyll cells. Taken together, these results suggest that MLG may influence cellulose deposition in mesophyll cell walls without significantly affecting anisotropic growth thus challenging MLG importance in cell wall expansion.

  3. Iodine Deficiency

    NARCIS (Netherlands)

    Zimmermann, M.B.

    2009-01-01

    Iodine deficiency has multiple adverse effects in humans, termed iodine deficiency disorders, due to inadequate thyroid hormone production. Globally, it is estimated that 2 billion individuals have an insufficient iodine intake, and South Asia and sub-Saharan Africa are particularly affected.

  4. Analysis of meiosis in SUN1 deficient mice reveals a distinct role of SUN2 in mammalian meiotic LINC complex formation and function.

    Directory of Open Access Journals (Sweden)

    Jana Link

    2014-02-01

    Full Text Available LINC complexes are evolutionarily conserved nuclear envelope bridges, composed of SUN (Sad-1/UNC-84 and KASH (Klarsicht/ANC-1/Syne/homology domain proteins. They are crucial for nuclear positioning and nuclear shape determination, and also mediate nuclear envelope (NE attachment of meiotic telomeres, essential for driving homolog synapsis and recombination. In mice, SUN1 and SUN2 are the only SUN domain proteins expressed during meiosis, sharing their localization with meiosis-specific KASH5. Recent studies have shown that loss of SUN1 severely interferes with meiotic processes. Absence of SUN1 provokes defective telomere attachment and causes infertility. Here, we report that meiotic telomere attachment is not entirely lost in mice deficient for SUN1, but numerous telomeres are still attached to the NE through SUN2/KASH5-LINC complexes. In Sun1(-/- meiocytes attached telomeres retained the capacity to form bouquet-like clusters. Furthermore, we could detect significant numbers of late meiotic recombination events in Sun1(-/- mice. Together, this indicates that even in the absence of SUN1 telomere attachment and their movement within the nuclear envelope per se can be functional.

  5. Skeletal muscle microRNA and messenger RNA profiling in cofilin-2 deficient mice reveals cell cycle dysregulation hindering muscle regeneration.

    Directory of Open Access Journals (Sweden)

    Sarah U Morton

    Full Text Available Congenital myopathies are rare skeletal muscle diseases presenting in early age with hypotonia and weakness often linked to a genetic defect. Mutations in the gene for cofilin-2 (CFL2 have been identified in several families as a cause of congenital myopathy with nemaline bodies and cores. Here we explore the global messenger and microRNA expression patterns in quadriceps muscle samples from cofillin-2-null mice and compare them with sibling-matched wild-type mice to determine the molecular pathways and mechanisms involved. Cell cycle processes are markedly dysregulated, with altered expression of genes involved in mitotic spindle formation, and evidence of loss of cell cycle checkpoint regulation. Importantly, alterations in cell cycle, apoptosis and proliferation pathways are present in both mRNA and miRNA expression patterns. Specifically, p21 transcript levels were increased, and the expression of p21 targets, such as cyclin D and cyclin E, was decreased. We therefore hypothesize that deficiency of cofilin-2 is associated with interruption of the cell cycle at several checkpoints, hindering muscle regeneration. Identification of these pathways is an important step towards developing appropriate therapies against various congenital myopathies.

  6. Gene Transfer of Brain-derived Neurotrophic Factor (BDNF) Prevents Neurodegeneration Triggered by FXN Deficiency.

    Science.gov (United States)

    Katsu-Jiménez, Yurika; Loría, Frida; Corona, Juan Carlos; Díaz-Nido, Javier

    2016-05-01

    Friedreich's ataxia is a predominantly neurodegenerative disease caused by recessive mutations that produce a deficiency of frataxin (FXN). Here, we have used a herpesviral amplicon vector carrying a gene encoding for brain-derived neurotrophic factor (BDNF) to drive its overexpression in neuronal cells and test for its effect on FXN-deficient neurons both in culture and in the mouse cerebellum in vivo. Gene transfer of BDNF to primary cultures of mouse neurons prevents the apoptosis which is triggered by the knockdown of FXN gene expression. This neuroprotective effect of BDNF is also observed in vivo in a viral vector-based knockdown mouse cerebellar model. The injection of a lentiviral vector carrying a minigene encoding for a FXN-specific short hairpin ribonucleic acid (shRNA) into the mouse cerebellar cortex triggers a FXN deficit which is accompanied by significant apoptosis of granule neurons as well as loss of calbindin in Purkinje cells. These pathological changes are accompanied by a loss of motor coordination of mice as assayed by the rota-rod test. Coinjection of a herpesviral vector encoding for BDNF efficiently prevents both the development of cerebellar neuropathology and the ataxic phenotype. These data demonstrate the potential therapeutic usefulness of neurotrophins like BDNF to protect FXN-deficient neurons from degeneration.

  7. Mapping of a Cellulose-Deficient Mutant Named dwarf1-1 in Sorghum bicolor to the Green Revolution Gene gibberellin20-oxidase Reveals a Positive Regulatory Association between Gibberellin and Cellulose Biosynthesis.

    Science.gov (United States)

    Petti, Carloalberto; Hirano, Ko; Stork, Jozsef; DeBolt, Seth

    2015-09-01

    Here, we show a mechanism for expansion regulation through mutations in the green revolution gene gibberellin20 (GA20)-oxidase and show that GAs control biosynthesis of the plants main structural polymer cellulose. Within a 12,000 mutagenized Sorghum bicolor plant population, we identified a single cellulose-deficient and male gametophyte-dysfunctional mutant named dwarf1-1 (dwf1-1). Through the Sorghum propinquum male/dwf1-1 female F2 population, we mapped dwf1-1 to a frameshift in GA20-oxidase. Assessment of GAs in dwf1-1 revealed ablation of GA. GA ablation was antagonistic to the expression of three specific cellulose synthase genes resulting in cellulose deficiency and growth dwarfism, which were complemented by exogenous bioactive gibberellic acid application. Using quantitative polymerase chain reaction, we found that GA was positively regulating the expression of a subset of specific cellulose synthase genes. To cross reference data from our mapped Sorghum sp. allele with another monocotyledonous plant, a series of rice (Oryza sativa) mutants involved in GA biosynthesis and signaling were isolated, and these too displayed cellulose deficit. Taken together, data support a model whereby suppressed expansion in green revolution GA genes involves regulation of cellulose biosynthesis. © 2015 American Society of Plant Biologists. All Rights Reserved.

  8. Antepartum Ornithine Transcarbamylase Deficiency

    Directory of Open Access Journals (Sweden)

    Hitoshi Nakajima

    2014-11-01

    Full Text Available Ornithine transcarbamylase deficiency (OTCD is the most common type urea cycle enzyme deficiencies. This syndrome results from a deficiency of the mitochondrial enzyme ornithine transcarbamylase, which catalyzes the conversion of ornithine and carbamoyl phosphate to citrullin. Our case was a 28-year-old female diagnosed with OTCD following neurocognitive deficit during her first pregnancy. Although hyperammonemia was suspected as the cause of the patient's mental changes, there was no evidence of chronic liver disease. Plasma amino acid and urine organic acid analysis revealed OTCD. After combined modality treatment with arginine, sodium benzoate and hemodialysis, the patient's plasma ammonia level stabilized and her mental status returned to normal. At last she recovered without any damage left.

  9. Metabolite profiles reveal energy failure and impaired beta-oxidation in liver of mice with complex III deficiency due to a BCS1L mutation.

    Directory of Open Access Journals (Sweden)

    Heike Kotarsky

    Full Text Available BACKGROUND & AIMS: Liver is a target organ in many mitochondrial disorders, especially if the complex III assembly factor BCS1L is mutated. To reveal disease mechanism due to such mutations, we have produced a transgenic mouse model with c.232A>G mutation in Bcs1l, the causative mutation for GRACILE syndrome. The homozygous mice develop mitochondrial hepatopathy with steatosis and fibrosis after weaning. Our aim was to assess cellular mechanisms for disease onset and progression using metabolomics. METHODS: With mass spectrometry we analyzed metabolite patterns in liver samples obtained from homozygotes and littermate controls of three ages. As oxidative stress might be a mechanism for mitochondrial hepatopathy, we also assessed H(2O(2 production and expression of antioxidants. RESULTS: Homozygotes had a similar metabolic profile at 14 days of age as controls, with the exception of slightly decreased AMP. At 24 days, when hepatocytes display first histopathological signs, increases in succinate, fumarate and AMP were found associated with impaired glucose turnover and beta-oxidation. At end stage disease after 30 days, these changes were pronounced with decreased carbohydrates, high levels of acylcarnitines and amino acids, and elevated biogenic amines, especially putrescine. Signs of oxidative stress were present in end-stage disease. CONCLUSIONS: The findings suggest an early Krebs cycle defect with increases of its intermediates, which might play a role in disease onset. During disease progression, carbohydrate and fatty acid metabolism deteriorate leading to a starvation-like condition. The mouse model is valuable for further investigations on mechanisms in mitochondrial hepatopathy and for interventions.

  10. What Are Rare Clotting Factor Deficiencies?

    Science.gov (United States)

    ... Deficiency Factor V Deficiency Combined FV & FVIII Deficiencies Factor VII Deficiency Factor X Deficiency Factor XI Deficiency Factor ... Deficiency Factor V Deficiency Combined FV & FVIII Deficiencies Factor VII Deficiency Factor X Deficiency Factor XI Deficiency Factor ...

  11. Growth hormone receptor-deficient pigs resemble the pathophysiology of human Laron syndrome and reveal altered activation of signaling cascades in the liver.

    Science.gov (United States)

    Hinrichs, Arne; Kessler, Barbara; Kurome, Mayuko; Blutke, Andreas; Kemter, Elisabeth; Bernau, Maren; Scholz, Armin M; Rathkolb, Birgit; Renner, Simone; Bultmann, Sebastian; Leonhardt, Heinrich; de Angelis, Martin Hrabĕ; Nagashima, Hiroshi; Hoeflich, Andreas; Blum, Werner F; Bidlingmaier, Martin; Wanke, Rüdiger; Dahlhoff, Maik; Wolf, Eckhard

    2018-05-01

    Laron syndrome (LS) is a rare, autosomal recessive disorder in humans caused by loss-of-function mutations of the growth hormone receptor (GHR) gene. To establish a large animal model for LS, pigs with GHR knockout (KO) mutations were generated and characterized. CRISPR/Cas9 technology was applied to mutate exon 3 of the GHR gene in porcine zygotes. Two heterozygous founder sows with a 1-bp or 7-bp insertion in GHR exon 3 were obtained, and their heterozygous F1 offspring were intercrossed to produce GHR-KO, heterozygous GHR mutant, and wild-type pigs. Since the latter two groups were not significantly different in any parameter investigated, they were pooled as the GHR expressing control group. The characterization program included body and organ growth, body composition, endocrine and clinical-chemical parameters, as well as signaling studies in liver tissue. GHR-KO pigs lacked GHR and had markedly reduced serum insulin-like growth factor 1 (IGF1) levels and reduced IGF-binding protein 3 (IGFBP3) activity but increased IGFBP2 levels. Serum GH concentrations were significantly elevated compared with control pigs. GHR-KO pigs had a normal birth weight. Growth retardation became significant at the age of five weeks. At the age of six months, the body weight of GHR-KO pigs was reduced by 60% compared with controls. Most organ weights of GHR-KO pigs were reduced proportionally to body weight. However, the weights of liver, kidneys, and heart were disproportionately reduced, while the relative brain weight was almost doubled. GHR-KO pigs had a markedly increased percentage of total body fat relative to body weight and displayed transient juvenile hypoglycemia along with decreased serum triglyceride and cholesterol levels. Analysis of insulin receptor related signaling in the liver of adult fasted pigs revealed increased phosphorylation of IRS1 and PI3K. In agreement with the loss of GHR, phosphorylation of STAT5 was significantly reduced. In contrast, phosphorylation

  12. Growth hormone receptor-deficient pigs resemble the pathophysiology of human Laron syndrome and reveal altered activation of signaling cascades in the liver

    Directory of Open Access Journals (Sweden)

    Arne Hinrichs

    2018-05-01

    Full Text Available Objective: Laron syndrome (LS is a rare, autosomal recessive disorder in humans caused by loss-of-function mutations of the growth hormone receptor (GHR gene. To establish a large animal model for LS, pigs with GHR knockout (KO mutations were generated and characterized. Methods: CRISPR/Cas9 technology was applied to mutate exon 3 of the GHR gene in porcine zygotes. Two heterozygous founder sows with a 1-bp or 7-bp insertion in GHR exon 3 were obtained, and their heterozygous F1 offspring were intercrossed to produce GHR-KO, heterozygous GHR mutant, and wild-type pigs. Since the latter two groups were not significantly different in any parameter investigated, they were pooled as the GHR expressing control group. The characterization program included body and organ growth, body composition, endocrine and clinical-chemical parameters, as well as signaling studies in liver tissue. Results: GHR-KO pigs lacked GHR and had markedly reduced serum insulin-like growth factor 1 (IGF1 levels and reduced IGF-binding protein 3 (IGFBP3 activity but increased IGFBP2 levels. Serum GH concentrations were significantly elevated compared with control pigs. GHR-KO pigs had a normal birth weight. Growth retardation became significant at the age of five weeks. At the age of six months, the body weight of GHR-KO pigs was reduced by 60% compared with controls. Most organ weights of GHR-KO pigs were reduced proportionally to body weight. However, the weights of liver, kidneys, and heart were disproportionately reduced, while the relative brain weight was almost doubled. GHR-KO pigs had a markedly increased percentage of total body fat relative to body weight and displayed transient juvenile hypoglycemia along with decreased serum triglyceride and cholesterol levels. Analysis of insulin receptor related signaling in the liver of adult fasted pigs revealed increased phosphorylation of IRS1 and PI3K. In agreement with the loss of GHR, phosphorylation of STAT5 was

  13. Arginase-1 deficiency.

    Science.gov (United States)

    Sin, Yuan Yan; Baron, Garrett; Schulze, Andreas; Funk, Colin D

    2015-12-01

    Arginase-1 (ARG1) deficiency is a rare autosomal recessive disorder that affects the liver-based urea cycle, leading to impaired ureagenesis. This genetic disorder is caused by 40+ mutations found fairly uniformly spread throughout the ARG1 gene, resulting in partial or complete loss of enzyme function, which catalyzes the hydrolysis of arginine to ornithine and urea. ARG1-deficient patients exhibit hyperargininemia with spastic paraparesis, progressive neurological and intellectual impairment, persistent growth retardation, and infrequent episodes of hyperammonemia, a clinical pattern that differs strikingly from other urea cycle disorders. This review briefly highlights the current understanding of the etiology and pathophysiology of ARG1 deficiency derived from clinical case reports and therapeutic strategies stretching over several decades and reports on several exciting new developments regarding the pathophysiology of the disorder using ARG1 global and inducible knockout mouse models. Gene transfer studies in these mice are revealing potential therapeutic options that can be exploited in the future. However, caution is advised in extrapolating results since the lethal disease phenotype in mice is much more severe than in humans indicating that the mouse models may not precisely recapitulate human disease etiology. Finally, some of the functions and implications of ARG1 in non-urea cycle activities are considered. Lingering questions and future areas to be addressed relating to the clinical manifestations of ARG1 deficiency in liver and brain are also presented. Hopefully, this review will spark invigorated research efforts that lead to treatments with better clinical outcomes.

  14. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Research Home / < Back To Health Topics / Iron-Deficiency Anemia Iron-Deficiency Anemia Also known as Leer en español Iron-deficiency ... iron-deficiency anemia. Blood tests to screen for iron-deficiency anemia To screen for iron-deficiency anemia, your doctor ...

  15. Quantitative mass spectrometry of histones H3.2 and H3.3 in Suz12-deficient mouse embryonic stem cells reveals distinct, dynamic post-translational modifications at Lys-27 and Lys-36

    DEFF Research Database (Denmark)

    Jung, Hye Ryung; Pasini, Diego; Helin, Kristian

    2010-01-01

    distinct coexisting modifications. In certain cases, high mass accuracy LTQ-Orbitrap MS/MS allowed precise localization of near isobaric coexisting PTMs such as trimethylation and acetylation within individual peptides. ETD MS/MS facilitated sequencing and annotation of phosphorylated histone peptides....... The combined use of ETD and CID MS/MS increased the total number of identified modified peptides. Comparative quantitative analysis of histones from wild type and Suz12-deficient ESCs using stable isotope labeling with amino acids in cell culture and LC-MS/MS revealed a dramatic reduction of H3K27me2 and H3K27......me3 and an increase of H3K27ac, thereby uncovering an antagonistic methyl/acetyl switch at H3K27. The reduction in H3K27 methylation and increase in H3K27 acetylation was accompanied by H3K36 acetylation and methylation. Estimation of the global isoform percentage of unmodified and modified histone...

  16. Iron deficiency

    DEFF Research Database (Denmark)

    Schou, Morten; Bosselmann, Helle; Gaborit, Freja

    2015-01-01

    BACKGROUND: Both iron deficiency (ID) and cardiovascular biomarkers are associated with a poor outcome in heart failure (HF). The relationship between different cardiovascular biomarkers and ID is unknown, and the true prevalence of ID in an outpatient HF clinic is probably overlooked. OBJECTIVES.......043). CONCLUSION: ID is frequent in an outpatient HF clinic. ID is not associated with cardiovascular biomarkers after adjustment for traditional confounders. Inflammation, but not neurohormonal activation is associated with ID in systolic HF. Further studies are needed to understand iron metabolism in elderly HF...

  17. Mechanism of the Dual Activities of Human CYP17A1 and Binding to Anti-Prostate Cancer Drug Abiraterone Revealed by a Novel V366M Mutation Causing 17,20 Lyase Deficiency

    Directory of Open Access Journals (Sweden)

    Mónica Fernández-Cancio

    2018-04-01

    Full Text Available The CYP17A1 gene regulates sex steroid biosynthesis in humans through 17α-hydroxylase/17,20 lyase activities and is a target of anti-prostate cancer drug abiraterone. In a 46, XY patient with female external genitalia, together with a loss of function mutation S441P, we identified a novel missense mutation V366M at the catalytic center of CYP17A1 which preferentially impaired 17,20 lyase activity. Kinetic experiments with bacterially expressed proteins revealed that V366M mutant enzyme can bind and metabolize pregnenolone to 17OH-pregnenolone, but 17OH-pregnenolone binding and conversion to dehydroepiandrosterone (DHEA was impaired, explaining the patient’s steroid profile. Abiraterone could not bind and inhibit the 17α-hydroxylase activity of the CYP17A1-V366M mutant. Molecular dynamics (MD simulations showed that V366M creates a “one-way valve” and suggests a mechanism for dual activities of human CYP17A1 where, after the conversion of pregnenolone to 17OH-pregnenolone, the product exits the active site and re-enters for conversion to dehydroepiandrosterone. The V366M mutant also explained the effectiveness of the anti-prostate cancer drug abiraterone as a potent inhibitor of CYP17A1 by binding tightly at the active site in the WT enzyme. The V366M is the first human mutation to be described at the active site of CYP17A1 that causes isolated 17,20 lyase deficiency. Knowledge about the specificity of CYP17A1 activities is of importance for the development of treatments for polycystic ovary syndrome and inhibitors for prostate cancer therapy.

  18. Lipidomics and H218O labeling techniques reveal increased remodeling of DHA-containing membrane phospholipids associated with abnormal locomotor responses in α-tocopherol deficient zebrafish (danio rerio embryos

    Directory of Open Access Journals (Sweden)

    Melissa Q. McDougall

    2016-08-01

    Full Text Available We hypothesized that vitamin E (α-tocopherol is required by the developing embryonic brain to prevent depletion of highly polyunsaturated fatty acids, especially docosahexaenoic acid (DHA, 22:6, the loss of which we predicted would underlie abnormal morphological and behavioral outcomes. Therefore, we fed adult 5D zebrafish (Danio rerio defined diets without (E− or with added α-tocopherol (E+, 500 mg RRR-α-tocopheryl acetate/kg diet for a minimum of 80 days, and then spawned them to obtain E− and E+ embryos. The E− compared with E+ embryos were 82% less responsive (p<0.01 to a light/dark stimulus at 96 h post-fertilization (hpf, demonstrating impaired locomotor behavior, even in the absence of gross morphological defects. Evaluation of phospholipid (PL and lysophospholipid (lyso-PL composition using untargeted lipidomics in E− compared with E+ embryos at 24, 48, 72, and 120 hpf showed that four PLs and three lyso-PLs containing docosahexaenoic acid (DHA, including lysophosphatidylcholine (LPC 22:6, required for transport of DHA into the brain, p<0.001, were at lower concentrations in E− at all time-points. Additionally, H218O labeling experiments revealed enhanced turnover of LPC 22:6 (p<0.001 and three other DHA-containing PLs in the E− compared with the E+ embryos, suggesting that increased membrane remodeling is a result of PL depletion. Together, these data indicate that α-tocopherol deficiency in the zebrafish embryo causes the specific depletion and increased turnover of DHA-containing PL and lyso-PLs, which may compromise DHA delivery to the brain and thereby contribute to the functional impairments observed in E− embryos.

  19. Iron-Deficiency Anemia

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    Full Text Available ... To Health Topics / Iron-Deficiency Anemia Iron-Deficiency Anemia Also known as Leer en español Iron-deficiency ... anemia. Blood tests to screen for iron-deficiency anemia To screen for iron-deficiency anemia, your doctor ...

  20. Iron-Deficiency Anemia

    Science.gov (United States)

    ... To Health Topics / Iron-Deficiency Anemia Iron-Deficiency Anemia Also known as Leer en español Iron-deficiency ... anemia. Blood tests to screen for iron-deficiency anemia To screen for iron-deficiency anemia, your doctor ...

  1. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... you are diagnosed with iron-deficiency anemia. Risk Factors You may have an increased risk for iron- ... iron-deficiency anemia if you have certain risk factors , including pregnancy. To prevent iron-deficiency anemia, your ...

  2. Iron-Deficiency Anemia

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    Full Text Available ... to moderate iron-deficiency anemia, or red blood cell transfusion for severe iron-deficiency anemia. You may ... body needs iron to make healthy red blood cells. Iron-deficiency anemia usually develops over time because ...

  3. Vitamin Deficiency Anemia

    Science.gov (United States)

    ... are unique to specific vitamin deficiencies. Folate-deficiency anemia risk factors include: Undergoing hemodialysis for kidney failure. ... the metabolism of folate. Vitamin B-12 deficiency anemia risk factors include: Lack of intrinsic factor. Most ...

  4. Atypical B12 Deficiency with Nonresolving Paraesthesia

    Directory of Open Access Journals (Sweden)

    S. Haider

    2013-01-01

    Full Text Available Vitamin B12 deficiency can present with various hematological, gastrointestinal and neurological manifestations. We report a case of elderly female who presented with neuropathy and vitamin B12 deficiency where the final work-up revealed polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS. This case suggests that, although POEMS syndrome is a rare entity, it can present with vitamin-B12 deficiency and thus specific work up for early diagnosis of POEMS should be considered in patients with B12 deficiency unresponsive to therapy.

  5. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Iron-Deficiency Anemia Iron-Deficiency Anemia Also known as Leer en español Iron-deficiency anemia is a ... address the cause of your iron deficiency, such as any underlying bleeding. If undiagnosed or untreated, iron- ...

  6. Functional PAK-2 knockout and replacement with a caspase cleavage-deficient mutant in mice reveals differential requirements of full-length PAK-2 and caspase-activated PAK-2p34.

    Science.gov (United States)

    Marlin, Jerry W; Chang, Yu-Wen E; Ober, Margaret; Handy, Amy; Xu, Wenhao; Jakobi, Rolf

    2011-06-01

    p21-Activated protein kinase 2 (PAK-2) has both anti- and pro-apoptotic functions depending on its mechanism of activation. Activation of full-length PAK-2 by the monomeric GTPases Cdc42 or Rac stimulates cell survival, whereas caspase activation of PAK-2 to the PAK-2p34 fragment is involved in the apoptotic response. In this study we use functional knockout of PAK-2 and gene replacement with the caspase cleavage-deficient PAK-2D212N mutant to differentiate the biological functions of full-length PAK-2 and caspase-activated PAK-2p34. Knockout of PAK-2 results in embryonic lethality at early stages before organ development, whereas replacement with the caspase cleavage-deficient PAK-2D212N results in viable and healthy mice, indicating that early embryonic lethality is caused by deficiency of full-length PAK-2 rather than lack of caspase activation to the PAK-2p34 fragment. However, deficiency of caspase activation of PAK-2 decreased spontaneous cell death of primary mouse embryonic fibroblasts and increased cell growth at high cell density. In contrast, stress-induced cell death by treatment with the anti-cancer drug cisplatin was not reduced by deficiency of caspase activation of PAK-2, but switched from an apoptotic to a nonapoptotic, caspase-independent mechanism. Homozygous PAK-2D212N primary mouse embryonic fibroblasts that lack the ability to generate the proapoptotic PAK-2p34 show less activation of the effector caspase 3, 6, and 7, indicating that caspase activation of PAK-2 amplifies the apoptotic response through a positive feedback loop resulting in more activation of effector caspases.

  7. Deficiency of the Chemotactic Factor Inactivator in Human Sera with α1-Antitrypsin Deficiency

    Science.gov (United States)

    Ward, Peter A.; Talamo, Richard C.

    1973-01-01

    As revealed by appropriate fractionation procedures, human serum deficient in α1-antitrypsin (α1-AT) is also deficient in the naturally occurring chemotactic factor inactivator. These serum donors had severe pulmonary emphysema. Serum from patients with clinically similar pulmonary disease, but with presence of α1-AT in the serum, showed no such deficiency of the chemotactic factor inactivator. When normal human serum and α1-AT-deficient human sera are chemotactically activated by incubation with immune precipitates, substantially more chemotactic activity is generated in α1-AT-deficient serum. These data indicate that in α1-AT-deficient serum there is an imbalance in the generation and control of chemotactic factors. It is suggested that the theory regarding development of pulmonary emphysema in patients lacking the α1-antitrypsin in their serum should be modified to take into account a deficiency of the chemotactic factor inactivator. PMID:4683887

  8. The study of the mechanism of arsenite toxicity in respiration-deficient cells reveals that NADPH oxidase-derived superoxide promotes the same downstream events mediated by mitochondrial superoxide in respiration-proficient cells

    Energy Technology Data Exchange (ETDEWEB)

    Guidarelli, Andrea; Fiorani, Mara; Carloni, Silvia; Cerioni, Liana; Balduini, Walter; Cantoni, Orazio, E-mail: orazio.cantoni@uniurb.it

    2016-09-15

    We herein report the results from a comparative study of arsenite toxicity in respiration-proficient (RP) and -deficient (RD) U937 cells. An initial characterization of these cells led to the demonstration that the respiration-deficient phenotype is not associated with apparent changes in mitochondrial mass and membrane potential. In addition, similar levels of superoxide (O{sub 2}{sup .-}) were generated by RP and RD cells in response to stimuli specifically triggering respiratory chain-independent mitochondrial mechanisms or extramitochondrial, NADPH-oxidase dependent, mechanisms. At the concentration of 2.5 μM, arsenite elicited selective formation of O{sub 2}{sup .-} in the respiratory chain of RP cells, with hardly any contribution of the above mechanisms. Under these conditions, O{sub 2}{sup .-} triggered downstream events leading to endoplasmic reticulum (ER) stress, autophagy and apoptosis. RD cells challenged with similar levels of arsenite failed to generate O{sub 2}{sup .-} because of the lack of a functional respiratory chain and were therefore resistant to the toxic effects mediated by the metalloid. Their resistance, however, was lost after exposure to four fold greater concentrations of arsenite, coincidentally with the release of O{sub 2}{sup .-} mediated by NADPH oxidase. Interestingly, extramitochondrial O{sub 2}{sup .-} triggered the same downstream events and an identical mode of death previously observed in RP cells. Taken together, the results obtained in this study indicate that arsenite toxicity is strictly dependent on O{sub 2}{sup .-} availability that, regardless of whether generated in the mitochondrial or extramitochondrial compartments, triggers similar downstream events leading to ER stress, autophagy and apoptosis. - Highlights: • Mitochondrial superoxide mediates arsenite toxicity in respiration-proficient cells. • NADPH-derived superoxide mediates arsenite toxicity in respiration-deficient cells. • Arsenite causes apoptosis

  9. Early transcriptomic changes induced by magnesium deficiency in Arabidopsis thaliana reveal the alteration of circadian clock gene expression in roots and the triggering of abscisic acid-responsive genes.

    Science.gov (United States)

    Hermans, Christian; Vuylsteke, Marnik; Coppens, Frederik; Craciun, Adrian; Inzé, Dirk; Verbruggen, Nathalie

    2010-07-01

    *Plant growth and development ultimately depend on environmental variables such as the availability of essential minerals. Unravelling how nutrients affect gene expression will help to understand how they regulate plant growth. *This study reports the early transcriptomic response to magnesium (Mg) deprivation in Arabidopsis. Whole-genome transcriptome was studied in the roots and young mature leaves 4, 8 and 28 h after the removal of Mg from the nutrient solution. *The highest number of regulated genes was first observed in the roots. Contrary to other mineral deficiencies, Mg depletion did not induce a higher expression of annotated genes in Mg uptake. Remarkable responses include the perturbation of the central oscillator of the circadian clock in roots and the triggering of abscisic acid (ABA) signalling, with half of the up-regulated Mg genes in leaves being ABA-responsive. However, no change in ABA content was observed. *The specificity of the response of some Mg-regulated genes was challenged by studying their expression after other mineral deficiencies and environmental stresses. The possibility to develop markers for Mg incipient deficiency is discussed here.

  10. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... fatigue or tiredness, shortness of breath, or chest pain. If your doctor diagnoses you with iron-deficiency ... Common symptoms of iron-deficiency anemia include: Chest pain Coldness in the hands and feet Difficulty concentrating ...

  11. Iron-Deficiency Anemia

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    Full Text Available ... heart failure . Increased risk of infections Motor or cognitive development delays in children Pregnancy complications, such as ... for iron-deficiency anemia. Learn about exciting research areas that NHLBI is exploring about iron-deficiency anemia. ...

  12. Factor VII deficiency

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000548.htm Factor VII deficiency To use the sharing features on this page, please enable JavaScript. Factor VII (seven) deficiency is a disorder caused by a ...

  13. Iron-Deficiency Anemia

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    Full Text Available ... deficiency anemia can cause serious complications, including heart failure and development delays in children. Explore this Health ... lead to iron-deficiency anemia include: End-stage kidney failure, where there is blood loss during dialysis. ...

  14. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... for iron-deficiency anemia. Lifestyle habits Certain lifestyle habits may increase your risk for iron-deficiency anemia, including: Vegetarian or vegan eating patterns. Not eating enough iron-rich foods, such ...

  15. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... deficiency anemia can cause serious complications, including heart failure and development delays in children. Explore this Health ... to iron-deficiency anemia include: End-stage kidney failure, where there is blood loss during dialysis. People ...

  16. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... view the colon directly. What if my doctor thinks something else is causing my iron-deficiency anemia? ... deficiency anemia early in life affects later behavior, thinking, and mood during adolescence. Treating anemia in premature ...

  17. Iron-Deficiency Anemia

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    Full Text Available ... mg and women need 18 mg. After age 51, both men and women need 8 mg. Pregnant ... for iron-deficiency anemia. Learn about exciting research areas that NHLBI is exploring about iron-deficiency anemia. ...

  18. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron-deficiency anemia. These conditions include: Intestinal and digestive conditions, such as celiac disease; inflammatory bowel diseases, ... iron-deficiency anemia , such as bleeding in the digestive or urinary tract or heavy menstrual bleeding, your ...

  19. Iron-Deficiency Anemia

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    Full Text Available ... conditions that can cause iron-deficiency anemia. Blood tests to screen for iron-deficiency anemia To screen ... the size of your liver and spleen. Blood tests Based on results from blood tests to screen ...

  20. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... from developing iron-deficiency anemia. Foods that are good sources of iron include dried beans, dried fruits, eggs, lean red meat, ... signs of iron-deficiency anemia include: Brittle nails ...

  1. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... your doctor may recommend you eat heart-healthy foods or control other conditions that can cause iron-deficiency anemia. Blood tests to screen for iron-deficiency anemia To screen ...

  2. Fire Safety Deficiencies

    Data.gov (United States)

    U.S. Department of Health & Human Services — A list of all fire safety deficiencies currently listed on Nursing Home Compare, including the nursing home that received the deficiency, the associated inspection...

  3. Iron-Deficiency Anemia

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    Full Text Available ... learning how having iron-deficiency anemia early in life affects later behavior, thinking, and mood during adolescence. ... iron-deficiency anemia in blood donors affects the quality of donated red blood cells, such as how ...

  4. Iron-Deficiency Anemia

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    Full Text Available ... iron-deficiency anemia in blood donors affects the quality of donated red blood cells, such as how ... Cells From Iron-deficient Donors: Recovery and Storage Quality. Learn more about participating in a clinical trial . ...

  5. Iron-Deficiency Anemia

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    Full Text Available ... leaving cells where it is stored or from being absorbed in the duodenum, the first part of ... treatments for iron-deficiency anemia. Living With After being diagnosed with iron-deficiency anemia, it is important ...

  6. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... if you are diagnosed with iron-deficiency anemia. Risk Factors You may have an increased risk for iron-deficiency anemia because of your age, ... or sex. Age You may be at increased risk for iron deficiency at certain ages: Infants between ...

  7. Iron-Deficiency Anemia

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    Full Text Available ... Home / < Back To Health Topics / Iron-Deficiency Anemia Iron-Deficiency Anemia Also known as Leer en español ... bleeding Consuming less than recommended daily amounts of iron Iron-deficiency anemia can be caused by getting ...

  8. Iron-Deficiency Anemia

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    Full Text Available ... Topics News & Resources Intramural Research Home / < Back To Health Topics / Iron-Deficiency Anemia Iron-Deficiency Anemia Also known as Leer ... and symptoms as well as complications from iron-deficiency anemia. Research for Your Health The NHLBI is part of the U.S. Department ...

  9. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... anemia, your doctor may order the following blood tests to diagnose iron-deficiency anemia: Complete blood count (CBC) to ... than normal when viewed under a microscope. Different tests help your doctor diagnose iron-deficiency anemia. In iron-deficiency anemia, blood ...

  10. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... for iron-deficiency anemia if you have certain risk factors , including pregnancy. To prevent iron-deficiency anemia, your doctor may recommend you eat heart-healthy foods or control other conditions that can cause iron-deficiency anemia. ...

  11. Proteomic analysis reveals differential accumulation of small heat shock proteins and late embryogenesis abundant proteins between ABA-deficient mutant vp5 seeds and wild-type Vp5 seeds in maize

    Directory of Open Access Journals (Sweden)

    Xiaolin eWu

    2015-01-01

    Full Text Available ABA is a major plant hormone that plays important roles during many phases of plant life cycle, including seed development, maturity and dormancy, and especially the acquisition of desiccation tolerance. Understanding of the molecular basis of ABA-mediated plant response to stress is of interest not only in basic research on plant adaptation but also in applied research on plant productivity. Maize mutant viviparous-5 (vp5, deficient in ABA biosynthesis in seeds, is a useful material for studying ABA-mediated response in maize. Due to carotenoid deficiency, vp5 endosperm is white, compared to yellow Vp5 endosperm. However, the background difference at proteome level between vp5 and Vp5 seeds is unclear. This study aimed to characterize proteome alterations of maize vp5 seeds and to identify ABA-dependent proteins during seed maturation. We compared the embryo and endosperm proteomes of vp5 and Vp5 seeds by gel-based proteomics. Up to 46 protein spots, most in embryos, were found to be differentially accumulated between vp5 and Vp5. The identified proteins included small heat shock proteins (sHSPs, late embryogenesis abundant (LEA proteins, stress proteins, storage proteins and enzymes among others. However, EMB564, the most abundant LEA protein in maize embryo, accumulated in comparable levels between vp5 and Vp5 embryos, which contrasted to previously characterized, greatly lowered expression of emb564 mRNA in vp5 embryos. Moreover, LEA proteins and sHSPs displayed differential accumulations in vp5 embryos: six out of eight identified LEA proteins decreased while nine sHSPs increased in abundance. Finally, we discussed the possible causes of global proteome alterations, especially the observed differential accumulation of identified LEA proteins and sHSPs in vp5 embryos. The data derived from this study provides new insight into ABA-dependent proteins and ABA-mediated response during maize seed maturation.

  12. Iron-Deficiency Anemia

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    Full Text Available ... increased need for iron during growth spurts. Older adults, especially those over age ... athletes. Athletes, especially young females, are at risk for iron deficiency. Endurance ...

  13. Iodine deficiency disorders

    Energy Technology Data Exchange (ETDEWEB)

    Ali, S M [Pakistan Council for Science and Technology, Islamabad (Pakistan)

    1994-12-31

    Iodine deficiency (IDD) is one of the common problem in the diet. Iodine deficiency as prevalence of goiter in population occurs in the mountainous areas. There is consensus that 800 million people are at risk of IDD from living in iodine deficient area and 190 million from goiter. Very high prevalence of IDD in different parts of the world are striking. It has generally observed that in iodine-deficient areas about 50% are affected with goiter, 1-5% from cretinsim and 20% from impaired mental and/or mortor function. (A.B.).

  14. Iron-Deficiency Anemia

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    Full Text Available ... Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs. Our ... more information about Donor Iron Deficiency Study - Red Blood Cells ...

  15. Iron-Deficiency Anemia

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    Full Text Available ... exploring about iron-deficiency anemia. Read more New treatments for disorders that lead to iron-deficiency anemia. We are ... and other pathways. This could help develop new therapies for conditions that ... behavior, thinking, and mood during adolescence. Treating anemia in ...

  16. Muscle phosphorylase kinase deficiency

    DEFF Research Database (Denmark)

    Preisler, N; Orngreen, M C; Echaniz-Laguna, A

    2012-01-01

    To examine metabolism during exercise in 2 patients with muscle phosphorylase kinase (PHK) deficiency and to further define the phenotype of this rare glycogen storage disease (GSD).......To examine metabolism during exercise in 2 patients with muscle phosphorylase kinase (PHK) deficiency and to further define the phenotype of this rare glycogen storage disease (GSD)....

  17. Iron-Deficiency Anemia

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    Full Text Available ... loss and lead to iron-deficiency anemia. Common causes of blood loss that lead to iron-deficiency anemia include: Bleeding in your GI tract, from an ulcer, colon cancer, or regular use of medicines such as aspirin ...

  18. Iron-Deficiency Anemia

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    Full Text Available ... iron-deficiency anemia. Search the NIH Research Portfolio Online Reporting Tools (RePORT) to learn about research that ... iron-deficiency anemia in blood donors affects the quality of donated red blood cells, such as how ...

  19. Iron-Deficiency Anemia

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    Full Text Available ... blocks the intestine from taking up iron. Other medical conditions Other medical conditions that may lead to iron-deficiency anemia ... daily amount of iron. If you have other medical conditions that cause iron-deficiency anemia , such as ...

  20. Iron-Deficiency Anemia

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    Full Text Available ... anemia if you have certain risk factors , including pregnancy. To prevent iron-deficiency anemia, your doctor may recommend you eat heart-healthy foods or control other conditions that can cause iron-deficiency anemia. Blood tests to screen for ...

  1. Iron-Deficiency Anemia

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    Full Text Available ... Are you curious about how inflammation from chronic diseases can cause iron-deficiency anemia? Read more When there is ... DBDR) is a leader in research on the causes, prevention, and treatment of blood diseases, including iron-deficiency anemia. Search the NIH Research ...

  2. Nutritional iron deficiency

    NARCIS (Netherlands)

    Zimmermann, M.B.; Hurrell, R.F.

    2007-01-01

    Iron deficiency is one of the leading risk factors for disability and death worldwide, affecting an estimated 2 billion people. Nutritional iron deficiency arises when physiological requirements cannot be met by iron absorption from diet. Dietary iron bioavailability is low in populations consuming

  3. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Topics section only, or the News and Resources section. NHLBI Entire Site NHLBI Entire Site Health ... español Iron-deficiency anemia is a common type of anemia that occurs if you do not have enough iron in your body. People with mild or moderate iron-deficiency anemia ...

  4. Iron-Deficiency Anemia

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    Full Text Available ... for iron-deficiency anemia. Lifestyle habits Certain lifestyle habits may increase your risk for iron-deficiency anemia, including: Vegetarian or vegan eating patterns. Not eating enough iron-rich foods, such as meat and fish, may result in ...

  5. Iron-Deficiency Anemia

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    Full Text Available ... blood cells. Iron-deficiency anemia usually develops over time because your body’s intake of iron is too ... clamping of your newborn’s umbilical cord at the time of delivery. This may help prevent iron-deficiency ...

  6. Iron-Deficiency Anemia

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    Full Text Available ... other conditions that can cause iron-deficiency anemia. Blood tests to screen for iron-deficiency anemia To screen ... check the size of your liver and spleen. Blood tests Based on results from blood tests to screen ...

  7. Iron-Deficiency Anemia

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    Full Text Available ... also are hoping to determine which iron supplements work best to treat iron-deficiency anemia in children who do not consume the daily recommended amount of iron. Read less Participate in NHLBI Clinical Trials We lead or sponsor many studies related to iron-deficiency anemia. See if you ...

  8. Iron-Deficiency Anemia

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    Full Text Available ... en español Iron-deficiency anemia is a common type of anemia that occurs if you do not ... iron-deficiency anemia and help rule out other types of anemia. Treatment will explain treatment-related complications ...

  9. Iron deficiency in childhood

    NARCIS (Netherlands)

    Uijterschout, L.

    2015-01-01

    Iron deficiency (ID) is the most common micronutrient deficiency in the world. Iron is involved in oxygen transport, energy metabolism, immune response, and plays an important role in brain development. In infancy, ID is associated with adverse effects on cognitive, motor, and behavioral development

  10. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... anemia. Return to Signs, Symptoms, and Complications to review signs and symptoms as well as complications from iron-deficiency ... NIH]) Heavy Menstrual Bleeding (Centers for Disease Control and ... Dietary Supplement Fact Sheet (NIH) Iron-Deficiency Anemia (National Library ...

  11. Iron deficiency anemia

    Science.gov (United States)

    Anemia - iron deficiency ... iron from old red blood cells. Iron deficiency anemia develops when your body's iron stores run low. ... You may have no symptoms if the anemia is mild. Most of the time, ... slowly. Symptoms may include: Feeling weak or tired more often ...

  12. Iron-Deficiency Anemia

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    Full Text Available ... be at risk for iron-deficiency anemia. Lifestyle habits Certain lifestyle habits may increase your risk for iron-deficiency anemia, ... you are experiencing side effects such as a bad metallic taste, vomiting, diarrhea, constipation, or upset stomach. ...

  13. Iron-Deficiency Anemia

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    Full Text Available ... how we are using current research and advancing research to prevent iron-deficiency anemia. Participate in NHLBI Clinical Trials will explain our ongoing clinical studies that are investigating prevention strategies for iron-deficiency anemia. Signs, Symptoms, and Complications ...

  14. Muscle phosphoglycerate mutase deficiency revisited

    DEFF Research Database (Denmark)

    Naini, Ali; Toscano, Antonio; Musumeci, Olimpia

    2009-01-01

    storage disease type X and novel mutations in the gene encoding the muscle subunit of PGAM (PGAM2). DESIGN: Clinical, pathological, biochemical, and molecular analyses. SETTING: Tertiary care university hospitals and academic institutions. Patients A 37-year-old Danish man of Pakistani origin who had...... PGAM deficiency, and molecular studies revealed 2 novel homozygous mutations, a nonsense mutation and a single nucleotide deletion. Pathological studies of muscle showed mild glycogen accumulation but prominent tubular aggregates in both patients. CONCLUSIONS: We found that glycogen storage disease...

  15. Cobalamin deficiency, hyperhomocysteinemia, and dementia

    Directory of Open Access Journals (Sweden)

    Steven F Werder

    2010-04-01

    Full Text Available Steven F Werder1,21Kansas University School of Medicine – Wichita, Wichita, KS, USA; 2Community Health Center of Southeast Kansas, Pittsburg, KS, USAIntroduction: Although consensus guidelines recommend checking serum B12 in patients with dementia, clinicians are often faced with various questions: (1 Which patients should be tested? (2 What test should be ordered? (3 How are inferences made from such testing? (4 In addition to serum B12, should other tests be ordered? (5 Is B12 deficiency compatible with dementia of the Alzheimer’s type? (6 What is to be expected from treatment? (7 How is B12 deficiency treated?Methods: On January 31st, 2009, a Medline search was performed revealing 1,627 citations related to cobalamin deficiency, hyperhomocysteinemia, and dementia. After limiting the search terms, all abstracts and/or articles and other references were categorized into six major groups (general, biochemistry, manifestations, associations and risks, evaluation, and treatment and then reviewed in answering the above questions.Results: The six major groups above are described in detail. Seventy-five key studies, series, and clinical trials were identified. Evidence-based suggestions for patient management were developed.Discussion: Evidence is convincing that hyperhomocysteinemia, with or without hypovitaminosis B12, is a risk factor for dementia. In the absence of hyperhomocysteinemia, evidence is less convincing that hypovitaminosis B12 is a risk factor for dementia. B12 deficiency manifestations are variable and include abnormal psychiatric, neurological, gastrointestinal, and hematological findings. Radiological images of individuals with hyperhomocysteinemia frequently demonstrate leukoaraiosis. Assessing serum B12 and treatment of B12 deficiency is crucial for those cases in which pernicious anemia is suspected and may be useful for mild cognitive impairment and mild to moderate dementia. The serum B12 level is the standard initial test

  16. Vitamin B12 deficiency

    DEFF Research Database (Denmark)

    Green, Ralph; Allen, Lindsay H; Bjørke-Monsen, Anne-Lise

    2017-01-01

    , subclinical deficiency affects between 2.5% and 26% of the general population depending on the definition used, although the clinical relevance is unclear. B12 deficiency can affect individuals at all ages, but most particularly elderly individuals. Infants, children, adolescents and women of reproductive age...... remain debated. Management depends on B12 supplementation, either via high-dose oral routes or via parenteral administration. This Primer describes the current knowledge surrounding B12 deficiency, and highlights improvements in diagnostic methods as well as shifting concepts about the prevalence, causes...

  17. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... body to absorb iron from the gastrointestinal tract (GI tract). Blood loss When you lose blood, you ... to iron-deficiency anemia include: Bleeding in your GI tract, from an ulcer, colon cancer, or regular ...

  18. Iron-Deficiency Anemia

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    Full Text Available ... for gastrointestinal bleeding To see if gastrointestinal bleeding is causing your iron-deficiency anemia, your doctor may order the following procedures to guide treatment . Fecal ...

  19. Iron-Deficiency Anemia

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    Full Text Available ... complications, including heart failure and development delays in children. Explore this Health ... red blood cells. Iron-deficiency anemia usually develops over time because your body’s intake of iron ...

  20. Iron-Deficiency Anemia

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    Full Text Available ... Supplement Fact Sheet (NIH) Iron-Deficiency Anemia (National Library of Medicine, MedlinePlus) ... Privacy Policy Freedom of Information Act (FOIA) Accessibility Copyright and Usage No FEAR ...

  1. Iron-Deficiency Anemia

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    Full Text Available ... our clinical trials . Are you a frequent blood donor living in New York City? This study is looking at how iron-deficiency anemia in blood donors affects the quality of donated red blood cells, ...

  2. Vitamin D Deficiency

    Science.gov (United States)

    ... to other diseases. In children, it can cause rickets. Rickets is a rare disease that causes the bones ... and children are at higher risk of getting rickets. In adults, severe vitamin D deficiency leads to ...

  3. Iron-Deficiency Anemia

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    Full Text Available ... Health and Human Development, we are investigating how best to treat premature newborns with low hemoglobin levels. ... are hoping to determine which iron supplements work best to treat iron-deficiency anemia in children who ...

  4. Iron-Deficiency Anemia

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    Full Text Available ... and Strategic Vision Leadership Scientific Divisions Operations and Administration Advisory Committees Budget and Legislative Information Jobs and ... may recommend you eat heart-healthy foods or control other conditions that can cause iron-deficiency anemia. ...

  5. Iron-Deficiency Anemia

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    Full Text Available ... iron-deficiency anemia may cause the following complications: Depression Heart problems. If you do not have enough ... these usually go away within a day or two. Red blood cell transfusions. These may be used ...

  6. Iron-Deficiency Anemia

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    Full Text Available ... more. Read less Reminders Return to Causes to review how blood loss, not consuming the recommended amount ... iron-deficiency anemia. Return to Risk Factors to review family history, lifestyle, unhealthy environments, or other factors ...

  7. Iron-Deficiency Anemia

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    Full Text Available ... same for boys and girls. From birth to 6 months, babies need 0.27 mg of iron. ... for iron deficiency at certain ages: Infants between 6 and 12 months, especially if they are fed ...

  8. Iron-Deficiency Anemia

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    Full Text Available ... detect signs of iron-deficiency anemia and help rule out other types of anemia. Treatment will explain ... your blood. More testing may be needed to rule out other types of anemia. Tests for gastrointestinal ...

  9. Iron-Deficiency Anemia

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    Full Text Available ... red blood cells, called hemolysis . Hemolysis, in this case, is caused by strong muscle contractions and the ... to prevent iron-deficiency anemia. Participate in NHLBI Clinical Trials will explain our ongoing clinical studies that ...

  10. Iron-Deficiency Anemia

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    Full Text Available ... to improve health through research and scientific discovery. Improving health with current research Learn about the following ... deficiency anemia early in life affects later behavior, thinking, and mood during adolescence. Treating anemia in premature ...

  11. Iron-Deficiency Anemia

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    Full Text Available ... A-Z Clinical Trials Publications and Resources Health Education and Awareness ... If your doctor diagnoses you with iron-deficiency anemia, your treatment will depend on the cause and severity of the condition. Your ...

  12. Iron-Deficiency Anemia

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    Full Text Available ... your blood may be normal even if the total amount of iron in your body is low. ... iron-deficiency anemia in blood donors affects the quality of donated red blood cells, such as how ...

  13. Iron-Deficiency Anemia

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    Full Text Available ... interferes with the body’s ability to make hemoglobin. Family history and genetics Von Willebrand disease is an ... deficiency anemia. Return to Risk Factors to review family history, lifestyle, unhealthy environments, or other factors that ...

  14. Iron-Deficiency Anemia

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    Full Text Available ... diagnoses you with iron-deficiency anemia, your treatment will depend on the cause and severity of the ... of iron. The recommended daily amounts of iron will depend on your age, sex, and whether you ...

  15. Iron-Deficiency Anemia

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    Full Text Available ... from developing iron-deficiency anemia. Foods that are good sources of iron include dried beans, dried fruits, ... iron is needed, such as childhood and pregnancy. Good sources of iron are meat, poultry, fish, and ...

  16. Iron-Deficiency Anemia

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    Full Text Available ... A-Z Clinical Trials Publications and Resources Health Education and Awareness The Science Science Home Blood Disorders ... infancy has lasting effects. We are interested in learning how having iron-deficiency anemia early in life ...

  17. Iron-Deficiency Anemia

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    Full Text Available ... heart failure . Increased risk of infections Motor or cognitive development delays in children Pregnancy complications, such as ... iron-deficiency anemia may require intravenous (IV) iron therapy or a blood transfusion . Iron supplements Your doctor ...

  18. Iron-Deficiency Anemia

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    Full Text Available ... absorb iron and lead to iron-deficiency anemia. These conditions include: Intestinal and digestive conditions, such as ... tract. Inflammation from congestive heart failure or obesity . These chronic conditions can lead to inflammation that may ...

  19. Iron-Deficiency Anemia

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    Full Text Available ... Blood Disorders and Blood Safety Sleep Science and Sleep Disorders Lung Diseases Heart and Vascular Diseases Precision Medicine ... prevention and treatment of heart, lung, blood, and sleep disorders, including iron-deficiency anemia. Learn about the current ...

  20. Iron-Deficiency Anemia

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    Full Text Available ... iron-deficiency anemia early in life affects later behavior, thinking, and mood during adolescence. Treating anemia in ... Visit Children and Clinical Studies to hear experts, parents, and children talk about their experiences with clinical ...

  1. Factor V deficiency

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000550.htm Factor V deficiency To use the sharing features on ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  2. Factor II deficiency

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000549.htm Factor II deficiency To use the sharing features on ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  3. Factor X deficiency

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000553.htm Factor X deficiency To use the sharing features on ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  4. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... is caused by strong muscle contractions and the impact of feet repeatedly striking the ground, such as ... funding on iron-deficiency anemia. We stimulate high-impact research. Our Trans-Omics for Precision Medicine (TOPMed) ...

  5. Iron-Deficiency Anemia

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    Full Text Available ... may be diagnosed with iron-deficiency anemia if you have low iron or ferritin levels in your blood. More testing may be needed to rule out other types of anemia. Tests for gastrointestinal ...

  6. Iron-Deficiency Anemia

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    Full Text Available ... for your body to absorb iron from the gastrointestinal tract (GI tract). Blood loss When you lose blood, ... iron deficiency. Endurance athletes lose iron through their gastrointestinal tracts. They also lose iron through the breakdown of ...

  7. Iron-Deficiency Anemia

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    Full Text Available ... vegetables. Foods rich in vitamin C, such as oranges, strawberries, and tomatoes, may help increase your absorption ... deficiency anemia, your doctor may recommend erythropoiesis stimulating agents (esa) . These medicines stimulate the bone marrow to ...

  8. Iron-Deficiency Anemia

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    Full Text Available ... were born prematurely may be at an even higher risk, as most of a newborn’s iron stores ... men of the same age. Women are at higher risk for iron-deficiency anemia under some circumstances, ...

  9. Iron-Deficiency Anemia

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    Full Text Available ... Iron-Deficiency Anemia (National Library of Medicine, MedlinePlus) Building 31 31 Center Drive Bethesda, MD 20892 Learn ... and Usage No FEAR Act Grants and Funding Building 31 31 Center Drive Bethesda, MD 20892 Learn ...

  10. Iron-Deficiency Anemia

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    Full Text Available ... may recommend erythropoiesis stimulating agents (esa) . These medicines stimulate the bone marrow to make more red blood ... NHLBI is funding on iron-deficiency anemia. We stimulate high-impact research. Our Trans-Omics for Precision ...

  11. Iron-Deficiency Anemia

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    Full Text Available ... tests, especially in infants and small children Heavy menstrual periods Injury or surgery Urinary tract bleeding Consuming ... iron-deficiency anemia from trauma, surgery, or heavy menstrual periods. Individuals with a gene for hemophilia, including ...

  12. Iron-Deficiency Anemia

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    Full Text Available ... and naproxen Certain rare genetic conditions such as hereditary hemorrhagic telangiectasia, which causes bleeding in the bowels ... iron-deficiency anemia may cause the following complications: Depression Heart problems. If you do not have enough ...

  13. Iron-Deficiency Anemia

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    Full Text Available ... lead in their blood from their environment or water. Lead interferes with the body’s ability to make ... iron-deficiency anemia in blood donors affects the quality of donated red blood cells, such as how ...

  14. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... also often take other medicines—such as proton pump inhibitors, anticoagulants, or blood thinners—that may cause iron-deficiency anemia. Proton pump inhibitors interfere with iron absorption, and blood thinners ...

  15. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Cells From Iron-deficient Donors: Recovery and Storage Quality. Learn more about participating in a clinical trial . View all trials from ClinicalTrials.gov . Visit Children and Clinical Studies to hear experts, parents, and ...

  16. Iron-Deficiency Anemia

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    Full Text Available ... Look for Treatment will discuss medicines and eating pattern changes that your doctors may recommend if you ... iron-deficiency anemia, including: Vegetarian or vegan eating patterns. Not eating enough iron-rich foods, such as ...

  17. Iron-Deficiency Anemia

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    Full Text Available ... girls. From birth to 6 months, babies need 0.27 mg of iron. This number goes up ... screen blood donors for low iron stores. Reliable point-of-care testing may help identify iron deficiency ...

  18. Iron-Deficiency Anemia

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    Full Text Available ... striking the ground, such as with marathon runners. Sex Girls and women between the ages of 14 ... developing iron-deficiency anemia. Foods that are good sources of iron include dried beans, dried fruits, eggs, ...

  19. Iron-Deficiency Anemia

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    Full Text Available ... increase your risk for iron-deficiency anemia, including: Vegetarian or vegan eating patterns. Not eating enough iron- ... factors , such as if you are following a vegetarian eating pattern, your doctor may recommend changes to ...

  20. Iron-Deficiency Anemia

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    Full Text Available ... deficiency anemia. Proton pump inhibitors interfere with iron absorption, and blood thinners increase the likelihood of bleeding ... oranges, strawberries, and tomatoes, may help increase your absorption of iron. If you are pregnant, talk to ...

  1. Iron-Deficiency Anemia

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    Full Text Available ... screen for iron-deficiency anemia, your doctor may order a blood test called a complete blood count ( ... your risk factors , do a physical exam, or order blood tests or other diagnostic tests. Physical exam ...

  2. Iron-Deficiency Anemia

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    Full Text Available ... duodenum, the first part of the small intestine just beyond the stomach. Even if you have enough ... clamping of your newborn’s umbilical cord at the time of delivery. This may help prevent iron-deficiency ...

  3. Iron-Deficiency Anemia

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    Full Text Available ... less than 12 g/dl for women is diagnostic of anemia. In iron-deficiency anemia, red blood ... both full-term and preterm infants. Look for Diagnosis will explain tests and procedures that your doctor ...

  4. Iron-Deficiency Anemia

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    Full Text Available ... less than 12 g/dl for women is diagnostic of anemia. In iron-deficiency anemia, red blood ... physical exam, or order blood tests or other diagnostic tests. Physical exam Your doctor may ask about ...

  5. Iron-Deficiency Anemia

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    Full Text Available ... risk for iron-deficiency anemia, including: Vegetarian or vegan eating patterns. Not eating enough iron-rich foods, ... iron-fortified foods that have iron added. Vegetarian diets can provide enough iron if you choose nonmeat ...

  6. Iron-Deficiency Anemia

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    Full Text Available ... bleeding. If undiagnosed or untreated, iron-deficiency anemia can cause serious complications, including heart failure and development ... iron is too low. Low intake of iron can happen because of blood loss, consuming less than ...

  7. Iron-Deficiency Anemia

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    Full Text Available ... improved health for people with iron-deficiency anemia. Recipient Epidemiology Donor Studies program findings help to protect blood donors . NHLBI’s Recipient Epidemiology Donor Studies (REDS) program , which began in ...

  8. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... a frequent blood donor living in New York City? This study is looking at how iron-deficiency ... frequently. This study is located in New York City, and is recruiting by invitation only. View more ...

  9. Iron-Deficiency Anemia

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    Full Text Available ... to 11 mg for children ages 7 to 12 months, and down to 7 mg for children ... deficiency at certain ages: Infants between 6 and 12 months, especially if they are fed only breast ...

  10. Iron-Deficiency Anemia

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    Full Text Available ... in our clinical trials . Are you a frequent blood donor living in New York City? This study is looking at how iron-deficiency anemia in blood donors affects the quality of donated red blood cells, ...

  11. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron-deficiency anemia may cause the following complications: Depression Heart problems. If you do not have enough ... prevent complications such as abnormal heart rhythms and depression. Learn the warning signs of serious complications and ...

  12. Iron-Deficiency Anemia

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    Full Text Available ... prevent complications such as abnormal heart rhythms and depression. Learn the warning signs of serious complications and ... donors for low iron stores. Reliable point-of-care testing may help identify iron deficiency before potentially ...

  13. Iron-Deficiency Anemia

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    Full Text Available ... be at risk for iron-deficiency anemia. Lifestyle habits Certain lifestyle habits may increase your risk for ... Surgery, upper endoscopy or colonoscopy, to stop bleeding. Healthy lifestyle changes To help you meet your daily ...

  14. Iron-Deficiency Anemia

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    Full Text Available ... breastfeeding women older than 18 need 9 mg. Problems absorbing iron Even if you consume the recommended ... interested in learning how having iron-deficiency anemia early in life affects later behavior, thinking, and mood ...

  15. Iron-Deficiency Anemia

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    Full Text Available ... starch. Restless legs syndrome Shortness of breath Weakness Complications Undiagnosed or untreated iron-deficiency anemia may cause ... as complete blood count and iron studies. Prevent complications over your lifetime To prevent complications from iron- ...

  16. Iron-Deficiency Anemia

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    Full Text Available ... you do not have enough iron in your body. People with mild or moderate iron-deficiency anemia ... and where to find more information. Causes Your body needs iron to make healthy red blood cells. ...

  17. Iron-Deficiency Anemia

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    Full Text Available ... iron-deficiency anemia. Learn about the current and future NHLBI efforts to improve health through research and ... blood donors. Cardiovascular Health Study identifies predictors of future health problems in older adults. The NHLBI-sponsored ...

  18. Iron-Deficiency Anemia

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    Full Text Available ... as most of a newborn’s iron stores are developed during the third trimester of pregnancy. Children between ... This makes it harder to stop bleeding and can increase the risk of iron-deficiency anemia from ...

  19. Iron-Deficiency Anemia

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    Full Text Available ... an MCV of less than 80 femtoliters (fL). Prevention strategies If you have certain risk factors , such ... explain our ongoing clinical studies that are investigating prevention strategies for iron-deficiency anemia. Signs, Symptoms, and ...

  20. Iron-Deficiency Anemia

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    Full Text Available ... Safety Sleep Science and Sleep Disorders Lung Diseases Heart and Vascular Diseases Precision Medicine Activities Obesity, Nutrition, ... iron-deficiency anemia can cause serious complications, including heart failure and development delays in children. Explore this ...

  1. Iron-Deficiency Anemia

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    Full Text Available ... symptoms. More severe iron-deficiency anemia may cause fatigue or tiredness, shortness of breath, or chest pain. ... in the hands and feet Difficulty concentrating Dizziness Fatigue, or feeling tired, is the most common symptom. ...

  2. Manganese deficiency in plants

    DEFF Research Database (Denmark)

    Schmidt, Sidsel Birkelund; Jensen, Poul Erik; Husted, Søren

    2016-01-01

    Manganese (Mn) is an essential plant micronutrient with an indispensable function as a catalyst in the oxygen-evolving complex (OEC) of photosystem II (PSII). Even so, Mn deficiency frequently occurs without visual leaf symptoms, thereby masking the distribution and dimension of the problem...... restricting crop productivity in many places of the world. Hence, timely alleviation of latent Mn deficiency is a challenge in promoting plant growth and quality. We describe here the key mechanisms of Mn deficiency in plants by focusing on the impact of Mn on PSII stability and functionality. We also address...... the mechanisms underlying the differential tolerance towards Mn deficiency observed among plant genotypes, which enable Mn-efficient plants to grow on marginal land with poor Mn availability....

  3. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... to learn more about iron-deficiency anemia, our role in research and clinical trials to improve health, ... of Blood Diseases and Resources (DBDR) is a leader in research on the causes, prevention, and treatment ...

  4. Iron-Deficiency Anemia

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    Full Text Available ... Treatment will explain treatment-related complications or side effects. Diagnosis Iron-deficiency anemia may be detected during ... to your doctor if you are experiencing side effects such as a bad metallic taste, vomiting, diarrhea, ...

  5. Iron-Deficiency Anemia

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    Full Text Available ... an increased risk for iron-deficiency anemia because of your age, unhealthy environments, family ... 12 months, especially if they are fed only breast milk or are fed formula that is not fortified ...

  6. Iron-Deficiency Anemia

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    Full Text Available ... blood tests, especially in infants and small children Heavy menstrual periods Injury or surgery Urinary tract bleeding ... of iron-deficiency anemia from trauma, surgery, or heavy menstrual periods. Individuals with a gene for hemophilia, ...

  7. Iron-Deficiency Anemia

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    Full Text Available ... developing iron-deficiency anemia. Foods that are good sources of iron include dried beans, dried fruits, eggs, ... is needed, such as childhood and pregnancy. Good sources of iron are meat, poultry, fish, and iron- ...

  8. Iron-Deficiency Anemia

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    Full Text Available ... Individuals with a gene for hemophilia, including symptomatic female carriers who have heavy menstrual periods, may be ... anemia. Endurance activities and athletes. Athletes, especially young females, are at risk for iron deficiency. Endurance athletes ...

  9. Iron-Deficiency Anemia

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    Full Text Available ... and Strategic Vision Leadership Scientific Divisions Operations and Administration Advisory Committees Budget and Legislative Information Jobs and ... blood cells. Iron-deficiency anemia usually develops over time because your body’s intake of iron is too ...

  10. Iron-Deficiency Anemia

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    Full Text Available ... MCV of less than 80 femtoliters (fL). Prevention strategies If you have certain risk factors , such as ... our ongoing clinical studies that are investigating prevention strategies for iron-deficiency anemia. Signs, Symptoms, and Complications ...

  11. Iron-Deficiency Anemia

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    Full Text Available ... may recommend you eat heart-healthy foods or control other conditions that can cause iron-deficiency anemia. ... heavy menstrual bleeding, your doctor will want to control these other conditions to prevent you from developing ...

  12. Iron-Deficiency Anemia

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    Full Text Available ... lead to iron-deficiency anemia include: End-stage kidney failure, where there is blood loss during dialysis. People who have chronic kidney disease also often take other medicines—such as ...

  13. Iron-Deficiency Anemia

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    Full Text Available ... may be at risk for iron-deficiency anemia. Lifestyle habits Certain lifestyle habits may increase your risk ... upper endoscopy or colonoscopy, to stop bleeding. Healthy lifestyle changes To help you meet your daily recommended ...

  14. Iron-Deficiency Anemia

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    Full Text Available ... endoscopy or colonoscopy, to stop bleeding. Healthy lifestyle changes To help you meet your daily recommended iron ... iron-deficiency anemia early in life affects later behavior, thinking, and mood during adolescence. Treating anemia in ...

  15. Iron-Deficiency Anemia

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    Full Text Available ... Chest pain Coldness in the hands and feet Difficulty concentrating Dizziness Fatigue, or feeling tired, is the ... Our support of SBIR/STTR programs is helping advance research in iron-deficiency anemia, in part by ...

  16. Iron-Deficiency Anemia

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    Full Text Available ... infancy has lasting effects. We are interested in learning how having iron-deficiency anemia early in life ... Customer Service/Center for Health Information Email Alerts Jobs and Careers Site Index About NHLBI National Institute ...

  17. Iron-Deficiency Anemia

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    Full Text Available ... family history and genetics , lifestyle habits, or sex. Age You may be at increased risk for iron ... Signs, Symptoms, and Complications Iron-deficiency anemia can range from mild to severe. People with mild or ...

  18. Iron-Deficiency Anemia

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    Full Text Available ... iron to prepare for blood loss during delivery. Screening and Prevention Your doctor may screen you for ... and symptoms of iron-deficiency anemia. Return to Screening and Prevention to review tests to screen for ...

  19. [Iron deficiency and pica].

    Science.gov (United States)

    Muñoz, J A; Marcos, J; Risueño, C E; de Cos, C; López, R; Capote, F J; Martín, M V; Gil, J L

    1998-02-01

    To study the relationship between pica and iron-lack anaemia in a series of iron-deficiency patients in order to establish the pathogenesis of such relationship. Four-hundred and thirty-three patients were analysed. Pica was studied by introducing certain diet queries into the clinical history. All patients received oral iron and were periodically controlled with the usual clinico-haematological procedures. Pica was present in 23 patients (5.3%). Eight nourishing (namely, coffee grains, almonds, chocolate, ice, lettuce, carrots, sunflower seeds and bread) and 2 non-nourishing (clay and paper) substances were involved. A second episode of pica appeared in 9 cases upon relapsing of iron deficiency. Both anaemia and pica were cured by etiologic and substitutive therapy in all instances. No clear correlation was found with either socio-economic status or pathogenetic causes of iron deficiency and pica, and no haematological differences were seen between patients with pica and those without this alteration. (1) The pathogenesis of pica is unclear, although it appears unrelated to the degree of iron deficiency. (2) According to the findings in this series, pica seems a consequence of iron deficiency rather than its cause. (3) Adequate therapy can cure both conditions, although pica may reappear upon relapse of iron deficiency.

  20. Myoadenylate deaminase deficiency, hypertrophic cardiomyopathy and gigantism syndrome.

    Science.gov (United States)

    Skyllouriotis, M L; Marx, M; Bittner, R E; Skyllouriotis, P; Gross, M; Wimmer, M

    1997-07-01

    We report a 20-year-old man with gigantism syndrome, hypertrophic cardiomyopathy, muscle weakness, exercise intolerance, and severe psychomotor retardation since childhood. Histochemical and biochemical analysis of skeletal muscle biopsy revealed myoadenylate deaminase deficiency; molecular genetic analysis confirmed the diagnosis of primary (inherited) myoadenylate deaminase deficiency. Plasma, urine, and muscle carnitine concentrations were reduced. L-Carnitine treatment led to gradual improvement in exercise tolerance and cognitive performance; plasma and tissue carnitine levels returned to normal, and echocardiographic evidence of left ventricular hypertrophy disappeared. The combination of inherited myoadenylate deaminase deficiency, gigantism syndrome and carnitine deficiency has not previously been described.

  1. Vitamin Excess and Deficiency.

    Science.gov (United States)

    Diab, Liliane; Krebs, Nancy F

    2018-04-01

    The published literature supports the high prevalence of supplement use in children and adolescents in the United States. Pediatricians today are faced with questions from parents and patients about the benefits, safety, efficacy, and correct dose of vitamins and minerals. In this article, we review 7 vitamins with the most clinical relevance as judged by abundance in food, risks and symptoms of deficiency, and potential for toxicity. Specifically, we focus on possible clinical scenarios that can be indicative of nutritional deficiency. We synthesize and summarize guidelines from nutrition experts, various medical societies, the World Health Organization, and the American Academy of Pediatrics. © American Academy of Pediatrics, 2018. All rights reserved.

  2. Vitamin D deficiency and stroke

    Directory of Open Access Journals (Sweden)

    2012-12-01

    Full Text Available Vitamin D comprises a group of fat-soluble pro-hormones, obtained from sun exposure, food, and supplements, and it must undergo two hydroxylation reactions to be activated in the body. Several studies have shown the role of vitamin D in mineral metabolism regulation, especially calcium, phosphorus, and bone metabolism. Some factors such as inadequate vitamin intake and liver or kidney disorders can lead to vitamin D deficiency. Furthermore, vitamin D malnutrition may also be linked to susceptibility to chronic diseases such as heart failure, peripheral artery disease, high blood pressure, cognitive impairment including foggy brain and memory loss, and autoimmune diseases including diabetes type I. Recent research has revealed that low levels of vitamin D increase the risk of cardiovascular-related morbidity (Sato et al., 2004 and mortality (Pilz et al., 2008. Also, hypertension contributes to a reduction in bone mineral density and increase in the incidence of stroke and death. This article reviews the function and physiology of vitamin D and examines the effects of vitamin D deficiency on susceptibility to stroke, as a cardiovascular event, and its morbidity and subsequent mortality.

  3. What Is Combined Deficiency of Vitamin K-Dependent Clotting Factors?

    Science.gov (United States)

    ... Deficiency Factor V Deficiency Combined FV & FVIII Deficiencies Factor VII Deficiency Factor X Deficiency Factor XI Deficiency Factor ... Deficiency Factor V Deficiency Combined FV & FVIII Deficiencies Factor VII Deficiency Factor X Deficiency Factor XI Deficiency Factor ...

  4. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... grams per deciliter (g/dl) for men and less than 12 g/dl for women is diagnostic of anemia. In iron-deficiency anemia, ... blood levels of iron will be low, or less than 10 micromoles per liter (mmol/L) for both men and women. Normal levels are 10 to 30 mmol/L. ...

  5. Alpha1-antitrypsin deficiency

    DEFF Research Database (Denmark)

    Stolk, Jan; Seersholm, Niels; Kalsheker, Noor

    2006-01-01

    The Alpha One International Registry (AIR), a multinational research program focused on alpha1-antitrypsin (AAT) deficiency, was formed in response to a World Health Organization recommendation. Each of the nearly 20 participating countries maintains a national registry of patients with AAT defic...

  6. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... is blood loss during dialysis. People who have chronic kidney disease also often take other medicines—such as proton ... reduces iron absorption. Other treatments If you have chronic kidney disease and iron-deficiency anemia, your doctor may recommend ...

  7. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... A-Z Clinical Trials Publications and Resources Health Education and Awareness The Science Science Home Blood Disorders ... Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) ... We are interested in learning how having iron-deficiency anemia early in life ...

  8. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Science Science Home Blood Disorders and Blood Safety Sleep Science and Sleep Disorders Lung Diseases Heart and Vascular Diseases Precision ... prevention and treatment of heart, lung, blood, and sleep disorders, including iron-deficiency anemia. Learn about the ...

  9. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... infection. A history of gastrointestinal surgery, such as weight-loss surgery—especially gastric bypass—or gastrectomy. Certain rare ... prevention and treatment of heart, lung, blood, and sleep disorders, including iron-deficiency anemia. Learn about the ...

  10. Vitamin B12 deficiency

    Science.gov (United States)

    Vitamin B12 (B12; also known as cobalamin) is a B vitamin that has an important role in cellular metabolism, especially in DNA synthesis, methylation and mitochondrial metabolism. Clinical B12 deficiency with classic haematological and neurological manifestations is relatively uncommon. However, sub...

  11. Leukocyte adhesion deficiencies

    NARCIS (Netherlands)

    van de Vijver, Edith; van den Berg, Timo K.; Kuijpers, Taco W.

    2013-01-01

    During inflammation, leukocytes play a key role in maintaining tissue homeostasis through elimination of pathogens and removal of damaged tissue. Leukocytes migrate to the site of inflammation by crawling over and through the blood vessel wall, into the tissue. Leukocyte adhesion deficiencies (ie,

  12. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron supplements work best to treat iron-deficiency anemia in children who do not consume the daily recommended amount ... and Clinical Studies to hear experts, parents, and children talk about their experiences with clinical ... Anemia Arrhythmia Blood Donation Blood Tests Blood ...

  13. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Working at the NHLBI Contact and FAQs Accessible Search Form Search the NHLBI, use the drop down list to ... treatment of blood diseases, including iron-deficiency anemia. Search the NIH Research Portfolio Online Reporting Tools (RePORT) ...

  14. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... or even heart failure . Increased risk of infections Motor or cognitive development delays in children Pregnancy complications, ... Upper endoscopy to look for bleeding in the esophagus, stomach, and the first part of the ... blood, and sleep disorders, including iron-deficiency anemia. Learn about the current ...

  15. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... how having iron-deficiency anemia early in life affects later behavior, thinking, and mood during adolescence. Treating anemia in premature or very small newborns . In collaboration with the Eunice Kennedy Shriver National Institute of Child Health and Human Development, we are investigating how ...

  16. Iron deficiency in children

    African Journals Online (AJOL)

    cell and excess iron is stored as ferritin to protect the cell from oxidative ... iron deficiency has negative effects during pregnancy and in the postpartum period, which affects maternal health ... use of undiluted cow's milk and a predominant cow's milk intake in .... on bone marrow smear or biopsy for the definitive diagnosis of.

  17. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Certain conditions or medicines can decrease your body’s ability to absorb iron and lead to iron-deficiency ... environment or water. Lead interferes with the body’s ability to make hemoglobin. Family history and genetics Von ...

  18. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... supplements. Iron supplements can change how certain medicines work. Your doctor may suggest check-ups to make sure your ... To prevent complications from iron-deficiency anemia, your doctor may ... during certain stages of life when more iron is needed, such as childhood ...

  19. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... an MCV of less than 80 femtoliters (fL). Prevention strategies If you have certain risk factors , such as if you are following a ... unhealthy environments, or other factors that increase your risk of developing iron-deficiency ... to Screening and Prevention to review tests to screen for and strategies ...

  20. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Services’ National Institutes of Health (NIH)—the Nation’s biomedical research agency that makes important scientific discoveries to improve ... efforts for iron-deficiency anemia. Learn about exciting research areas that ... This could help develop new therapies for conditions that affect the balance of iron ...

  1. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Complications Undiagnosed or untreated iron-deficiency anemia may cause the following complications: Depression Heart problems. If you do not have enough hemoglobin-carrying red blood cells, your heart has to work harder to move oxygen-rich blood through your ...

  2. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... the Eunice Kennedy Shriver National Institute of Child Health and Human Development, we are investigating how best to treat premature newborns with low hemoglobin levels. We also are hoping to determine which iron supplements work best to treat iron-deficiency anemia in children ...

  3. MCAD deficiency in Denmark

    DEFF Research Database (Denmark)

    Andresen, Brage Storstein; Lund, Allan Meldgaard; Hougaard, David Michael

    2012-01-01

    Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is the most common defect of fatty acid oxidation. Many countries have introduced newborn screening for MCADD, because characteristic acylcarnitines can easily be identified in filter paper blood spot samples by tandem mass spectrometry (MS/M...

  4. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... NHLBI News NHLBI in the Press Research Features All Events Past Events Upcoming Events About NHLBI About NHLBI Home Mission and Strategic Vision ... deficient Donors: Recovery and Storage Quality. Learn more about ... trial . View all trials from ClinicalTrials.gov . Visit Children and Clinical ...

  5. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... A-Z Clinical Trials Publications and Resources Health Education and Awareness The Science Science Home Blood Disorders ... Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) programs. Our ... more information about Donor Iron Deficiency Study - Red Blood Cells ...

  6. Isolated sulfite oxidase deficiency.

    Science.gov (United States)

    Rupar, C A; Gillett, J; Gordon, B A; Ramsay, D A; Johnson, J L; Garrett, R M; Rajagopalan, K V; Jung, J H; Bacheyie, G S; Sellers, A R

    1996-12-01

    Isolated sulfite oxidase (SO) deficiency is an autosomal recessively inherited inborn error of sulfur metabolism. In this report of a ninth patient the clinical history, laboratory results, neuropathological findings and a mutation in the sulfite oxidase gene are described. The data from this patient and previously published patients with isolated sulfite oxidase deficiency and molybdenum cofactor deficiency are summarized to characterize this rare disorder. The patient presented neonatally with intractable seizures and did not progress developmentally beyond the neonatal stage. Dislocated lenses were apparent at 2 months. There was increased urine excretion of sulfite and S-sulfocysteine and a decreased concentration of plasma cystine. A lactic acidemia was present for 6 months. Liver sulfite oxidase activity was not detectable but xanthine dehydrogenase activity was normal. The boy died of respiratory failure at 32 months. Neuropathological findings of cortical necrosis and extensive cavitating leukoencephalopathy were reminiscent of those seen in severe perinatal asphyxia suggesting an etiology of energy deficiency. A point mutation that resulted in a truncated protein missing the molybdenum-binding site has been identified.

  7. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... do not have enough iron in your body. People with mild or moderate iron-deficiency anemia may ... as a TMRPSS6 gene mutation that causes a person’s body to make too much of a hormone ...

  8. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... anemia, including: Vegetarian or vegan eating patterns. Not eating enough iron-rich foods, such as meat and fish, may result in ... deficiency anemia, your doctor may recommend heart-healthy eating and choosing iron-rich foods, especially during certain stages of life when more ...

  9. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron-deficiency anemia early in life affects later behavior, thinking, and mood during adolescence. Treating anemia in premature or very small newborns . In collaboration with the Eunice Kennedy Shriver National Institute of Child Health and Human Development, we are investigating how best to treat ...

  10. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron-deficiency anemia, including: Vegetarian or vegan eating patterns. Not eating enough iron-rich foods, such as meat and fish, may result in you getting less than the recommended daily amount of iron. Frequent blood donation. Individuals who donate blood often may be ...

  11. Familial lipoprotein lipase deficiency

    Science.gov (United States)

    ... lack an enzyme called lipoprotein lipase. Without this enzyme, the body cannot break down fat from digested food. Fat particles called chylomicrons build up in the blood. Risk factors include a family history of lipoprotein lipase deficiency. The condition is usually ...

  12. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Activities Obesity, Nutrition, and Physical Activity Population and Epidemiology Studies Women’s Health All Science A-Z Grants ... health for people with iron-deficiency anemia. Recipient Epidemiology Donor Studies program findings help to protect blood ...

  13. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... and save lives. We are committed to advancing science and translating discoveries into clinical practice to promote the prevention and treatment of heart, lung, blood, and sleep disorders, including iron-deficiency anemia. Learn about the current and future NHLBI efforts to improve health through ...

  14. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... iron-deficiency anemia early in life affects later behavior, thinking, and mood during adolescence. Treating anemia in premature or very small newborns . In collaboration with the Eunice Kennedy Shriver National Institute of Child Health and Human Development, we are investigating how ...

  15. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... with the Eunice Kennedy Shriver National Institute of Child Health and Human Development, we are investigating how best to treat premature newborns with low hemoglobin levels. We also are hoping to determine which iron supplements work best to treat iron-deficiency anemia in children ...

  16. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... of the body. When your heart has to work harder, this can lead to several conditions: irregular heartbeats called arrhythmias , a heart murmur , an ... chronic conditions, iron-deficiency anemia can make their condition worse or result in treatments not working as well. Look for Diagnosis will discuss any ...

  17. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... normally stores but has used up. Increase your intake of vitamin C to help your body absorb iron. Avoid drinking black tea, which reduces iron absorption. Other treatments If you have chronic kidney disease and iron-deficiency anemia, your doctor may recommend ...

  18. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... deficiency anemia. We stimulate high-impact research. Our Trans-Omics for Precision Medicine (TOPMed) Program now includes ... Studies (REDS) program Blood Disorders and Blood Safety Trans-Omics for Precision Medicine (TOPMed) Program Non-NHLBI ...

  19. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Medicine (TOPMed) Program Non-NHLBI resources Anemia (National Library of Medicine, MedlinePlus) Anemia in Chronic Kidney Disease ( ... Supplement Fact Sheet (NIH) Iron-Deficiency Anemia (National Library of Medicine, MedlinePlus) Building 31 31 Center Drive ...

  20. Iodine-deficiency disorders

    NARCIS (Netherlands)

    Zimmermann, M.B.; Jooste, P.L.; Pandav, C.S.

    2008-01-01

    billion individuals worldwide have insufficient iodine intake, with those in south Asia and sub-Saharan Africa particularly affected. Iodine deficiency has many adverse effects on growth and development. These effects are due to inadequate production of thyroid hormone and are termed

  1. Urinary AASA excretion is elevated in patients with molybdenum cofactor deficiency and isolated sulphite oxidase deficiency

    NARCIS (Netherlands)

    Mills, P.B.; Footitt, E.J.; Ceyhan, S.; Waters, P.J.; Jakobs, C.A.J.M.; Clayton, P.T.; Struijs, E.A.

    2012-01-01

    Analysis of α-aminoadipic semialdehyde is an important tool in the diagnosis of antiquitin deficiency (pyridoxine-dependent epilepsy). However continuing use of this test has revealed that elevated urinary excretion of α-aminoadipic semialdehyde is not only found in patients with

  2. Physiological roles revealed by ghrelin and ghrelin receptor deficient mice

    Science.gov (United States)

    Ghrelin is a hormone made in the stomach and known primarily for its growth hormone releasing and orexigenic properties. Nevertheless, ghrelin through its receptor, the GHS-R1a, has been shown to exert many roles including regulation of glucose homeostasis, memory & learning, food addiction and neur...

  3. Iron deficiency and cognitive functions

    Directory of Open Access Journals (Sweden)

    Jáuregui-Lobera I

    2014-11-01

    Full Text Available Ignacio Jáuregui-Lobera Department of Nutrition and Bromatology, Pablo de Olavide University, Seville, Spain Abstract: Micronutrient deficiencies, especially those related to iodine and iron, are linked to different cognitive impairments, as well as to potential long-term behavioral changes. Among the cognitive impairments caused by iron deficiency, those referring to attention span, intelligence, and sensory perception functions are mainly cited, as well as those associated with emotions and behavior, often directly related to the presence of iron deficiency anemia. In addition, iron deficiency without anemia may cause cognitive disturbances. At present, the prevalence of iron deficiency and iron deficiency anemia is 2%–6% among European children. Given the importance of iron deficiency relative to proper cognitive development and the alterations that can persist through adulthood as a result of this deficiency, the objective of this study was to review the current state of knowledge about this health problem. The relevance of iron deficiency and iron deficiency anemia, the distinction between the cognitive consequences of iron deficiency and those affecting specifically cognitive development, and the debate about the utility of iron supplements are the most relevant and controversial topics. Despite there being methodological differences among studies, there is some evidence that iron supplementation improves cognitive functions. Nevertheless, this must be confirmed by means of adequate follow-up studies among different groups. Keywords: iron deficiency, anemia, cognitive functions, supplementation

  4. Lipoprotein lipase deficiency with visceral xanthomas

    Energy Technology Data Exchange (ETDEWEB)

    Servaes, Sabah; Bellah, Richard [Department of Radiology, Philadelphia, PA (United States); Verma, Ritu [Department of Gastroenterology, Philadelphia, PA (United States); Pawel, Bruce [Department of Pathology, Philadelphia, PA (United States)

    2010-08-15

    Lipoprotein lipase deficiency (LLD) is a rare metabolic disorder that typically presents with skin xanthomas and pancreatitis in childhood. We report a case of LLD in an infant who presented with jaundice caused by a pancreatic head mass. Abdominal imaging also incidentally revealed hyperechoic renal masses caused by renal xanthomas. This appearance of the multiple abdominal masses makes this a unique infantile presentation of LLD. (orig.)

  5. Adult growth hormone deficiency

    Directory of Open Access Journals (Sweden)

    Vishal Gupta

    2011-01-01

    Full Text Available Adult growth hormone deficiency (AGHD is being recognized increasingly and has been thought to be associated with premature mortality. Pituitary tumors are the commonest cause for AGHD. Growth hormone deficiency (GHD has been associated with neuropsychiatric-cognitive, cardiovascular, neuromuscular, metabolic, and skeletal abnormalities. Most of these can be reversed with growth hormone therapy. The insulin tolerance test still remains the gold standard dynamic test to diagnose AGHD. Growth hormone is administered subcutaneously once a day, titrated to clinical symptoms, signs and IGF-1 (insulin like growth factor-1. It is generally well tolerated at the low-doses used in adults. Pegylated human growth hormone therapy is on the horizon, with a convenient once a week dosing.

  6. Epidemiology of SHOX deficiency.

    Science.gov (United States)

    Nicolosi, A; Caruso-Nicoletti, M

    2010-06-01

    Deletion of short stature homeobox-containing (SHOX) gene, in the pseudoautosomal region (PAR1) of X and Y chromosomes, is an important cause of short stature. Homozygous loss of SHOX results in the more severe Langer mesomelic dysplasia, while SHOX haploinsufficiency cause a wide spectrum of short stature phenotypes, including patients with Turner syndrome, Leri Weill dyschondrosteosis (LWD), and idiopathic short stature (ISS). In Turner syndrome, haploinsufficiency of SHOX gene, as well as short stature, are present in 100%; nevertheless, SHOX deficiency accounts for only two-thirds of Turner patients' short stature. In LWD the prevalence of SHOX gene anomalies varies from 56% to 100%. This wide range might be due to different factors such as selection criteria of patients, sample size, and method used for screening SHOX mutations. The real challenge is to establish the prevalence of SHOX deficiency in ISS children given that published studies have reported this association with a very broad frequency range varying from 1.5% to 15%. An important variable in these studies is represented by the method used for screening SHOX mutations and sometimes by differences in patient selection. Short stature is present by definition in 3 out of 100 subjects; if we consider a frequency of SHOX defects of 3% among ISS, we should expect a population prevalence of 1 in 1000. This prevalence would be higher than that of GH deficiency (1:3,500) and of Turner syndrome (1:2,500 females), suggesting that SHOX deficiency could be one of the most frequent monogenetic causes of short stature.

  7. Biotin and biotinidase deficiency

    OpenAIRE

    Zempleni, Janos; Hassan, Yousef I; Wijeratne, Subhashinee SK

    2008-01-01

    Biotin is a water-soluble vitamin that serves as an essential coenzyme for five carboxylases in mammals. Biotin-dependent carboxylases catalyze the fixation of bicarbonate in organic acids and play crucial roles in the metabolism of fatty acids, amino acids and glucose. Carboxylase activities decrease substantially in response to biotin deficiency. Biotin is also covalently attached to histones; biotinylated histones are enriched in repeat regions in the human genome and appear to play a role...

  8. L-arginine:glycine amidinotransferase deficiency protects from metabolic syndrome.

    Science.gov (United States)

    Choe, Chi-un; Nabuurs, Christine; Stockebrand, Malte C; Neu, Axel; Nunes, Patricia; Morellini, Fabio; Sauter, Kathrin; Schillemeit, Stefan; Hermans-Borgmeyer, Irm; Marescau, Bart; Heerschap, Arend; Isbrandt, Dirk

    2013-01-01

    Phosphorylated creatine (Cr) serves as an energy buffer for ATP replenishment in organs with highly fluctuating energy demand. The central role of Cr in the brain and muscle is emphasized by severe neurometabolic disorders caused by Cr deficiency. Common symptoms of inborn errors of creatine synthesis or distribution include mental retardation and muscular weakness. Human mutations in l-arginine:glycine amidinotransferase (AGAT), the first enzyme of Cr synthesis, lead to severely reduced Cr and guanidinoacetate (GuA) levels. Here, we report the generation and metabolic characterization of AGAT-deficient mice that are devoid of Cr and its precursor GuA. AGAT-deficient mice exhibited decreased fat deposition, attenuated gluconeogenesis, reduced cholesterol levels and enhanced glucose tolerance. Furthermore, Cr deficiency completely protected from the development of metabolic syndrome caused by diet-induced obesity. Biochemical analyses revealed the chronic Cr-dependent activation of AMP-activated protein kinase (AMPK), which stimulates catabolic pathways in metabolically relevant tissues such as the brain, skeletal muscle, adipose tissue and liver, suggesting a mechanism underlying the metabolic phenotype. In summary, our results show marked metabolic effects of Cr deficiency via the chronic activation of AMPK in a first animal model of AGAT deficiency. In addition to insights into metabolic changes in Cr deficiency syndromes, our genetic model reveals a novel mechanism as a potential treatment option for obesity and type 2 diabetes mellitus.

  9. Iron deficiency alters megakaryopoiesis and platelet phenotype independent of thrombopoietin.

    Science.gov (United States)

    Evstatiev, Rayko; Bukaty, Adam; Jimenez, Kristine; Kulnigg-Dabsch, Stefanie; Surman, Lidia; Schmid, Werner; Eferl, Robert; Lippert, Kathrin; Scheiber-Mojdehkar, Barbara; Kvasnicka, Hans Michael; Khare, Vineeta; Gasche, Christoph

    2014-05-01

    Iron deficiency is a common cause of reactive thrombocytosis, however, the exact pathways have not been revealed. Here we aimed to study the mechanisms behind iron deficiency-induced thrombocytosis. Within few weeks, iron-depleted diet caused iron deficiency in young Sprague-Dawley rats, as reflected by a drop in hemoglobin, mean corpuscular volume, hepatic iron content and hepcidin mRNA in the liver. Thrombocytosis established in parallel. Moreover, platelets produced in iron deficient animals displayed a higher mean platelet volume and increased aggregation. Bone marrow studies revealed subtle alterations that are suggestive of expansion of megakaryocyte progenitors, an increase in megakaryocyte ploidy and accelerated megakaryocyte differentiation. Iron deficiency did not alter the production of hematopoietic growth factors such as thrombopoietin, interleukin 6 or interleukin 11. Megakaryocytic cell lines grown in iron-depleted conditions exhibited reduced proliferation but increased ploidy and cell size. Our data suggest that iron deficiency increases megakaryopoietic differentiation and alters platelet phenotype without changes in megakaryocyte growth factors, specifically TPO. Iron deficiency-induced thrombocytosis may have evolved to maintain or increase the coagulation capacity in conditions with chronic bleeding. Copyright © 2014 Wiley Periodicals, Inc.

  10. A link between premenopausal iron deficiency and breast cancer malignancy

    International Nuclear Information System (INIS)

    Jian, Jinlong; Li, Jinqing; Huang, Xi; Yang, Qing; Shao, Yongzhao; Axelrod, Deborah; Smith, Julia; Singh, Baljit; Krauter, Stephanie; Chiriboga, Luis; Yang, Zhaoxu

    2013-01-01

    Young breast cancer (BC) patients less than 45 years old are at higher risk of dying from the disease when compared to their older counterparts. However, specific risk factors leading to this poorer outcome have not been identified. One candidate is iron deficiency, as this is common in young women and a clinical feature of young age. In the present study, we used immuno-competent and immuno-deficient mouse xenograft models as well as hemoglobin as a marker of iron status in young BC patients to demonstrate whether host iron deficiency plays a pro-metastatic role. We showed that mice fed an iron-deficient diet had significantly higher tumor volumes and lung metastasis compared to those fed normal iron diets. Iron deficiency mainly altered Notch but not TGF-β and Wnt signaling in the primary tumor, leading to the activation of epithelial mesenchymal transition (EMT). This was revealed by increased expression of Snai1 and decreased expression of E-cadherin. Importantly, correcting iron deficiency by iron therapy reduced primary tumor volume, lung metastasis, and reversed EMT markers in mice. Furthermore, we found that mild iron deficiency was significantly associated with lymph node invasion in young BC patients (p<0.002). Together, our finding indicates that host iron deficiency could be a contributor of poor prognosis in young BC patients

  11. Mutations and phenotype in isolated glycerol kinase deficiency

    Energy Technology Data Exchange (ETDEWEB)

    Walker, A.P.; Muscatelli, F.; Stafford, A.N.; Monaco, A.P. [Inst. of Molecular Medicine, Oxford (United Kingdom)] [and others

    1996-06-01

    We demonstrate that isolated glycerol kinase (GK) deficiency in three families results from mutation of the Xp21 GK gene. GK mutations were detected in four patients with widely differing phenotypes. Patient 1 had a splice-site mutation causing premature termination. His general health was good despite absent GK activity, indicating that isolated GK deficiency can be silent. Patient 2 had GK deficiency and a severe phenotype involving psychomotor retardation and growth delay, bone dysplasia, and seizures, similar to the severe phenotype of one of the first described cases of GK deficiency. His younger brother, patient 3, also had GK deficiency, but so far his development has been normal. GK exon 17 was deleted in both brothers, implicating additional factors in causation of the severe phenotype of patient 2. Patient 4 had both GK deficiency with mental retardation and a GK missense mutation (D440V). Possible explanations for the phenotypic variation of these four patients include ascertainment bias; metabolic or environmental stress as a precipitating factor in revealing GK-related changes, as has previously been described in juvenile GK deficiency; and interactions with functional polymorphisms in other genes that alter the effect of GK deficiency on normal development. 36 refs., 4 figs., 1 tab.

  12. Transient Ischemic Attack Caused by Iron Deficiency Anemia

    Directory of Open Access Journals (Sweden)

    Ufuk Emre

    2006-02-01

    Full Text Available Transient Ischemic Attack Caused by Iron Deficiency Anemia Transient ischemic attacks are episodes of transient focal ischemia involving the brain or brainstem. They are commonly two to thirty minutes in duration and lasting less than 24 hours. Anemia of iron deficiency isn’t frequently cause for transient ischemic attack. It has been reported as a risk factor for childhood ischemic strokes. In the iron deficiency anemia, T‹A may develop as result of hypercoagulable state and increased viscosity that is caused by anemic hypoxia that is result of reduce hemoglobine level, seconder thrombosis and microcytose As iron deficiency anemia has been reported so rarely in adult patients with transient ischemic attacks as a cause, we aimed to discuss the clinical and outcome features of two cases with iron deficiency anemia and transient ischemic attacks in this study. Materials and methods: Routine neurologic examination, biochemical screen, serological tests, vasculitic markers, thyroid function tests, vitamin B 12 level, cranial imaging, vertebral carotid doppler USG examination was conducted in the two patients. Anemia of iron deficiency was found as the only risk factor for TIA and the two patients were treated with replacement of iron and antiagregan therapy. Neurological examination revealed no abnormality through the two years of follow-up. The iron deficiency anemia may be cause of many neurologic problems such a irritability, lethargy, headache, development retardation except from T‹A. In the iron deficiency anemia, early diagnosis and treatment is important

  13. Purine nucleoside phosphorylase deficiency in two unrelated Saudi patients

    International Nuclear Information System (INIS)

    Alangari, Abdullah; AlHarbi, Abdullah; AlGhonaium Abdulaziz; Santisteban, Ines; Hershfield, Michael

    2009-01-01

    Purine nucleoside phosphorylase (PNP) deficiency is a rare autosomal recessive metabolic disorder that results in combined immunodeficiency, neurologic dysfunction and autoimmunity. PNP deficiency has never been reported from Saudi Arabia or in patients with an Arabic ethnic background. We report on two Saudi girls with PNP deficiency. Both showed severe lymphopenia and neurological involvement. Sequencing of the PNP gene of one girl revealed a novel missense mutation Pro146>Leu in exon 4 due to a change in the codon from CCT>CTT. Expression of PNP (146L) cDNA in E coli indicated that the mutation greatly reduced, but did not completely eliminate PNP activity. (author)

  14. Pseudoachondroplasia with immune deficiency

    International Nuclear Information System (INIS)

    Kultursay, N.; Taneli, B.; Cavusoglu, A.

    1988-01-01

    A 5-year old boy was admitted to the hospital with failure to thrive since he was 2 years old, with weakness in his legs and a waddling gait. He has normal mental development. His parents are normal phenotypically and are unrelated. In analysing his pedigree only a grandfather is described to have waddling gait. He has a normal craniofacial appearance but a disproportionate body with normal trunk and short extremities with height below the 3rd percentile. The diagnosis of pseudoachondroplasia was made on clinical, radiological and laboratory findings. He also had immune deficiency characterised by low T-lymphocyte populations and a low level of serum immunoglobulin A. (orig.)

  15. Primary Carnitine Deficiency

    DEFF Research Database (Denmark)

    Rasmussen, Jan; Hougaard, David M; Sandhu, Noreen

    2017-01-01

    Primary carnitine deficiency (PCD) causes low levels of carnitine in patients potentially leading to metabolic and cardiac symptoms. Newborn screening for PCD is now routine in many countries by measuring carnitine levels in infants. In this study we report Apgar scores, length and weight...... scores, length and weight compared to controls. Newborns with PCD and newborns born to mothers with PCD had significantly lower levels of free carnitine (fC0) than controls. Screening algorithms focusing only on fC0 had a high rate of detection of newborns with PCD. Sample collection 4-9 days after birth...

  16. Glucose-6-phosphatase deficiency

    Directory of Open Access Journals (Sweden)

    Labrune Philippe

    2011-05-01

    Full Text Available Abstract Glucose-6-phosphatase deficiency (G6P deficiency, or glycogen storage disease type I (GSDI, is a group of inherited metabolic diseases, including types Ia and Ib, characterized by poor tolerance to fasting, growth retardation and hepatomegaly resulting from accumulation of glycogen and fat in the liver. Prevalence is unknown and annual incidence is around 1/100,000 births. GSDIa is the more frequent type, representing about 80% of GSDI patients. The disease commonly manifests, between the ages of 3 to 4 months by symptoms of hypoglycemia (tremors, seizures, cyanosis, apnea. Patients have poor tolerance to fasting, marked hepatomegaly, growth retardation (small stature and delayed puberty, generally improved by an appropriate diet, osteopenia and sometimes osteoporosis, full-cheeked round face, enlarged kydneys and platelet dysfunctions leading to frequent epistaxis. In addition, in GSDIb, neutropenia and neutrophil dysfunction are responsible for tendency towards infections, relapsing aphtous gingivostomatitis, and inflammatory bowel disease. Late complications are hepatic (adenomas with rare but possible transformation into hepatocarcinoma and renal (glomerular hyperfiltration leading to proteinuria and sometimes to renal insufficiency. GSDI is caused by a dysfunction in the G6P system, a key step in the regulation of glycemia. The deficit concerns the catalytic subunit G6P-alpha (type Ia which is restricted to expression in the liver, kidney and intestine, or the ubiquitously expressed G6P transporter (type Ib. Mutations in the genes G6PC (17q21 and SLC37A4 (11q23 respectively cause GSDIa and Ib. Many mutations have been identified in both genes,. Transmission is autosomal recessive. Diagnosis is based on clinical presentation, on abnormal basal values and absence of hyperglycemic response to glucagon. It can be confirmed by demonstrating a deficient activity of a G6P system component in a liver biopsy. To date, the diagnosis is most

  17. Mathematics revealed

    CERN Document Server

    Berman, Elizabeth

    1979-01-01

    Mathematics Revealed focuses on the principles, processes, operations, and exercises in mathematics.The book first offers information on whole numbers, fractions, and decimals and percents. Discussions focus on measuring length, percent, decimals, numbers as products, addition and subtraction of fractions, mixed numbers and ratios, division of fractions, addition, subtraction, multiplication, and division. The text then examines positive and negative numbers and powers and computation. Topics include division and averages, multiplication, ratios, and measurements, scientific notation and estim

  18. Iron deficiency anemia and megaloblastic anemia in obese patients.

    Science.gov (United States)

    Arshad, Mahmoud; Jaberian, Sara; Pazouki, Abdolreza; Riazi, Sajedeh; Rangraz, Maryam Aghababa; Mokhber, Somayyeh

    2017-03-01

    The association between obesity and different types of anemia remained uncertain. The present study aimed to assess the relation between obesity parameters and the occurrence of iron deficiency anemia and also megaloblastic anemia among Iranian population. This cross-sectional study was performed on 1252 patients with morbid obesity that randomly selected from all patients referred to Clinic of obesity at Rasoul-e-Akram Hospital in 2014. The morbid obesity was defined according to the guideline as body mass index (BMI) equal to or higher than 40 kg/m2. Various laboratory parameters including serum levels of hemoglobin, iron, ferritin, folic acid, and vitamin B12 were assessed using the standard laboratory techniques. BMI was adversely associated with serum vitamin B12, but not associated with other hematologic parameters. The overall prevalence of iron deficiency anemia was 9.8%. The prevalence of iron deficiency anemia was independent to patients' age and also to body mass index. The prevalence of vitamin B12 deficiency was totally 20.9%. According to the multivariable logistic regression model, no association was revealed between BMI and the occurrence of iron deficiency anemia adjusting gender and age. A similar regression model showed that higher BMI could predict occurrence of vitamin B12 deficiency in morbid obese patients. Although iron deficiency is a common finding among obese patients, vitamin B12 deficiency is more frequent so about one-fifth of these patients suffer vitamin B12 deficiency. In fact, the exacerbation of obesity can result in exacerbation of vitamin B12 deficiency.

  19. [Vitamin deficiencies in breastfed children due to maternal dietary deficiency

    NARCIS (Netherlands)

    Kollee, L.A.A.

    2006-01-01

    Dietary deficiencies of vitamin B12 and vitamin D during pregnancy and lactation may result in health problems in exclusively breastfed infants. Vitamin-B12 deficiency in these infants results in irritability, anorexia and failure to thrive during the first 4-8 months of life. Severe and permanent

  20. Molecular characterization of FXI deficiency.

    Science.gov (United States)

    Berber, Ergul

    2011-02-01

    Factor XI (FXI) deficiency is a rare autosomal bleeding disease associated with genetic defects in the FXI gene. It is a heterogeneous disorder with variable tendency in bleeding and variable causative FXI gene mutations. It is characterized as a cross-reacting material-negative (CRM-) FXI deficiency due to decreased FXI levels or cross-reacting material-positive (CRM+) FXI deficiency due to impaired FXI function. Increasing number of mutations has been reported in FXI mutation database, and most of the mutations are affecting serine protease (SP) domain of the protein. Functional characterization for the mutations helps to better understand the molecular basis of FXI deficiency. Prevalence of the disease is higher in certain populations such as Ashkenazi Jews. The purpose of this review is to give an overview of the molecular basis of congenital FXI deficiency.

  1. Deficiencies in radiation protection record systems

    International Nuclear Information System (INIS)

    Martin, J.B.; Lyon, M.

    1991-01-01

    Radiation protection records are a fundamental part of any program for protecting radiation workers. Records are essential to epidemiological studies of radiation workers and are becoming increasingly important as the number of radiation exposure litigation cases increases. Ready retrievability of comprehensive records is also essential to the adequate defense of a radiation protection program. Appraisals of numerous radiation protection programs have revealed that few record-keeping systems comply with American National Standards Institute, Standard Practice N13.6-1972. Record-keeping requirements and types of deficiencies in radiation protection records systems are presented in this paper, followed by general recommendations for implementing a comprehensive radiation protection records system

  2. Deficiencies in radiation protection record systems

    International Nuclear Information System (INIS)

    Martin, J.B.; Lyon, M.

    1991-01-01

    Radiation protection records are a fundamental part of any program for protecting radiation workers. Records are essential to epidemiological studies of radiation workers and are becoming increasingly important as the number of radiation exposure litigation cases increases. Ready retrievability of comprehensive records is also essential to the adequate defense of a radiation protection program. Appraisals of numerous radiation protection programs have revealed that few record-keeping systems comply with American National Standards Institute, Standard Practice N13.6-1972. Record-keeping requirements and types of deficiencies in radiation protection records systems are presented in this paper, followed by general recommendations for implementing a comprehensive radiation protection records system. 8 refs

  3. Revealing Rembrandt

    Directory of Open Access Journals (Sweden)

    Andrew J Parker

    2014-04-01

    Full Text Available The power and significance of artwork in shaping human cognition is self-evident. The starting point for our empirical investigations is the view that the task of neuroscience is to integrate itself with other forms of knowledge, rather than to seek to supplant them. In our recent work, we examined a particular aspect of the appreciation of artwork using present-day functional magnetic resonance imaging (fMRI. Our results emphasised the continuity between viewing artwork and other human cognitive activities. We also showed that appreciation of a particular aspect of artwork, namely authenticity, depends upon the co-ordinated activity between the brain regions involved in multiple decision making and those responsible for processing visual information. The findings about brain function probably have no specific consequences for understanding how people respond to the art of Rembrandt in comparison with their response to other artworks. However, the use of images of Rembrandt’s portraits, his most intimate and personal works, clearly had a significant impact upon our viewers, even though they have been spatially confined to the interior of an MRI scanner at the time of viewing. Neuroscientific studies of humans viewing artwork have the capacity to reveal the diversity of human cognitive responses that may be induced by external advice or context as people view artwork in a variety of frameworks and settings.

  4. Genetics Home Reference: factor VII deficiency

    Science.gov (United States)

    ... Facebook Twitter Home Health Conditions Factor VII deficiency Factor VII deficiency Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Factor VII deficiency is a rare bleeding disorder that varies ...

  5. Monocular Elevation Deficiency - Double Elevator Palsy

    Science.gov (United States)

    ... Español Condiciones Chinese Conditions Monocular Elevation Deficiency/ Double Elevator Palsy En Español Read in Chinese What is monocular elevation deficiency (Double Elevator Palsy)? Monocular Elevation Deficiency, also known by the ...

  6. Genetics Home Reference: CDKL5 deficiency disorder

    Science.gov (United States)

    ... Facebook Twitter Home Health Conditions CDKL5 deficiency disorder CDKL5 deficiency disorder Printable PDF Open All Close All ... Javascript to view the expand/collapse boxes. Description CDKL5 deficiency disorder is characterized by seizures that begin ...

  7. Genetics Home Reference: tyrosine hydroxylase deficiency

    Science.gov (United States)

    ... Email Facebook Twitter Home Health Conditions TH deficiency Tyrosine hydroxylase deficiency Printable PDF Open All Close All ... Javascript to view the expand/collapse boxes. Description Tyrosine hydroxylase (TH) deficiency is a disorder that primarily ...

  8. Deficiency and toxicity of boron: Alterations in growth, oxidative damage and uptake by citrange orange plants.

    Science.gov (United States)

    Shah, Asad; Wu, Xiuwen; Ullah, Abid; Fahad, Shah; Muhammad, Riaz; Yan, Lei; Jiang, Cuncang

    2017-11-01

    Boron (B) deficiency and toxicity are the major factors that affect plant growth and yield. The present study revealed the effect of B deficiency and toxicity on plant growth, morphology, physiology, and cell structure. A hydroponic culture experiment was conducted with five B levels, B deficient (B0), sufficient (B20, B10, B40) and toxic (B100). Our results show that both B deficient as well as excess level inhibit plant growth. In B deficiency, the major visible symptoms were appeared in roots, while B excess burned the leaf margin of older leaves. The antioxidant enzymes including superoxide dismutase (SOD), peroxidase (POD), catalase (CAT) and ascorbate peroxidase (APX) decreased at B deficiency and also decreased up to some extent at B excess, while in sufficient treatments, the higher antioxidant enzymes were found at B20. In addition, the MDA concentration decreased at B deficiency and increased with B concentration. Moreover, the photosynthetic rate, transpiration rate, stomatal conductance, leaf gas exchange and intercellular CO 2 were reduced at both B deficiency as well as excess and higher at sufficient B20 treatment significantly. The chlorophyll and carotenoid content increased at B20 treatment, while decreased at B deficiency and excess. The middle lamellae of cell wall were found thick at B excess and normal at B20. The current study revealed that B deficiency as well as excess concentration affect plant growth and various morpho-physiological processes. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Mortality and GH deficiency

    DEFF Research Database (Denmark)

    Stochholm, Kirstine; Gravholt, Claus Højbjerg; Laursen, Torben

    2007-01-01

    into childhood onset (CO) and adult onset (AO), discriminated by an age cutoff below or above 18 years at onset of GHD. METHOD: Data on death were identified in national registries. Sex- and cause-specific mortalities were identified in CO and AO GHD when compared with controls. RESULTS: Mortality was increased......OBJECTIVE: To estimate the mortality in Denmark in patients suffering from GH deficiency (GHD). DESIGN: Mortality was analyzed in 1794 GHD patients and 8014 controls matched on age and gender. All records in GHD patients were studied and additional morbidity noted. Patients were divided...... in CO and AO GHD in both genders, when compared with controls. The hazard ratio (HR) for CO males was 8.3 (95% confidence interval (CI) 4.5-15.1) and for females 9.4 (CI 4.6-19.4). For AO males, HR was 1.9 (CI 1.7-2.2) and for females 3.4 (CI 2.9-4.0). We found a significantly higher HR in AO females...

  10. Iron deficiency - a global problem

    International Nuclear Information System (INIS)

    Ali, S.M.

    1993-01-01

    Iron deficiency is an important nutritional global problem. This paper contains summery of information gathered from a dietary survey as iron deficiency anaemia is major public health problem in many developing countries including Pakistan. Comparison of anaemia in different age group and sex versus various regions in the world are given. In Pakistan also anaemia is widespread. According to the report of Micro-Nutrient survey of Pakistan 40% of the population are found to have low level of haemoglobin, more than half of pregnant women suffered from marginal or deficient haemoglobin. (A.B.)

  11. Iron deficiency - a global problem

    Energy Technology Data Exchange (ETDEWEB)

    Ali, S M [Pakistan Council for Science and Technology, Islamabad (Pakistan)

    1994-12-31

    Iron deficiency is an important nutritional global problem. This paper contains summery of information gathered from a dietary survey as iron deficiency anaemia is major public health problem in many developing countries including Pakistan. Comparison of anaemia in different age group and sex versus various regions in the world are given. In Pakistan also anaemia is widespread. According to the report of Micro-Nutrient survey of Pakistan 40% of the population are found to have low level of haemoglobin, more than half of pregnant women suffered from marginal or deficient haemoglobin. (A.B.).

  12. Genetics Home Reference: corticosterone methyloxidase deficiency

    Science.gov (United States)

    ... hyperreninemic hypoaldosteronism steroid 18-hydroxylase deficiency steroid 18-oxidase deficiency Visser-Cost syndrome ... Potassium Test Health Topic: Adrenal Gland Disorders Health Topic: Fluid ...

  13. Myopathy and hepatic lipidosis in weaned lambs due to vitamin E deficiency.

    Science.gov (United States)

    Menzies, Paula; Langs, Lisa; Boermans, Herman; Martin, John; McNally, John

    2004-03-01

    A sheep flock experienced losses in weaned lambs from myopathy and hepatic lipidosis. Investigation revealed painful ambulation, illthrift, and unexpected death in lambs with normal selenium levels, deficient vitamin E levels, and elevated muscle and liver enzyme levels. Vitamin E deficiency should be considered when investigating myopathy and illthrift in lambs.

  14. Myopathy and hepatic lipidosis in weaned lambs due to vitamin E deficiency

    OpenAIRE

    Menzies, Paula; Langs, Lisa; Boermans, Herman; Martin, John; McNally, John

    2004-01-01

    A sheep flock experienced losses in weaned lambs from myopathy and hepatic lipidosis. Investigation revealed painful ambulation, illthrift, and unexpected death in lambs with normal selenium levels, deficient vitamin E levels, and elevated muscle and liver enzyme levels. Vitamin E deficiency should be considered when investigating myopathy and illthrift in lambs.

  15. Human alpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency: no association with neuroaxonal dystrophy?

    NARCIS (Netherlands)

    Bakker, H. D.; de Sonnaville, M. L.; Vreken, P.; Abeling, N. G.; Groener, J. E.; Keulemans, J. L.; van Diggelen, O. P.

    2001-01-01

    Two new individuals with alpha-NAGA deficiency are presented. The index patient, 3 years old, has congenital cataract, slight motor retardation and secondary demyelinisation. Screening of his sibs revealed an alpha-NAGA deficiency in his 7-year-old healthy brother who had no clinical or neurological

  16. Familial LCAT deficiency: from renal replacement to enzyme replacement

    NARCIS (Netherlands)

    Stoekenbroek, R. M.; van den Bergh Weerman, M. A.; Hovingh, G. K.; Potter van Loon, B. J.; Siegert, C. E. H.; Holleboom, A. G.

    2013-01-01

    Familial LCAT deficiency (FLD) is a recessive lipid disorder ultimately leading to end-stage renal disease (ESRD). We present two brothers with considerable variation in the age at which they developed ESRD. Kidney biopsies revealed both tubular and glomerular pathology. To date, no causal therapy

  17. Vena porta thrombosis in patient with inherited factor VII deficiency

    DEFF Research Database (Denmark)

    Klovaite, Jolanta; Friis-Hansen, Lennart Jan; Larsen, Fin S

    2010-01-01

    with inherited FVII deficiency and chronic vena porta thrombosis. She presented at 32 weeks of gestation with spontaneously increased international normalized ratio, severe thrombocytopenia and very few unspecific symptoms. The extensive examination of the patient revealed cavernous transformation of the portal...

  18. Genetics Home Reference: aromatase deficiency

    Science.gov (United States)

    ... to impaired female sexual development, unusual bone growth, insulin resistance, and other signs and symptoms of aromatase deficiency . In women who are pregnant with an affected fetus, excess androgens in the ...

  19. Genetics Home Reference: fumarase deficiency

    Science.gov (United States)

    ... V, Tomlinson IP. The FH mutation database: an online database of fumarate hydratase mutations involved in the MCUL (HLRCC) tumor syndrome and congenital fumarase deficiency. BMC Med Genet. 2008 Mar 25;9:20. doi: 10.1186/1471-2350- ...

  20. Genetics Home Reference: proopiomelanocortin deficiency

    Science.gov (United States)

    ... are constantly hungry, which leads to excessive feeding (hyperphagia). The babies continuously gain weight and are severely ... brain dysregulates the body's energy balance, leading to overeating and severe obesity. POMC deficiency is a rare ...

  1. Factor XII (Hageman factor) deficiency

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000545.htm Factor XII (Hageman factor) deficiency To use the sharing features on this ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  2. ALPHA,·ANTITRYPSIN DEFICIENCY*

    African Journals Online (AJOL)

    1971-02-06

    Feb 6, 1971 ... bited proteolytic enzymatic proce.s which is able to pro- duce type A ... homozygous a!pha,-antitrypsin deficiency associated with severe obstructive .... in digestion of alveolar septa producing panacinar em- physema or type A ...

  3. Iron deficiency among blood donors

    DEFF Research Database (Denmark)

    Rigas, A S; Pedersen, O B; Magnussen, K

    2017-01-01

    Blood components collected from blood donors are an invaluable part of modern-day medicine. A healthy blood donor population is therefore of paramount importance. The results from the Danish Blood Donor Study (DBDS) indicate that gender, number of previous donations, time since last donation...... and menopausal status are the strongest predictors of iron deficiency. Only little information on the health effects of iron deficiency in blood donors exits. Possibly, after a standard full blood donation, a temporarily reduced physical performance for women is observed. However, iron deficiency among blood...... donors is not reflected in a reduced self-perceived mental and physical health. In general, the high proportion of iron-deficient donors can be alleviated either by extending the inter-donation intervals or by guided iron supplementation. The experience from Copenhagen, the Capital Region of Denmark...

  4. Gender affects skin wound healing in plasminogen deficient mice.

    Directory of Open Access Journals (Sweden)

    Birgitte Rønø

    Full Text Available The fibrinolytic activity of plasmin plays a fundamental role in resolution of blood clots and clearance of extravascular deposited fibrin in damaged tissues. These vital functions of plasmin are exploited by malignant cells to accelerate tumor growth and facilitate metastases. Mice lacking functional plasmin thus display decreased tumor growth in a variety of cancer models. Interestingly, this role of plasmin has, in regard to skin cancer, been shown to be restricted to male mice. It remains to be clarified whether gender also affects other phenotypic characteristics of plasmin deficiency or if this gender effect is restricted to skin cancer. To investigate this, we tested the effect of gender on plasmin dependent immune cell migration, accumulation of hepatic fibrin depositions, skin composition, and skin wound healing. Gender did not affect immune cell migration or hepatic fibrin accumulation in neither wildtype nor plasmin deficient mice, and the existing differences in skin composition between males and females were unaffected by plasmin deficiency. In contrast, gender had a marked effect on the ability of plasmin deficient mice to heal skin wounds, which was seen as an accelerated wound closure in female versus male plasmin deficient mice. Further studies showed that this gender effect could not be reversed by ovariectomy, suggesting that female sex-hormones did not mediate the accelerated skin wound healing in plasmin deficient female mice. Histological examination of healed wounds revealed larger amounts of fibrotic scars in the provisional matrix of plasmin deficient male mice compared to female mice. These fibrotic scars correlated to an obstruction of cell infiltration of the granulation tissue, which is a prerequisite for wound healing. In conclusion, the presented data show that the gender dependent effect of plasmin deficiency is tissue specific and may be secondary to already established differences between genders, such as skin

  5. Deficiency of Carbonic Anhydrase II Results in a Urinary Concentrating Defect

    DEFF Research Database (Denmark)

    Krishnan, Devishree; Pan, Wanling; Beggs, Megan R

    2018-01-01

    (TDL); however, the physiological role of a CAII-AQP1 interaction in this nephron segment is not known. To determine if CAII was required for urinary concentration, we studied water handling in CAII-deficient mice. CAII-deficient mice demonstrate polyuria and polydipsia as well as an alkaline urine...... and bicarbonaturia, consistent with a type III renal tubular acidosis. Natriuresis and hypercalciuria cause polyuria, however, CAII-deficient mice did not have increased urinary sodium nor calcium excretion. Further examination revealed dilute urine in the CAII-deficient mice. Urinary concentration remained reduced...

  6. Combined pituitary hormone deficiency in a girl with 48, XXXX and Rathke's cleft cyst.

    Science.gov (United States)

    Uppal, Surabhi; Jee, Youn Hee; Lightbourne, Marissa; Han, Joan C; Stratakis, Constantine A

    2017-01-01

    Tetrasomy X is a rare chromosomal aneuploidy seen in girls, associated with facial dysmorphism, premature ovarian insufficiency and intellectual disability. A Rathke's cleft cyst (RCC) is a remnant of Rathke's pouch which may cause multiple pituitary hormone deficiencies by exerting pressure on the pituitary gland in the sella. The patient was diagnosed with tetrasomy X by karyotyping during infancy. Brain MRI and multiple endocrine stimulation tests revealed RCC and combined pituitary hormone deficiency (growth hormone deficiency, secondary adrenal insufficiency and central hypothyroidism) likely due to RCC. We report the first case in the literature of a girl with 48, XXXX and combined pituitary hormone deficiency due to Rathke's cyst.

  7. Combined Respiratory Chain Deficiency and UQCC2 Mutations in Neonatal Encephalomyopathy: Defective Supercomplex Assembly in Complex III Deficiencies

    Directory of Open Access Journals (Sweden)

    René G. Feichtinger

    2017-01-01

    Full Text Available Vertebrate respiratory chain complex III consists of eleven subunits. Mutations in five subunits either mitochondrial (MT-CYB or nuclear (CYC1, UQCRC2, UQCRB, and UQCRQ encoded have been reported. Defects in five further factors for assembly (TTC19, UQCC2, and UQCC3 or iron-sulphur cluster loading (BCS1L and LYRM7 cause complex III deficiency. Here, we report a second patient with UQCC2 deficiency. This girl was born prematurely; pregnancy was complicated by intrauterine growth retardation and oligohydramnios. She presented with respiratory distress syndrome, developed epileptic seizures progressing to status epilepticus, and died at day 33. She had profound lactic acidosis and elevated urinary pyruvate. Exome sequencing revealed two homozygous missense variants in UQCC2, leading to a severe reduction of UQCC2 protein. Deficiency of complexes I and III was found enzymatically and on the protein level. A review of the literature on genetically distinct complex III defects revealed that, except TTC19 deficiency, the biochemical pattern was very often a combined respiratory chain deficiency. Besides complex III, typically, complex I was decreased, in some cases complex IV. In accordance with previous observations, the presence of assembled complex III is required for the stability or assembly of complexes I and IV, which might be related to respirasome/supercomplex formation.

  8. Anemia, Iron Deficiency and Iodine Deficiency among Nepalese School Children.

    Science.gov (United States)

    Khatiwada, Saroj; Lamsal, Madhab; Gelal, Basanta; Gautam, Sharad; Nepal, Ashwini Kumar; Brodie, David; Baral, Nirmal

    2016-07-01

    To assess iodine and iron nutritional status among Nepalese school children. A cross-sectional, community based study was conducted in the two districts, Ilam (hilly region) and Udayapur (plain region) of eastern Nepal. A total of 759 school children aged 6-13 y from different schools within the study areas were randomly enrolled. A total of 759 urine samples and 316 blood samples were collected. Blood hemoglobin level, serum iron, total iron binding capacity and urinary iodine concentration was measured. Percentage of transferrin saturation was calculated using serum iron and total iron binding capacity values. The mean level of hemoglobin, serum iron, total iron binding capacity, transferrin saturation and median urinary iodine excretion were 12.29 ± 1.85 g/dl, 70.45 ± 34.46 μg/dl, 386.48 ± 62.48 μg/dl, 19.94 ± 12.07 % and 274.67 μg/L respectively. Anemia, iron deficiency and iodine deficiency (urinary iodine excretion iron deficient children. Iron deficiency and anemia are common in Nepalese children, whereas, iodine nutrition is more than adequate. Low urinary iodine excretion was common in iron deficiency and anemia.

  9. Iron-Deficiency Anemia (For Parents)

    Science.gov (United States)

    ... Videos for Educators Search English Español Iron-Deficiency Anemia KidsHealth / For Parents / Iron-Deficiency Anemia What's in ... common nutritional deficiency in children. About Iron-Deficiency Anemia Every red blood cell in the body contains ...

  10. Hereditary protein S deficiency presenting with cerebral sinus thrombosis in an adolescent girl

    NARCIS (Netherlands)

    Koelman, J. H.; Bakker, C. M.; Plandsoen, W. C.; Peeters, F. L.; Barth, P. G.

    1992-01-01

    A 14-year-old girl, on oral contraceptives for 3 months, presented with cerebral sinus thrombosis. Investigation revealed underlying hereditary protein S deficiency. This uncommon cause of cerebral sinus thrombosis and the possible association with oral contraceptives are discussed

  11. Iron deficiency and anemia: a common problem in female elite soccer players.

    Science.gov (United States)

    Landahl, Göran; Adolfsson, Peter; Börjesson, Mats; Mannheimer, Clas; Rödjer, Stig

    2005-12-01

    The objective of the study was to determine the prevalence of iron deficiency and iron deficiency anemia among elite women soccer players. Hemoglobin, serum iron, serum total iron binding capacity, and ferritin were determined in 28 female soccer players called up for the national team. Of the investigated female soccer players, 57% had iron deficiency and 29% iron deficiency anemia 6 months before the FIFA Women's World Cup. It is concluded that iron deficiency and iron deficiency anemia is common in female soccer players at the top international level. Some might suffer from relative anemia and measurement of hemoglobin alone is not sufficient to reveal relative anemia. Regular monitoring of hemoglobin concentration and iron status is necessary to institute iron supplementation when indicated.

  12. Adipose tissue deficiency of hormone-sensitive lipase causes fatty liver in mice.

    Science.gov (United States)

    Xia, Bo; Cai, Guo He; Yang, Hao; Wang, Shu Pei; Mitchell, Grant A; Wu, Jiang Wei

    2017-12-01

    Fatty liver is a major health problem worldwide. People with hereditary deficiency of hormone-sensitive lipase (HSL) are reported to develop fatty liver. In this study, systemic and tissue-specific HSL-deficient mice were used as models to explore the underlying mechanism of this association. We found that systemic HSL deficient mice developed fatty liver in an age-dependent fashion between 3 and 8 months of age. To further explore the mechanism of fatty liver in HSL deficiency, liver-specific HSL knockout mice were created. Surprisingly, liver HSL deficiency did not influence liver fat content, suggesting that fatty liver in HSL deficiency is not liver autonomous. Given the importance of adipose tissue in systemic triglyceride metabolism, we created adipose-specific HSL knockout mice and found that adipose HSL deficiency, to a similar extent as systemic HSL deficiency, causes age-dependent fatty liver in mice. Mechanistic study revealed that deficiency of HSL in adipose tissue caused inflammatory macrophage infiltrates, progressive lipodystrophy, abnormal adipokine secretion and systemic insulin resistance. These changes in adipose tissue were associated with a constellation of changes in liver: low levels of fatty acid oxidation, of very low density lipoprotein secretion and of triglyceride hydrolase activity, each favoring the development of hepatic steatosis. In conclusion, HSL-deficient mice revealed a complex interorgan interaction between adipose tissue and liver: the role of HSL in the liver is minimal but adipose tissue deficiency of HSL can cause age-dependent hepatic steatosis. Adipose tissue is a potential target for treating the hepatic steatosis of HSL deficiency.

  13. Iodine deficiency and thyroid disorders.

    Science.gov (United States)

    Zimmermann, Michael B; Boelaert, Kristien

    2015-04-01

    Iodine deficiency early in life impairs cognition and growth, but iodine status is also a key determinant of thyroid disorders in adults. Severe iodine deficiency causes goitre and hypothyroidism because, despite an increase in thyroid activity to maximise iodine uptake and recycling in this setting, iodine concentrations are still too low to enable production of thyroid hormone. In mild-to-moderate iodine deficiency, increased thyroid activity can compensate for low iodine intake and maintain euthyroidism in most individuals, but at a price: chronic thyroid stimulation results in an increase in the prevalence of toxic nodular goitre and hyperthyroidism in populations. This high prevalence of nodular autonomy usually results in a further increase in the prevalence of hyperthyroidism if iodine intake is subsequently increased by salt iodisation. However, this increase is transient because iodine sufficiency normalises thyroid activity which, in the long term, reduces nodular autonomy. Increased iodine intake in an iodine-deficient population is associated with a small increase in the prevalence of subclinical hypothyroidism and thyroid autoimmunity; whether these increases are also transient is unclear. Variations in population iodine intake do not affect risk for Graves' disease or thyroid cancer, but correction of iodine deficiency might shift thyroid cancer subtypes toward less malignant forms. Thus, optimisation of population iodine intake is an important component of preventive health care to reduce the prevalence of thyroid disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Emphysema and bronchiectasis secondary to alpha-1 antitrypsin deficiency

    International Nuclear Information System (INIS)

    Fahim, A.; Hart, S.P.; Wilmot, R.

    2013-01-01

    A 47-year-old Caucasian male presented to the chest clinic with a 4-week history of exertional dyspnea. A chest radiograph showed mild hyperinflation without any focal pathology and spirometry showed a mild obstructive defect. In view of symptoms being disproportionate to spirometric and radiologic abnormalities, a thoracic CT scan was obtained. It revealed that there was evidence of bronchiectasis and mild emphysema in basal distribution. Subsequently, he was confirmed to have severe 1-Antitrypsin deficiency. This case illustrates the importance of considering 1-Antitrypsin deficiency in patients with combination of emphysema and bronchiectasis in a basal distribution. Although basal emphysema is well recognized pulmonary manifestation of 1-Antitrypsin deficiency, it is extremely unusual to have bronchiectasis with very mild degree of emphysema. (author)

  15. Tuberculosis and the acquired immune deficiency syndrome in South Brazil

    International Nuclear Information System (INIS)

    Vieira, M.V.; Genro, C.H.; Santos Silveira, R. de C. dos

    1989-01-01

    Tuberculosis and the acquired immune deficiency syndrome in South Brazil. The authors studied the incidence of tuberculosis in South Brazilian patients with acquired immune deficiency syndrome from January 1985 to June 1988. During this period, tuberculosis occurred in 10.3% of acquired immune deficiency syndrome patients. The socioeconomic conditions and the incidence of disease in the population were not confirmed as a potential risk for tuberculosis infection. Chest radiographs revealed pulmonary infiltrates in six patients, hilar and/or mediastinal adenopathy in three, and pleural effusion in two. The two remaining patients had pulmonary consolidation associated with other features. None of these patients presented pulmonary cavitation or radiographic findings of typical reactivation of pulmonary tuberculosis. (author) [pt

  16. Androgen deficiency in the aging male and chronic prostatitis: clinical and diagnostic comparative analysis

    Directory of Open Access Journals (Sweden)

    Spirin Р.V.

    2013-03-01

    Full Text Available The research goal is to study probability, period of development and characteristics of a clinical course of chronic prostatitis against the background of androgen deficiency in the aging male. Materials and methods: The Aging Male Symptoms (AMS rating scale has been applied for androgen deficiency evaluation and the International Prostate Symptom Score (IPSS — for chronic prostatitis evaluation. 57 men with chronic prostatitis in combination with androgen deficiency in the aging male have been examined. Results: It has been concluded that the development of chronic prostatitis against the background of androgen deficiency in the aging male occurs in a shorter time period and about 1.5 times more frequently compared to androgen deficiency in the aging male at the background of chronic prostatitis. The analysis of time periods between the onset of chronic prostatitis symptoms against the background of androgen deficiency in the aging male and androgen deficiency in the aging male symptoms against the background of chronic prostatitis showed that androgen deficiency in the aging male symptoms have been revealed 1-2 years earlier than the onset of chronic prostatitis. The development of androgen deficiency in the aging male against the background of chronic prostatitis has showed a backward tendency. Signs of chronic prostatitis have been more frequently occurred in a period of four-five years earlier the androgen deficiency in the aging male development. Conclusion: The risk of development of chronic prostatitis against the background of androgen deficiency in the aging male during the next two years is actually four times higher in comparison with the development of androgen deficiency in the aging male against the background of chronic prostatitis. According to the International Prostate Symptom Score (IPSS, patients with chronic prostatitis in combination with androgen deficiency in the aging male showed higher degree of severity than

  17. Iron deficiency in blood donors

    Directory of Open Access Journals (Sweden)

    Rodolfo Delfini Cançado

    Full Text Available CONTEXT: Blood donation results in a substantial loss of iron (200 to 250 mg at each bleeding procedure (425 to 475 ml and subsequent mobilization of iron from body stores. Recent reports have shown that body iron reserves generally are small and iron depletion is more frequent in blood donors than in non-donors. OBJECTIVE: The aim of this study was to evaluate the frequency of iron deficiency in blood donors and to establish the frequency of iron deficiency in blood donors according to sex, whether they were first-time or multi-time donors, and the frequency of donations per year. DESIGN: From September 20 to October 5, 1999, three hundred blood donors from Santa Casa Hemocenter of São Paulo were studied. DIAGNOSTIC TESTS: Using a combination of biochemical measurements of iron status: serum iron, total iron-binding capacity, transferrin saturation index, serum ferritin and the erythrocyte indices. RESULTS: The frequency of iron deficiency in blood donors was 11.0%, of whom 5.5% (13/237 were male and 31.7% (20/63 female donors. The frequency of iron deficiency was higher in multi-time blood donors than in first-time blood donors, for male blood donors (7.6% versus 0.0%, P < 0.05 and female ones (41.5% versus 18.5%, P < 0.05. The frequency of iron deficiency found was higher among the male blood donors with three or more donations per year (P < 0.05 and among the female blood donors with two or more donations per year (P < 0.05. CONCLUSIONS: We conclude that blood donation is a very important factor for iron deficiency in blood donors, particularly in multi-time donors and especially in female donors. The high frequency of blood donors with iron deficiency found in this study suggests a need for a more accurate laboratory trial, as hemoglobin or hematocrit measurement alone is not sufficient for detecting and excluding blood donors with iron deficiency without anemia.

  18. Primary Carnitine (OCTN2) Deficiency Without Neonatal Carnitine Deficiency

    NARCIS (Netherlands)

    Boer, L. de; Kluijtmans, L.A.J.; Morava, E.

    2013-01-01

    Although the diagnosis of a primary carnitine deficiency is usually based on a very low level of free and total carnitine (free carnitine: 1-5 muM, normal 20-55 muM) (Longo et al. 2006), we detected a patient via newborn screening with a total carnitine level 67 % of the normal value. At the age of

  19. Deficiency of employability capacity

    Directory of Open Access Journals (Sweden)

    Pelse I.

    2012-10-01

    Full Text Available Young unemployed people have comprised one of the significantly largest groups of the unemployed people in Latvia in recent years. One of the reasons why young people have difficulty integrating into the labour market is the “expectation gap” that exists in the relations between employers and the new generation of workers. Employers focus on capacity-building for employability such individual factors as strength, patience, self-discipline, self-reliance, self-motivation, etc., which having a nature of habit and are developed in a long-term work socialization process, which begins even before the formal education and will continue throughout the life cycle. However, when the socialization is lost, these habits are depreciated faster than they can be restored. Currently a new generation is entering the labour market, which is missing the succession of work socialization. Factors, such as rising unemployment and poverty in the background over the past twenty years in Latvia have created a very unfavourable employability background of “personal circumstances” and “external factors”, which seriously have impaired formation of the skills and attitudes in a real work environment. The study reveals another paradox – the paradox of poverty. Common sense would want to argue that poverty can be overcome by the job. However, the real state of affairs shows that unfavourable coincidence of the individual, personal circumstances and external factors leads to deficit of employability capacity and possibility of marked social and employment deprivation.

  20. Hyperthyroidism caused by acquired immune deficiency syndrome.

    Science.gov (United States)

    Wang, J-J; Zhou, J-J; Yuan, X-L; Li, C-Y; Sheng, H; Su, B; Sheng, C-J; Qu, S; Li, H

    2014-01-01

    Acquired immune deficiency syndrome (AIDS) is an immune deficiency disease. The etiology of hyperthyroidism, which can also be immune-related, is usually divided into six classical categories, including hypophyseal, hypothalamic, thyroid, neoplastic, autoimmune and inflammatory hyperthyroidism. Hyperthyroidism is a rare complication of highly active antimicrobial therapy (HAART) for human immunodeficiency virus (HIV). Hyperthyroidism caused directly by AIDS has not been previously reported. A 29-year-old man who complained of dyspnea and asthenia for 1 month, recurrent fever for more than 20 days, and breathlessness for 1 week was admitted to our hospital. The thyroid function test showed that the level of free thyroxine (FT4) was higher than normal and that the level of thyroid-stimulating hormone (TSH) was below normal. He was diagnosed with hyperthyroidism. Additional investigations revealed a low serum albumin level and chest infection, along with diffuse lung fibrosis. Within 1 month, he experienced significant weight loss, no hand tremors, intolerance of heat, and perspiration proneness. We recommended an HIV examination; subsequently, AIDS was diagnosed based on the laboratory parameters. This is the first reported case of hyperthyroidism caused by AIDS. AIDS may cause hyperthyroidism by immunization regulation with complex, atypical, and easily ignored symptoms. Although hyperthyroidism is rare in patients with AIDS, clinicians should be aware of this potential interaction and should carefully monitor thyroid function in HIV-positive patients.

  1. Lipidomic and Transcriptomic Basis of Lysosomal Dysfunction in Progranulin Deficiency

    Directory of Open Access Journals (Sweden)

    Bret M. Evers

    2017-09-01

    Full Text Available Defective lysosomal function defines many neurodegenerative diseases, such as neuronal ceroid lipofuscinoses (NCL and Niemann-Pick type C (NPC, and is implicated in Alzheimer’s disease (AD and frontotemporal lobar degeneration (FTLD-TDP with progranulin (PGRN deficiency. Here, we show that PGRN is involved in lysosomal homeostasis and lipid metabolism. PGRN deficiency alters lysosome abundance and morphology in mouse neurons. Using an unbiased lipidomic approach, we found that brain lipid composition in humans and mice with PGRN deficiency shows disease-specific differences that distinguish them from normal and other pathologic groups. PGRN loss leads to an accumulation of polyunsaturated triacylglycerides, as well as a reduction of diacylglycerides and phosphatidylserines in fibroblast and enriched lysosome lipidomes. Transcriptomic analysis of PGRN-deficient mouse brains revealed distinct expression patterns of lysosomal, immune-related, and lipid metabolic genes. These findings have implications for the pathogenesis of FTLD-TDP due to PGRN deficiency and suggest lysosomal dysfunction as an underlying mechanism.

  2. Widespread episodic thiamine deficiency in Northern Hemisphere wildlife

    Science.gov (United States)

    Balk, Lennart; Hägerroth, Per-Åke; Gustavsson, Hanna; Sigg, Lisa; Åkerman, Gun; Ruiz Muñoz, Yolanda; Honeyfield, Dale C.; Tjärnlund, Ulla; Oliveira, Kenneth; Ström, Karin; McCormick, Stephen D.; Karlsson, Simon; Ström, Marika; van Manen, Mathijs; Berg, Anna-Lena; Halldórsson, Halldór P.; Strömquist, Jennie; Collier, Tracy K.; Börjeson, Hans; Mörner, Torsten; Hansson, Tomas

    2016-12-01

    Many wildlife populations are declining at rates higher than can be explained by known threats to biodiversity. Recently, thiamine (vitamin B1) deficiency has emerged as a possible contributing cause. Here, thiamine status was systematically investigated in three animal classes: bivalves, ray-finned fishes, and birds. Thiamine diphosphate is required as a cofactor in at least five life-sustaining enzymes that are required for basic cellular metabolism. Analysis of different phosphorylated forms of thiamine, as well as of activities and amount of holoenzyme and apoenzyme forms of thiamine-dependent enzymes, revealed episodically occurring thiamine deficiency in all three animal classes. These biochemical effects were also linked to secondary effects on growth, condition, liver size, blood chemistry and composition, histopathology, swimming behaviour and endurance, parasite infestation, and reproduction. It is unlikely that the thiamine deficiency is caused by impaired phosphorylation within the cells. Rather, the results point towards insufficient amounts of thiamine in the food. By investigating a large geographic area, by extending the focus from lethal to sublethal thiamine deficiency, and by linking biochemical alterations to secondary effects, we demonstrate that the problem of thiamine deficiency is considerably more widespread and severe than previously reported.

  3. Widespread episodic thiamine deficiency in Northern Hemisphere wildlife

    Science.gov (United States)

    Balk, Lennart; Hägerroth, Per-Åke; Gustavsson, Hanna; Sigg, Lisa; Akerman, Gun; Ruiz Muñoz, Yolanda; Honeyfield, Dale C.; Tjarnlund, Ulla; Oliveira, Kenneth; Strom, Karin; McCormick, Stephen D.; Karlsson, Simon; Strom, Marika; van Manen, Mathijs; Berg, Anna-Lena; Halldórsson, Halldór P.; Stromquist, Jennie; Collier, Tracy K.; Borjeson, Hans; Morner, Torsten; Hansson, Tomas

    2016-01-01

    Many wildlife populations are declining at rates higher than can be explained by known threats to biodiversity. Recently, thiamine (vitamin B1) deficiency has emerged as a possible contributing cause. Here, thiamine status was systematically investigated in three animal classes: bivalves, ray-finned fishes, and birds. Thiamine diphosphate is required as a cofactor in at least five life-sustaining enzymes that are required for basic cellular metabolism. Analysis of different phosphorylated forms of thiamine, as well as of activities and amount of holoenzyme and apoenzyme forms of thiamine-dependent enzymes, revealed episodically occurring thiamine deficiency in all three animal classes. These biochemical effects were also linked to secondary effects on growth, condition, liver size, blood chemistry and composition, histopathology, swimming behaviour and endurance, parasite infestation, and reproduction. It is unlikely that the thiamine deficiency is caused by impaired phosphorylation within the cells. Rather, the results point towards insufficient amounts of thiamine in the food. By investigating a large geographic area, by extending the focus from lethal to sublethal thiamine deficiency, and by linking biochemical alterations to secondary effects, we demonstrate that the problem of thiamine deficiency is considerably more widespread and severe than previously reported.

  4. Leptin deficiency: clinical implications and opportunities for therapeutic interventions.

    Science.gov (United States)

    Blüher, Susan; Shah, Sunali; Mantzoros, Christos S

    2009-10-01

    The discovery of leptin has significantly advanced our understanding of the metabolic importance of adipose tissue and has revealed that both leptin deficiency and leptin excess are associated with severe metabolic, endocrine, and immunological consequences. We and others have shown that a prominent role of leptin in humans is to mediate the neuroendocrine adaptation to energy deprivation. Humans with genetic mutations in the leptin and leptin receptor genes have deregulated food intake and energy expenditure leading to a morbidly obese phenotype and a disrupted regulation in neuroendocrine and immune function and in glucose and fat metabolism. Observational and interventional studies in humans with (complete) congenital leptin deficiency caused by mutations in the leptin gene or with relative leptin deficiency as seen in states of negative energy balance such as lipoatrophy, anorexia nervosa, or exercise-induced hypothalamic and neuroendocrine dysfunction have contributed to the elucidation of the pathophysiological role of leptin in these conditions and of the clinical significance of leptin administration in these subjects. More specifically, interventional studies have demonstrated that several neuroendocrine, metabolic, or immune disturbances in these states could be restored by leptin administration. Leptin replacement therapy is currently available through a compassionate use program for congenital complete leptin deficiency and under an expanded access program to subjects with leptin deficiency associated with congenital or acquired lipoatrophy. In addition, leptin remains a potentially forthcoming treatment for several other states of energy deprivation including anorexia nervosa or milder forms of hypothalamic amenorrhea pending appropriate clinical trials.

  5. Genetics Home Reference: arginase deficiency

    Science.gov (United States)

    ... belongs to a class of genetic diseases called urea cycle disorders. The urea cycle is a sequence of reactions ... links) Baby's First Test GeneReview: Arginase Deficiency GeneReview: Urea Cycle Disorders Overview MedlinePlus Encyclopedia: Hereditary urea cycle abnormality National ...

  6. [Constitutional mismatch repair deficiency syndrome

    NARCIS (Netherlands)

    Jongmans, M.C.J.; Gidding, C.E.M.; Loeffen, J.; Wesseling, P.; Mensenkamp, A.; Hoogerbrugge, N.

    2015-01-01

    BACKGROUND: Constitutional mismatch repair deficiency (CMMR-D) syndrome is characterised by a significantly increased risk for developing cancer in childhood. It arises when both parents have a mutation in the same mismatch repair gene and pass it on to their child. CASE DESCRIPTION: An 8-year-old

  7. Carnitine palmityl transferase I deficiency

    NARCIS (Netherlands)

    Al-Aqeel, A. I.; Rashed, M. S.; Ruiter, J. P.; Al-Husseini, H. F.; Al-Amoudi, M. S.; Wanders, R. J.

    2001-01-01

    Carnitine palmityl transferase I is the key enzyme in the carnitine dependent transport of long chain fatty acids across the mitochondrial inner membrane and its deficiency results in a decrease rate of fatty acids beta-oxidation with decreased energy production. We reported a family of 3 affected

  8. Epigenetic Deficiencies and Replicative Stress

    DEFF Research Database (Denmark)

    Shoaib, Muhammad; Sørensen, Claus Storgaard

    2015-01-01

    Cancer cell-specific synthetic lethal interactions entail promising therapeutic possibilities. In this issue of Cancer Cell, Pfister et al. describe a synthetic lethal interaction where cancer cells deficient in H3K36me3 owing to SETD2 loss-of-function mutation are strongly sensitized to inhibiti...

  9. Management of Iron Deficiency Anemia

    Science.gov (United States)

    Jimenez, Kristine; Kulnigg-Dabsch, Stefanie

    2015-01-01

    Anemia affects one-fourth of the world’s population, and iron deficiency is the predominant cause. Anemia is associated with chronic fatigue, impaired cognitive function, and diminished well-being. Patients with iron deficiency anemia of unknown etiology are frequently referred to a gastroenterologist because in the majority of cases the condition has a gastrointestinal origin. Proper management improves quality of life, alleviates the symptoms of iron deficiency, and reduces the need for blood transfusions. Treatment options include oral and intravenous iron therapy; however, the efficacy of oral iron is limited in certain gastrointestinal conditions, such as inflammatory bowel disease, celiac disease, and autoimmune gastritis. This article provides a critical summary of the diagnosis and treatment of iron deficiency anemia. In addition, it includes a management algorithm that can help the clinician determine which patients are in need of further gastrointestinal evaluation. This facilitates the identification and treatment of the underlying condition and avoids the unnecessary use of invasive methods and their associated risks. PMID:27099596

  10. Dopamine beta-hydroxylase deficiency

    Directory of Open Access Journals (Sweden)

    Senard Jean-Michel

    2006-03-01

    Full Text Available Abstract Dopamine beta-hydroxylase (DβH deficiency is a very rare form of primary autonomic failure characterized by a complete absence of noradrenaline and adrenaline in plasma together with increased dopamine plasma levels. The prevalence of DβH deficiency is unknown. Only a limited number of cases with this disease have been reported. DβH deficiency is mainly characterized by cardiovascular disorders and severe orthostatic hypotension. First symptoms often start during a complicated perinatal period with hypotension, muscle hypotonia, hypothermia and hypoglycemia. Children with DβH deficiency exhibit reduced ability to exercise because of blood pressure inadaptation with exertion and syncope. Symptoms usually worsen progressively during late adolescence and early adulthood with severe orthostatic hypotension, eyelid ptosis, nasal stuffiness and sexual disorders. Limitation in standing tolerance, limited ability to exercise and traumatic morbidity related to falls and syncope may represent later evolution. The syndrome is caused by heterogeneous molecular alterations of the DBH gene and is inherited in an autosomal recessive manner. Restoration of plasma noradrenaline to the normal range can be achieved by therapy with the synthetic precursor of noradrenaline, L-threo-dihydroxyphenylserine (DOPS. Oral administration of 100 to 500 mg DOPS, twice or three times daily, increases blood pressure and reverses the orthostatic intolerance.

  11. [Osteomalacia and vitamin D deficiency].

    Science.gov (United States)

    Rader, C P; Corsten, N; Rolf, O

    2015-09-01

    Vitamin D and calcium deficiency has a higher incidence in the orthopedic-trauma surgery patient population than generally supposed. In the long term this can result in osteomalacia, a form of altered bone mineralization in adults, in which the cartilaginous, non-calcified osteoid does not mature to hard bone. The current value of vitamin D and its importance for bones and other body cells are demonstrated. The causes of vitamin D deficiency are insufficient sunlight exposure, a lack of vitamin D3 and calcium, malabsorption, and rare alterations of VDR signaling and phosphate metabolism. The main symptoms are bone pain, fatigue fractures, muscular cramps, muscle pain, and gait disorders, with an increased incidence of falls in the elderly. Osteopathies induced by pharmaceuticals, tumors, rheumatism or osteoporosis have to be considered as the main differential diagnoses. In addition to the recording of symptoms and medical imaging, the diagnosis of osteomalacia should be ensured by laboratory parameters. Adequate treatment consists of the high-dose intake of vitamin D3 and the replacement of phosphate if deficient. Vitamin D is one of the important hormone-like vitamins and is required in all human cells. Deficiency of vitamin D has far-reaching consequences not only for bone, but also for other organ systems.

  12. Genetics Home Reference: dihydropyrimidine dehydrogenase deficiency

    Science.gov (United States)

    ... 5-fluorouracil and capecitabine. These drugs are not broken down efficiently by people with dihydropyrimidine dehydrogenase deficiency ... of this enzyme. Because fluoropyrimidine drugs are also broken down by the dihydropyrimidine dehydrogenase enzyme, deficiency of ...

  13. Genetics Home Reference: 21-hydroxylase deficiency

    Science.gov (United States)

    ... adrenal hyperplasias that impair hormone production and disrupt sexual development. 21-hydroxylase deficiency is responsible for about 95 ... excess production of androgens leads to abnormalities of sexual development in people with 21-hydroxylase deficiency . A lack ...

  14. Genetics Home Reference: complement component 2 deficiency

    Science.gov (United States)

    ... Topic: Immune System and Disorders Health Topic: Lupus Genetic and Rare Diseases Information Center (1 link) Complement component 2 deficiency Additional NIH Resources (1 link) National Institute of Allergy and Infectious Diseases: Primary Immune Deficiency Diseases Educational Resources (6 ...

  15. Galactose Epimerase Deficiency: Expanding the Phenotype

    NARCIS (Netherlands)

    Dias Costa, Filipa; Ferdinandusse, Sacha; Pinto, Carla; Dias, Andrea; Keldermans, Liesbeth; Quelhas, Dulce; Matthijs, Gert; Mooijer, Petra A.; Diogo, Luísa; Jaeken, Jaak; Garcia, Paula

    2017-01-01

    Galactose epimerase deficiency is an inborn error of metabolism due to uridine diphosphate-galactose-4'-epimerase (GALE) deficiency. We report the clinical presentation, genetic and biochemical studies in two siblings with generalized GALE deficiency.Patient 1: The first child was born with a

  16. Common micronutrient deficiencies among food aid beneficiaries ...

    African Journals Online (AJOL)

    Results: Vitamin A and iron deficiencies were the most prevalent micronutrient deficiencies among food aid beneficiaries. Other probable deficiencies prevailing were zinc, vitamins thiamine, riboflavin, niacin folate, cyano-cobalamine, ascorbic acid vitamin D and calcium because of the low intake of dairy products and meat.

  17. Leptin Deficiency: Clinical Implications and Opportunities for Therapeutic Interventions

    OpenAIRE

    Bl?her, Susan; Shah, Sunali; Mantzoros, Christos S.

    2009-01-01

    The discovery of leptin has significantly advanced our understanding of the metabolic importance of adipose tissue and has revealed that both leptin deficiency and leptin excess are associated with severe metabolic, endocrine, and immunological consequences. We and others have shown that a prominent role of leptin in humans is to mediate the neuroendocrine adaptation to energy deprivation. Humans with genetic mutations in the leptin and leptin receptor genes have deregulated food intake and e...

  18. Cobalt-deficiency-induced hyperhomocysteinaemia and oxidative status of cattle.

    Science.gov (United States)

    Stangl, G I; Schwarz, F J; Jahn, B; Kirchgessner, M

    2000-01-01

    In ruminants, Co is required for the synthesis of vitamin B12, which in turn is needed for the resynthesis of methionine by methylation of homocysteine and thus, cobalamin deficiency may induce hyperhomocysteinaemia which is brought into context with perturbations of the antioxidative-prooxidative balance. The present study was conducted to explore whether Co deficiency in cattle is also associated with homocysteine-induced disturbances of oxidative status. Co deficiency was induced in cattle by feeding two groups of animals on either a basal maize-silage-based diet that was moderately low in Co (83 micrograms Co/kg DM), or the same diet supplemented with Co to a total of 200 micrograms Co/kg DM, for 43 weeks. Co deficiency was apparent from a reduced vitamin B12 status in serum and liver and an accumulation of homocysteine in plasma which was in excess of 4.8 times higher in Co-deprived cattle than in controls. The much increased level of circulating homocysteine did not indicate severe disturbances in antioxidant-prooxidant balance as measured by individual markers of lipid peroxidation, protein oxidation, and the antioxidative defence system. There were no quantitative difference in plasma thiol groups, nor were there significant changes in concentrations of alpha-tocopherol, microsomal thiobarbituric acid-reactive substances and carbonyl groups in liver. However, there was a trend toward increased plasma carbonyl levels indicating a slight degradation of plasma proteins in the hyperhomocysteinaemic cattle. Analysis of the hepatic catalase (EC 1.11.1.6) activity revealed an 11% reduction in Co-deficient cattle relative to the controls. These results indicate that long-term moderate Co deficiency may induce a severe accumulation of plasma homocysteine in cattle, but considerable abnormalities in oxidative status failed to appear.

  19. DNA repair deficiency in neurodegeneration

    DEFF Research Database (Denmark)

    Jeppesen, Dennis Kjølhede; Bohr, Vilhelm A; Stevnsner, Tinna V.

    2011-01-01

    Deficiency in repair of nuclear and mitochondrial DNA damage has been linked to several neurodegenerative disorders. Many recent experimental results indicate that the post-mitotic neurons are particularly prone to accumulation of unrepaired DNA lesions potentially leading to progressive...... neurodegeneration. Nucleotide excision repair is the cellular pathway responsible for removing helix-distorting DNA damage and deficiency in such repair is found in a number of diseases with neurodegenerative phenotypes, including Xeroderma Pigmentosum and Cockayne syndrome. The main pathway for repairing oxidative...... base lesions is base excision repair, and such repair is crucial for neurons given their high rates of oxygen metabolism. Mismatch repair corrects base mispairs generated during replication and evidence indicates that oxidative DNA damage can cause this pathway to expand trinucleotide repeats, thereby...

  20. Vitamin D deficiency in Fibromyalgia

    International Nuclear Information System (INIS)

    Bhatty, S.A.; Shaikh, N.A.; Irfan, M.; Kashif, S.M.; Vaswani, A.S.; Sumbhai, A.; Gunpat

    2010-01-01

    Objective: To check the Vitamin D levels in patients diagnosed as fibromyagia in our population. Methods: Study was done at Medical OPD of Civil Hospital Karachi, from January to March 2009. Female patients diagnosed as Fibromyalgia according to American College of Rheumatology (ACR) criteria and exclusion of systemic illness on examination, and normal reports of blood CP, ESR, serum calcium, phosphate and Alkaline Phosphatase, were asked to get Vitamin D levels in their serum. Vitamin D deficiency is defined as 30 ng/ml. Result: Forty female patients were included in the study. The mean age was 37.65 +- 11.5 years. Mean Vitamin D level was 17.41 +- 5.497 ng/ml. Thirty two (80%) of patients had Vitamin D deficiency, mean levels of 15.855 +- 4.918 ng/ml and 8(20%) had Vitamin D insufficiency, mean levels of 23.64 +- 2.39 ng/ml. Patients with vitamin D deficiency and age less than 45 years were 22 (68.75%), had mean vitamin D level 16.87 +- 4.48 ng/ml whereas in age ranging from 46-75 years were 10 (31.25%) had mean vitamin D level 16.09 +- 6.45 ng/ml. Conclusion: Vitamin D deficiency is frequently seen in patients diagnosed as fibromyalgia and nonspecific musculoskeletal pain in our population. Although the sample size of the study is small, but the figures are so alarming that it is an eye opener towards the need of a population based study, including normal population as well as those presenting with musculoskeletal pain. (author)

  1. Zinc Deficiency in Humans and its Amelioration

    OpenAIRE

    Yashbir Singh Shivay

    2015-01-01

    Zinc (Zn) deficiency in humans has recently received considerable attention. Global mortality in children under 5 years of age in 2004 due to Zn deficiency was estimated at 4,53,207 as against 6,66,771 for vitamin A deficiency; 20,854 for iron deficiency and 3,619 for iodine deficiency. In humans 2800-3000 proteins contain Zn prosthetic group and Zn is an integral component of zinc finger prints that regulate DNA transcription. Zinc is a Type-2 nutrient, which means that its concentration in ...

  2. Zinc deficiency in the pediatric age group is common but underevaluated.

    Science.gov (United States)

    Vuralli, Dogus; Tumer, Leyla; Hasanoglu, Alev

    2017-08-01

    Subclinical micronutrient deficiencies have been gradually becoming more important as a public health problem and drawing attention of the health authorities. Today it has been known that detecting and treating people having deficiency symptoms alone is no longer sufficient. It is important to detect and prevent any deficiency before it displays clinical manifestations. Zinc deficiency is one of the most widespread micronutrient deficiencies. In this study, we aimed to evaluate the zinc status and the associated factors in healthy school-age children. The study was carried out in schools in Altindag, the district of Ankara. A total of 1063 healthy children, 585 girls and 478 boys, aged 5-16 years were included in the study. Serum zinc, high-sensitivity C-reactive protein levels and white blood cell count were measured. A serum zinc level zinc deficiency for children zinc concentration were set at 66 μg/dL for females and 70 μg/dL for males. A questionnaire was developed to collect socioeconomic and demographic information of the participants. The prevalence of subclinical zinc deficiency in children attending the study was detected to be 27.8%. This high ratio showed zinc deficiency was an important health problem in the Altindag district of Ankara, Turkey. Evaluating the indicators of zinc deficiency such as serum zinc concentration, dietary zinc intake and stunting prevalence, this study is the most comprehensive epidemiological study performed in children in Turkey. This study reveals the high prevalence of subclinical zinc deficiency and indicates that zinc deficiency is a public health concern for the study population.

  3. Recombination-deficient mutants of Bacillus subtilis

    International Nuclear Information System (INIS)

    Sadaie, Y.; Kada, T.

    1976-01-01

    Two mutant strains of Bacillus subtilis Marburg, NIG43 and NIG45, were isolated. They showed high sensitivities to gamma rays, ultraviolet light (uv), and chemicals. Deficiencies in genetic recombination of these two mutants were shown by the experiments on their capacity in transformation, SPO2 transfection, and PBS1 phage transduction, as well as on their radiation and drug sensitivities and their Hcr + capacity for uv-exposed phage M2. Some of these characteristics were compared with those of the known strains possessing the recA1 or recB2 alleles. Mapping studies revealed that the mutation rec-43 of strain NIG43 lies in the region of chromosome replication origin. The order was purA dna-8132 rec-43. Another mutation, rec-45, of strain NIG45 was found to be tightly linked to recA1. The mutation rec-43 reduced mainly the frequency of PBS1 transduction. On the other hand, the mutation rec-45 reduced the frequency of recombination involved both in transformation and PBS1 tranduction. The mutation rec-43 of strain NIG43 is conditional, but rec-45 of strain NIG45 is not. The uv impairment in cellular survival of strain NIG43 was gradually reverted at higher salt or sucrose concentrations, suggesting cellular possession of a mutated gene product whose function is conditional. In contrast to several other recombination-deficient strains, SPO2 lysogens of strains NIG43 and NIG45 were not inducible, indicating involvement of rec-43 + or rec-45 + gene product in the development of SPO2 prophage to a vegetative form. The uv-induced deoxyribonucleic acid degradation in vegetative cells was higher in rec-43 and rec-45 strains

  4. Radiochemical studies of neutron deficient actinide isotopes

    International Nuclear Information System (INIS)

    Williams, K.E.

    1978-04-01

    The production of neutron deficient actinide isotopes in heavy ion reactions was studied using alpha, gamma, x-ray, and spontaneous fission detection systems. A new isotope of berkelium, 242 Bk, was produced with a cross-section of approximately 10 μb in reactions of boron on uranium and nitrogen on thorium. It decays by electron capture with a half-life of 7.0 +- 1.3 minutes. The alpha-branching ratio for this isotope is less than 1% and the spontaneous fission ratio is less than 0.03%. Studies of (Heavy Ion, pxn) and (Heavy Ion, αxn) transfer reactions in comparison with (Heavy ion, xn) compound nucleus reactions revealed transfer reaction cross-sections equal to or greater than the compound nucleus yields. The data show that in some cases the yield of an isotope produced via a (H.I.,pxn) or (H.I.,αxn) reaction may be higher than its production via an xn compound nucleus reaction. These results have dire consequences for proponents of the ''Z 1 + Z 2 = Z/sub 1+2/'' philosophy. It is no longer acceptable to assume that (H.I.,pxn) and (H.I.,αxn) product yields are of no consequence when studying compound nucleus reactions. No evidence for spontaneous fission decay of 228 Pu, 230 Pu, 232 Cm, or 238 Cf was observed indicating that strictly empirical extrapolations of spontaneous fission half-life data is inadequate for predictions of half-lives for unknown neutron deficient actinide isotopes

  5. Radiochemical studies of neutron deficient actinide isotopes

    Energy Technology Data Exchange (ETDEWEB)

    Williams, K.E.

    1978-04-01

    The production of neutron deficient actinide isotopes in heavy ion reactions was studied using alpha, gamma, x-ray, and spontaneous fission detection systems. A new isotope of berkelium, /sup 242/Bk, was produced with a cross-section of approximately 10 ..mu..b in reactions of boron on uranium and nitrogen on thorium. It decays by electron capture with a half-life of 7.0 +- 1.3 minutes. The alpha-branching ratio for this isotope is less than 1% and the spontaneous fission ratio is less than 0.03%. Studies of (Heavy Ion, pxn) and (Heavy Ion, ..cap alpha..xn) transfer reactions in comparison with (Heavy ion, xn) compound nucleus reactions revealed transfer reaction cross-sections equal to or greater than the compound nucleus yields. The data show that in some cases the yield of an isotope produced via a (H.I.,pxn) or (H.I.,..cap alpha..xn) reaction may be higher than its production via an xn compound nucleus reaction. These results have dire consequences for proponents of the ''Z/sub 1/ + Z/sub 2/ = Z/sub 1+2/'' philosophy. It is no longer acceptable to assume that (H.I.,pxn) and (H.I.,..cap alpha..xn) product yields are of no consequence when studying compound nucleus reactions. No evidence for spontaneous fission decay of /sup 228/Pu, /sup 230/Pu, /sup 232/Cm, or /sup 238/Cf was observed indicating that strictly empirical extrapolations of spontaneous fission half-life data is inadequate for predictions of half-lives for unknown neutron deficient actinide isotopes.

  6. Primary Carnitine (OCTN2) Deficiency Without Neonatal Carnitine Deficiency

    OpenAIRE

    de Boer, L.; Kluijtmans, L. A. J.; Morava, E.

    2012-01-01

    Although the diagnosis of a primary carnitine deficiency is usually based on a very low level of free and total carnitine (free carnitine: 1–5 μM, normal 20–55 μM) (Longo et al. 2006), we detected a patient via newborn screening with a total carnitine level 67 % of the normal value. At the age of 1 year, after interruption of carnitine supplementation for a 4-week period the carnitine profile was assessed and the free carnitine level had dropped to 10.4 μmol/l (normal: 20–55 μM) and total car...

  7. A Case With Short Stature, Growth Hormone Deficiency and 46, XX, Xq27-qter Deletion.

    Science.gov (United States)

    Yıldırım, Şule; Topaloğlu, Naci; Tekin, Mustafa; Sılan, Fatma

    2017-10-01

    We report a case of 11-year-old girl with growth retardation and 46, XX, Xq27-qter deletion. The endocrinologic evaluation revealed growth hormone deficiency. In karyotype analysis  46, XX, Xq27-qter deletion was determined. The deletion of terminal region of chromosome 27 is most commonly being detected during the evaluation of infertility, premature ovarian insufficiency or in screening for fragile X carrier status. To our knowledge, this is the first reported case with 46, XX, Xq27-qter deletion and growth hormone deficiency. Furthermore, this case might facilitate future search for candidate genes involved in growth hormone deficiency.

  8. Selected systems engineering process deficiencies and their consequences

    Science.gov (United States)

    Thomas, L. Dale

    2007-06-01

    The systems engineering process is well established and well understood. While this statement could be argued in the light of the many systems engineering guidelines and that have been developed, comparative review of these respective descriptions reveal that they differ primarily in the number of discrete steps or other nuances, and are at their core essentially common. Likewise, the systems engineering textbooks differ primarily in the context for application of systems engineering or in the utilization of evolved tools and techniques, not in the basic method. Thus, failures in systems engineering cannot credibly be attributed to implementation of the wrong systems engineering process among alternatives. However, numerous system failures can be attributed to deficient implementation of the systems engineering process. What may clearly be perceived as a systems engineering deficiency in retrospect can appear to be a well considered system engineering efficiency in real time—an efficiency taken to reduce cost or meet a schedule, or more often both. Typically these efficiencies are grounded on apparently solid rationale, such as reuse of heritage hardware or software. Over time, unintended consequences of a systems engineering process deficiency may begin to be realized, and unfortunately often the consequence is systems failure. This paper describes several actual cases of system failures that resulted from deficiencies in their systems engineering process implementation, including the Ariane 5 and the Hubble Space Telescope.

  9. No changes in heme synthesis in human Friedreich´s ataxia erythroid progenitor cells.

    Science.gov (United States)

    Steinkellner, Hannes; Singh, Himanshu Narayan; Muckenthaler, Martina U; Goldenberg, Hans; Moganty, Rajeswari R; Scheiber-Mojdehkar, Barbara; Sturm, Brigitte

    2017-07-20

    Friedreich's ataxia (FRDA) is a neurodegenerative disease caused by reduced expression of the protein frataxin. Frataxin is thought to play a role in iron-sulfur cluster biogenesis and heme synthesis. In this study, we used erythroid progenitor stem cells obtained from FRDA patients and healthy donors to investigate the putative role, if any, of frataxin deficiency in heme synthesis. We used electrochemiluminescence and qRT-PCR for frataxin protein and mRNA quantification. We used atomic absorption spectrophotometry for iron levels and a photometric assay for hemoglobin levels. Protoporphyrin IX and Ferrochelatase were analyzed using auto-fluorescence. An "IronChip" microarray analysis followed by a protein-protein interaction analysis was performed. FRDA patient cells showed no significant changes in iron levels, hemoglobin synthesis, protoporphyrin IX levels, and ferrochelatase activity. Microarray analysis presented 11 genes that were significantly changed in all patients compared to controls. The genes are especially involved in oxidative stress, iron homeostasis and angiogenesis. The mystery about the involvement of frataxin on iron metabolism raises the question why frataxin deficiency in primary FRDA cells did not lead to changes in biochemical parameters of heme synthesis. It seems that alternative pathways can circumvent the impact of frataxin deficiency on heme synthesis. We show for the first time in primary FRDA patient cells that reduced frataxin levels are still sufficient for heme synthesis and possibly other mechanisms can overcome reduced frataxin levels in this process. Our data strongly support the fact that so far no anemia in FRDA patients was reported. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Use of radionuclides in the study of iron metabolism in iron deficient states

    International Nuclear Information System (INIS)

    Anatkov, A.; Karakostov, K.; Iliev, Z.; Dimitrov, L.

    1977-01-01

    A study of erythropoiesis in iron deficient anemias by simultaneous labelling with the radionuclides iron 59 and chromium 51 revealed accelerated iron circuit, higher percentage of daily hemolysis, severely reduced or even absent labile reserves, decreased volume of packed red cells with no decrease of blood volume. Adequate iron 59 utilization was observed after administration of large doses of iron (500 mg) in the treatment of iron deficient anemias. (author)

  11. Skin wound healing in MMP2-deficient and MMP2 / plasminogen double-deficient mice

    DEFF Research Database (Denmark)

    Frøssing, Signe; Rønø, Birgitte; Hald, Andreas

    2010-01-01

    -sensitive MMPs during wound healing. To address whether MMP2 is accountable for the galardin-induced healing deficiency in wildtype and Plg-deficient mice, incisional skin wounds were generated in MMP2 single-deficient mice and in MMP2/Plg double-deficient mice and followed until healed. Alternatively, tissue...... was isolated 7 days post wounding for histological and biochemical analyses. No difference was found in the time from wounding to overt gross restoration of the epidermal surface between MMP2-deficient and wildtype control littermate mice. MMP2/Plg double-deficient mice were viable and fertile, and displayed...... an unchallenged general phenotype resembling that of Plg-deficient mice, including development of rectal prolapses. MMP2/Plg double-deficient mice displayed a slight increase in the wound length throughout the healing period compared with Plg-deficient mice. However, the overall time to complete healing...

  12. Toward reassessing data-deficient species.

    Science.gov (United States)

    Bland, Lucie M; Bielby, Jon; Kearney, Stephen; Orme, C David L; Watson, James E M; Collen, Ben

    2017-06-01

    One in 6 species (13,465 species) on the International Union for Conservation of Nature (IUCN) Red List is classified as data deficient due to lack of information on their taxonomy, population status, or impact of threats. Despite the chance that many are at high risk of extinction, data-deficient species are typically excluded from global and local conservation priorities, as well as funding schemes. The number of data-deficient species will greatly increase as the IUCN Red List becomes more inclusive of poorly known and speciose groups. A strategic approach is urgently needed to enhance the conservation value of data-deficient assessments. To develop this, we reviewed 2879 data-deficient assessments in 6 animal groups and identified 8 main justifications for assigning data-deficient status (type series, few records, old records, uncertain provenance, uncertain population status or distribution, uncertain threats, taxonomic uncertainty, and new species). Assigning a consistent set of justification tags (i.e., consistent assignment to assessment justifications) to species classified as data deficient is a simple way to achieve more strategic assessments. Such tags would clarify the causes of data deficiency; facilitate the prediction of extinction risk; facilitate comparisons of data deficiency among taxonomic groups; and help prioritize species for reassessment. With renewed efforts, it could be straightforward to prevent thousands of data-deficient species slipping unnoticed toward extinction. © 2016 Society for Conservation Biology.

  13. Vitamin D deficiency in Europe

    DEFF Research Database (Denmark)

    Cashman, Kevin D.; Dowling, Kirsten G; Škrabáková, Zuzana

    2016-01-01

    25(OH)D values from national health/nutrition surveys. OBJECTIVE: This study applied VDSP protocols to serum 25(OH)D data from representative childhood/teenage and adult/older adult European populations, representing a sizable geographical footprint, to better quantify the prevalence of vitamin D...... is evident throughout the European population at prevalence rates that are concerning and that require action from a public health perspective. What direction these strategies take will depend on European policy but should aim to ensure vitamin D intakes that are protective against vitamin D deficiency...

  14. Zinc or copper deficiency-induced impaired inflammatory response to brain trauma may be caused by the concomitant metallothionein changes

    DEFF Research Database (Denmark)

    Penkowa, Milena; Giralt, M.; Thomsen, Pernille Sjølin

    2001-01-01

    , and this response was significantly blunted by zinc deficiency. The MT-III isoform was moderately increased by both TBI and zinc deficiency. TBI strongly increased oxidative stress levels, as demonstrated by malondialdehyde (MDA), protein tyrosine nitration (NITT), and nuclear factor kappaB (NF-kappaB) levels irs......, all of which were potentiated by zinc deficiency. Further analysis revealed unbalanced expression of prooxidant and antioxidant proteins besides MT, since the levels of inducible nitric oxide synthase (iNOS) and Cu,Zn-SOD were increased and decreased, respectively, by zinc deficiency. All......The role of zinc- and copper-deficient diets on the inflammatory response to traumatic brain injury (TBI) has been evaluated in adult rats. As expected, zinc deficiency decreased food intake and body weight gain, and the latter effect was higher than that observed in pair-fed rats. In noninjured...

  15. White centered retinal hemorrhages in vitamin b(12) deficiency anemia.

    Science.gov (United States)

    Zehetner, Claus; Bechrakis, Nikolaos E

    2011-05-01

    To report a case of severe vitamin B(12) deficiency anemia presenting with white centered retinal hemorrhages. Interventional case report. A 40-year-old man, general practitioner himself, presented with a 1-day history of diminished left visual acuity and a drop-shaped central scotoma. The corrected visual acuities were 20/20, OD and 20/100, OS. Ophthalmic examination revealed bilaterally pale tarsal conjunctiva, discretely icteric bulbar conjunctiva and disseminated white centered intraretinal hemorrhages with foveal involvement. OCT imaging through these lesions revealed a retinal thickening caused by a sub-ILM accumulation of hyperreflective and inhomogeneous deposits within the nerve fiber layer. Immediate laboratory work-up showed severe megaloblastic anemia caused by vitamin B(12) deficiency requiring erythrocyte transfusions. Most reports of white centered retinal hemorrhages have been described in patients with leukemic retinopathy and bacterial endocarditis. It is interesting that this case of vitamin B(12) deficiency anemia retinopathy has a clinically indistinguishable fundus appearance. This is probably due to the common pathology of capillary disruption and subsequent hemostatic fibrin plug formation. In megaloblastic anemia, direct anoxia results in endothelial dysfunction. The loss of impermeability allows extrusion of whole blood and subsequent diffusion from the disrupted site throughout and above the nerve fiber layer. Therefore the biomicroscopic pattern of white centered hemorrhages observed in anemic retinopathy is most likely due to the clot formation as the reparative sequence after capillary rupture.

  16. White Centered Retinal Hemorrhages in Vitamin B12 Deficiency Anemia

    Directory of Open Access Journals (Sweden)

    Claus Zehetner

    2011-05-01

    Full Text Available Background: To report a case of severe vitamin B12 deficiency anemia presenting with white centered retinal hemorrhages. Methods: Interventional case report. Results: A 40-year-old man, general practitioner himself, presented with a 1-day history of diminished left visual acuity and a drop-shaped central scotoma. The corrected visual acuities were 20/20, OD and 20/100, OS. Ophthalmic examination revealed bilaterally pale tarsal conjunctiva, discretely icteric bulbar conjunctiva and disseminated white centered intraretinal hemorrhages with foveal involvement. OCT imaging through these lesions revealed a retinal thickening caused by a sub-ILM accumulation of hyperreflective and inhomogeneous deposits within the nerve fiber layer. Immediate laboratory work-up showed severe megaloblastic anemia caused by vitamin B12 deficiency requiring erythrocyte transfusions. Discussion: Most reports of white centered retinal hemorrhages have been described in patients with leukemic retinopathy and bacterial endocarditis. It is interesting that this case of vitamin B12 deficiency anemia retinopathy has a clinically indistinguishable fundus appearance. This is probably due to the common pathology of capillary disruption and subsequent hemostatic fibrin plug formation. In megaloblastic anemia, direct anoxia results in endothelial dysfunction. The loss of impermeability allows extrusion of whole blood and subsequent diffusion from the disrupted site throughout and above the nerve fiber layer. Therefore the biomicroscopic pattern of white centered hemorrhages observed in anemic retinopathy is most likely due to the clot formation as the reparative sequence after capillary rupture.

  17. Micronutrient deficiency in urban Indonesia.

    Science.gov (United States)

    Gross, R; Schultink, W

    1997-06-01

    The economic situation of Indonesia is characterized by a large increase in the gross national product which has been on average 7% annually during the last ten years. This was accompanied by rapid urbanization. With the economic improvement, "First World" and "Third World" health and nutrition problems are coexisting in Indonesia. In 1992, the most common of death cause was cardiovascular disease whereas tuberculosis was the second ranking. About 40% of the preschool children are stunted. The main stable food and energy source is rice, although the urban population has a more diverse food pattern than the rural population. In Jakarta, many children receive too late colostrum feeding and mothers are not aware about the importance of correct breastfeeding practices after delivery. Three studies had shown that about one fifth of preschool children and one fourth of elderly take micronutrient supplements. Nevertheless, micronutrient deficiencies are prevalent in Jakarta. About one third of women suffer from moderate vitamin A deficiency (plasma retinol middle class to spend more time and money to solve their own problems.

  18. Jasmonate signaling is activated in the very early stages of iron deficiency responses in rice roots.

    Science.gov (United States)

    Kobayashi, Takanori; Itai, Reiko Nakanishi; Senoura, Takeshi; Oikawa, Takaya; Ishimaru, Yasuhiro; Ueda, Minoru; Nakanishi, Hiromi; Nishizawa, Naoko K

    2016-07-01

    Under low iron availability, plants induce the expression of various genes involved in iron uptake and translocation at the transcriptional level. This iron deficiency response is affected by various plant hormones, but the roles of jasmonates in this response are not well-known. We investigated the involvement of jasmonates in rice iron deficiency responses. High rates of jasmonate-inducible genes were induced during the very early stages of iron deficiency treatment in rice roots. Many jasmonate-inducible genes were also negatively regulated by the ubiquitin ligases OsHRZ1 and OsHRZ2 and positively regulated by the transcription factor IDEF1. Ten out of 35 genes involved in jasmonate biosynthesis and signaling were rapidly induced at 3 h of iron deficiency treatment, and this induction preceded that of known iron deficiency-inducible genes involved in iron uptake and translocation. Twelve genes involved in jasmonate biosynthesis and signaling were also upregulated in HRZ-knockdown roots. Endogenous concentrations of jasmonic acid and jasmonoyl isoleucine tended to be rapidly increased in roots in response to iron deficiency treatment, whereas these concentrations were higher in HRZ-knockdown roots under iron-sufficient conditions. Analysis of the jasmonate-deficient cpm2 mutant revealed that jasmonates repress the expression of many iron deficiency-inducible genes involved in iron uptake and translocation under iron sufficiency, but this repression is partly canceled under an early stage of iron deficiency. These results indicate that jasmonate signaling is activated during the very early stages of iron deficiency, which is partly regulated by IDEF1 and OsHRZs.

  19. Dysfunctional TCA-Cycle Metabolism in Glutamate Dehydrogenase Deficient Astrocytes

    DEFF Research Database (Denmark)

    Nissen, Jakob D; Pajęcka, Kamilla; Stridh, Malin H

    2015-01-01

    aminotransferase (AAT) catalyze the reversible reaction between glutamate and α-ketoglutarate, which is the initial step for glutamate to enter TCA cycle metabolism. In contrast to GDH, AAT requires a concomitant interconversion of oxaloacetate and aspartate. We have investigated the role of GDH in astrocyte...... Labeling of aspartate and TCA cycle intermediates confirmed that the increased amount of aspartate is associated with elevated TCA cycle flux from α-ketoglutarate to oxaloacetate, i.e. truncated TCA cycle. (13) C Glucose metabolism was elevated in GDH deficient astrocytes as observed by increased de novo...... synthesis of aspartate via pyruvate carboxylation. In the absence of glucose, lactate production from glutamate via malic enzyme was lower in GDH deficient astrocytes. In conclusions, our studies reveal that metabolism via GDH serves an important anaplerotic role by adding net carbon to the TCA cycle...

  20. Folic acid deficiency optic neuropathy: A case report

    Directory of Open Access Journals (Sweden)

    de Silva Punyanganie

    2008-09-01

    Full Text Available Abstract Introduction Nutritional optic neuropathies are uncommon and can be associated with gradual visual loss and optic atrophy or sudden vision loss and optic disc swelling. Case presentation A 44-year-old woman presented with a 4-week history of progressive visual loss and was noted to have bilateral retrobulbar optic neuropathy. No other clinical abnormality was noted. Investigations revealed severe folate deficiency with normal vitamin B12 levels. Her alcohol and tobacco consumption was moderate and subsequent correction of folate levels with oral supplementation has led to improvement in her visual acuity. Conclusion This case highlights an unusual presentation of folic acid deficiency that may present to the general physician.

  1. New insights into iron deficiency and iron deficiency anemia.

    Science.gov (United States)

    Camaschella, Clara

    2017-07-01

    Recent advances in iron metabolism have stimulated new interest in iron deficiency (ID) and its anemia (IDA), common conditions worldwide. Absolute ID/IDA, i.e. the decrease of total body iron, is easily diagnosed based on decreased levels of serum ferritin and transferrin saturation. Relative lack of iron in specific organs/tissues, and IDA in the context of inflammatory disorders, are diagnosed based on arbitrary cut offs of ferritin and transferrin saturation and/or marker combination (as the soluble transferrin receptor/ferritin index) in an appropriate clinical context. Most ID patients are candidate to traditional treatment with oral iron salts, while high hepcidin levels block their absorption in inflammatory disorders. New iron preparations and new treatment modalities are available: high-dose intravenous iron compounds are becoming popular and indications to their use are increasing, although long-term side effects remain to be evaluated. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Genetics Home Reference: isolated growth hormone deficiency

    Science.gov (United States)

    ... can be inherited? More about Inheriting Genetic Conditions Diagnosis & Management Resources Genetic Testing (4 links) Genetic Testing Registry: Ateleiotic dwarfism Genetic Testing Registry: Autosomal dominant isolated somatotropin deficiency ...

  3. Vitamin C deficiency in weanling guinea pigs

    DEFF Research Database (Denmark)

    Lykkesfeldt, Jens; Trueba, Gilberto Perez; Poulsen, Henrik E.

    2007-01-01

    Neonates are particularly susceptible to malnutrition due to their limited reserves of micronutrients and their rapid growth. In the present study, we examined the effect of vitamin C deficiency on markers of oxidative stress in plasma, liver and brain of weanling guinea pigs. Vitamin C deficiency...... increased, while protein oxidation decreased (P¼0003). The results show that the selective preservation of brain ascorbate and induction of DNA repair in vitamin C-deficient weanling guinea pigs is not sufficient to prevent oxidative damage. Vitamin C deficiency may therefore be particularly adverse during...

  4. Development of additional pituitary hormone deficiencies in pediatric patients originally diagnosed with idiopathic isolated GH deficiency

    NARCIS (Netherlands)

    W.F. Blum (Werner); C.L. Deal (Cheri Lynn); A.G. Zimmermann (Alan); E.P. Shavrikova (Elena); C.J. Child (Christopher); C.A. Quigley (Charmian); S.L.S. Drop (Stenvert); G. Cutler (Gordon); R.G. Rosenfeld (Ron)

    2014-01-01

    textabstractObjective: We assessed the characteristics of children initially diagnosed with idiopathic isolated GH deficiency (IGHD) who later developed additional (multiple) pituitary hormone deficiencies (MPHD). Design: Data were analyzed for 5805 pediatric patients with idiopathic IGHD, who were

  5. Iodine deficiency disorders in Sarawak, Malaysia.

    Science.gov (United States)

    Kiyu, A; Tambi, Z; Ahmad, Y

    1998-12-01

    The state of Sarawak in Malaysia has a high prevalence of iodine deficiency disorders (IDD). This has been revealed through a review of goitre surveys that were carried out in the State from the early 1970s to the 1990s. The primary cause was low iodine intake. Contributory factors were low iodine content in the soil and water as well as high cassava consumption. Virtual elimination of IDD is one of the nutritional goals of the IDD prevention and control programs. The strategies adopted include the iodination of coarse salt, which is sold in the market by shopkeepers and also provided free from government health clinics; legislation requiring that salt sold in IDD-gazetted areas must be iodised; and the use of iodinators to iodise water supplied by the gravity-feed system to villages and boarding schools in rural areas. The indicators used in the monitoring and evaluation of the program include the availability of iodised salt in the market and households, iodine levels in water supply that had been fitted with iodinators, goitre volume measured by ultrasound, and urinary iodine excretion among school children.

  6. Immunoglobulin class-switch recombination deficiencies.

    Science.gov (United States)

    Durandy, Anne; Kracker, Sven

    2012-07-30

    Immunoglobulin class-switch recombination deficiencies (Ig-CSR-Ds) are rare primary immunodeficiencies characterized by defective switched isotype (IgG/IgA/IgE) production. Depending on the molecular defect in question, the Ig-CSR-D may be combined with an impairment in somatic hypermutation (SHM). Some of the mechanisms underlying Ig-CSR and SHM have been described by studying natural mutants in humans. This approach has revealed that T cell-B cell interaction (resulting in CD40-mediated signaling), intrinsic B-cell mechanisms (activation-induced cytidine deaminase-induced DNA damage), and complex DNA repair machineries (including uracil-N-glycosylase and mismatch repair pathways) are all involved in class-switch recombination and SHM. However, several of the mechanisms required for full antibody maturation have yet to be defined. Elucidation of the molecular defects underlying the diverse set of Ig-CSR-Ds is essential for understanding Ig diversification and has prompted better definition of the clinical spectrum of diseases and the development of increasingly accurate diagnostic and therapeutic approaches.

  7. A case report: Familial glucocorticoid deficiency associated with familial focal segmental glomerulosclerosis

    Directory of Open Access Journals (Sweden)

    Ram Nanik

    2012-12-01

    Full Text Available Abstract Background Familial glucocorticoid deficiency (FGD is a rare autosomal recessive disorder characterized by isolated glucocorticoid deficiency in the presence of normal plasma renin and aldosterone level. Focal segmental glomerulosclerosis (FSGS is a form of glomerular disease associated with proteinuria and nephritic syndrome. This is the first case of familial glucocorticoid deficiency associated with familial focal segmental glomerulosclerosis. Case presentation An eight month old boy presented with increased genital pigmentation. Initial investigation revealed that he was glucocorticoid deficient and was started on hydrocortisone and fludrocortisone with a diagnosis of primary adrenal insufficiency. Later fludrocortisone was withdrawn and he was diagnosed to have isolated glucocorticoid deficiency. He later developed focal segmental glomerulosclerosis for which he underwent renal transplantation at the age of five years. Now at the age of twelve years, this boy is doing well on hydrocortisone treatment. His two siblings and a first degree cousin also had isolated glucocorticoid deficiency. One of the above two siblings died due to renal failure secondary to focal segmental glomerulosclerosis. Conclusion Patients with familial glucocorticoid deficiency should be carefully followed for development of features of nephrotic syndrome.

  8. Present status of understanding on the G6PD deficiency and natural selection

    Directory of Open Access Journals (Sweden)

    Tripathy V

    2007-01-01

    Full Text Available G6PD deficiency is a common hemolytic genetic disorder, particularly in the areas endemic to malaria. Individuals are generally asymptomatic and hemolytic anemia occurs when some anti-malarial drugs or other oxidizing chemicals are administered. It has been proposed that G6PD deficiency provides protection against malaria. Maintaining of G6PD deficient alleles at polymorphic proportions is complicated because of the X-linked nature of G6PD deficiency. A comprehensive review of the literature on the hypothesis of malarial protection and the nature of the selection is being presented. Most of the epidemiological, in vitro and in vivo studies report selection for G6PD deficiency. Analysis of the G6PD gene also reveals that G6PD-deficient alleles show some signatures of selection. However, the question of how this polymorphism is being maintained remains unresolved because the selection/fitness coefficients for the different genotypes in the two sexes have not been established. Prevalence of G6PD deficiency in Indian caste and tribal populations and the different variants reported has also been reviewed.

  9. Automated deficiency letter data base

    International Nuclear Information System (INIS)

    Jones, R.D.

    1983-12-01

    An automated data base relevant to the various licensee deficiencies that accrue during the materials licensing application review process of the Nuclear Regulatory Commission (NRC) is described. A data base management system (DBMs) is used for data retrieval, file-tending, and examination of the interrelationships among the data types in the data base. Use of word processors to emulate computer terminals for the purpose of data base population (loading) and report generation is discussed. Also described is the technique used to link, for update purposes, the data base (accessed by means of SYSTEM 2000 on a CDC 6600 computer) to the NRC Material License Master File resident on the National Institutes of Health (NIH) IBM System 370 computer. A user's manual that provides easy-to-understand instructions for the nonprogramming user on how to generate ad hoc analytical reports to facilitate management decisions is also included

  10. [Constitutional mismatch repair deficiency syndrome].

    Science.gov (United States)

    Jongmans, Marjolijn C; Gidding, Corrie E; Loeffen, Jan; Wesseling, Pieter; Mensenkamp, Arjen; Hoogerbrugge, Nicoline

    2015-01-01

    Constitutional mismatch repair deficiency (CMMR-D) syndrome is characterised by a significantly increased risk for developing cancer in childhood. It arises when both parents have a mutation in the same mismatch repair gene and pass it on to their child. An 8-year-old girl was diagnosed with CMMR-D syndrome after she developed a brain tumour at the age of 4 and a T-cell non-Hodgkin lymphoma at the age of 6. She had multiple hyperpigmented skin lesions and died of myelodysplastic syndrome at the age of 11. In children with cancer CMMR-D syndrome can be recognized particularly if there are multiple primary malignancies and skin hyperpigmentations and hypopigmentations. The parents of these children are at high risk for colorectal and endometrial cancer (Lynch syndrome), amongst others.

  11. The hobbit - an unexpected deficiency.

    Science.gov (United States)

    Hopkinson, Joseph A; Hopkinson, Nicholas S

    2013-12-16

    Vitamin D has been proposed to have beneficial effects in a wide range of contexts. We investigate the hypothesis that vitamin D deficiency, caused by both aversion to sunlight and unwholesome diet, could also be a significant contributor to the triumph of good over evil in fantasy literature. Data on the dietary habits, moral attributes and martial prowess of various inhabitants of Middle Earth were systematically extracted from J R R Tolkien's novel The hobbit. Goodness and victoriousness of characters were scored with binary scales, and dietary intake and habitual sun exposure were used to calculate a vitamin D score (range, 0-4). The vitamin D score was significantly higher among the good and victorious characters (mean, 3.4; SD, 0.5) than the evil and defeated ones (mean, 0.2; SD, 0.4; P fantastic situations and whether randomised intervention trials need to be imagined.

  12. Iron Refractory Iron Deficiency Anaemia: A Rare Cause of Iron Deficiency Anaemia

    LENUS (Irish Health Repository)

    McGrath, T

    2018-01-01

    We describe the case of a 17-month-old boy with a hypochromic microcytic anaemia, refractory to oral iron treatment. After exclusion of dietary and gastrointestinal causes of iron deficiency, a genetic cause for iron deficiency was confirmed by finding two mutations in the TMPRSS6 gene, consistent with a diagnosis of iron-refractory iron deficiency anaemia (IRIDA).

  13. State of cognitive development in children 5-6 years of age with nutritional iron deficiency

    Directory of Open Access Journals (Sweden)

    Chechel V.V.

    2014-06-01

    Full Text Available Features of the development of cognitive functions in children 5-6 years of age with iron deficiency (ID were studied and the relationship of the revealed features of iron deficiency degree was established. After clinical and laboratory examination 205 children aged 5-6 years, pupils of pre-school institutions were included in the study. The core group consisted of 155 children, including 105 children with latent iron deficiency (LID and 50 children with iron deficiency anemia (IDA I degree. The control group consisted of 50 healthy children. To study cognitive function, "Approximate comprehensive program of study of children's readiness for school" was used. A significant decrease of average data of all mental functions (perception, memory, language, thinking, ima¬gination in children 5-6 years old with ID, most pronounced in children with IDA was revealed. Indicators of cognitive functions correspond predominantly to a mild and moderate level of development in children with IDA, the average - in children with LID, good and high - in healthy children. There was a significant direct correlation between the level of cognitive functioning and the level of hemoglobin, serum iron and ferritin. The effect of iron deficiency on the development of indicators of cognitive function toward their reduce in preschool children was established. The level of cognitive functioning depends on the degree of iron deficiency.

  14. Selenium deficiency-induced alterations in ion profiles in chicken muscle.

    Directory of Open Access Journals (Sweden)

    Haidong Yao

    Full Text Available Ion homeostasis plays important roles in development of metabolic diseases. In the present study, we examined the contents and distributions of 25 ions in chicken muscles following treatment with selenium (Se deficiency for 25 days. The results revealed that in chicken muscles, the top ranked microelements were silicon (Si, iron (Fe, zinc (Zn, aluminum (Al, copper (Cu and boron (B, showing low contents that varied from 292.89 ppb to 100.27 ppm. After Se deficiency treatment, essential microelements [Cu, chromium (Cr, vanadium (V and manganese (Mn], and toxic microelements [cadmium (Cd and mercury (Hg] became more concentrated (P < 0.05. Elements distribution images showed generalized accumulation of barium (Ba, cobalt (Co, Cu, Fe and V, while Cr, Mn, and Zn showed pin point accumulations in muscle sections. Thus, the ion profiles were generally influenced by Se deficiency, which suggested a possible role of Se deficiency in muscle dysfunctions caused by these altered ion profiles.

  15. The GH-IGF1 axis and longevity. The paradigm of IGF1 deficiency.

    Science.gov (United States)

    Laron, Zvi

    2008-01-01

    Primary or secondary IGF1 deficiency has been implicated in shortening of lifespan. This paper reviews available data on the influence of IGF1 deficiency on lifespan and longevity in animals and man. It has been shown that inactivation of the IGF1 gene or of the GH receptor in both invertebrates (C-elegans, flies-Drosphila) and rodents (mice and rats), leading to IGF1 deficiency, prolong life, particularly in females. In man, evaluation of the 2 largest cohorts of patients with Laron syndrome (inactive GH receptor resulting in IGF1 deficiency) in Israel and Ecuador revealed that despite their dwarfism and marked obesity, patients are alive at the ages of 75-78 years, with some having reached even more advanced ages. It is assumed that a major contributing factor is their protection from cancer, a major cause of death in the general population.

  16. Fracture in Duchenne Muscular Dystrophy: Natural History and Vitamin D Deficiency.

    Science.gov (United States)

    Perera, Nadia; Sampaio, Hugo; Woodhead, Helen; Farrar, Michelle

    2016-08-01

    The present study examined the natural history of fracture and vitamin D levels in Duchenne muscular dystrophy patients, who are vulnerable to osteoporosis and fractures. Retrospective analysis of a cohort of 48 Duchenne muscular dystrophy patients revealed that 43% of patients experienced ≥1 fracture. Fracture probabilities at ages 6, 9, 12, and 15 years were 4%, 9%, 31%, and 60% respectively, accelerating around the time of ambulation loss (mean age 11.8 ± 2.7 years). Chronic corticosteroid therapy was utilized in 69% of patients and was associated with all vertebral fractures. A history of vitamin D deficiency occurred in 84%, and 35% were currently deficient. Despite chronic vitamin D supplementation, 38% remained deficient. These results demonstrate that osteoporosis and fracture remain major concerns in Duchenne muscular dystrophy. Bone health should be optimized well before loss of ambulation, however current levels of vitamin D supplementation may be inadequate given high levels of deficiency. © The Author(s) 2016.

  17. Ferrotherapy of iron deficiency anemia in children

    OpenAIRE

    Berezhniy V.V.; Korneva V.V.

    2016-01-01

    Present article devoted to the steps for implementation unified clinical protocol of the primary, secondary (specialized) medical care «Iron deficiency» to the practical activities of pediatricians, family physicians. The features of ferrotherapy in children of different age groups and the issues of prevention of iron deficiency states are highlighted.

  18. Circadian behaviour in neuroglobin deficient mice

    DEFF Research Database (Denmark)

    Hundahl, Christian A; Fahrenkrug, Jan; Hay-Schmidt, Anders

    2012-01-01

    on circadian behavior. Ngb-deficient and wild-type (wt) mice were placed in running wheels and their activity rhythms, endogenous period and response to light stimuli were investigated. The effect of Ngb deficiency on the expression of Period1 (Per1) and the immediate early gene Fos was determined after light...

  19. Common micronutrient deficiencies among food aid beneficiaries ...

    African Journals Online (AJOL)

    admin

    Abstract. Background: Ethiopia is amongst the African countries that have received significant food aid. Nonetheless, the common micronutrient deficiencies among food aid beneficiaries are not well documented. Objective: To find out the common micronutrient deficiencies among food aid beneficiaries in the country based ...

  20. Genetics Home Reference: lysosomal acid lipase deficiency

    Science.gov (United States)

    ... lipase deficiency develop multi-organ failure and severe malnutrition and generally do not survive past 1 year. In the later-onset form of lysosomal acid lipase deficiency , signs and symptoms vary and usually begin in mid-childhood, although they can appear anytime up to late ...

  1. Growth hormone deficiency and hyperthermia during exercise

    DEFF Research Database (Denmark)

    Juul, A; Hjortskov, N; Jepsen, Leif

    1995-01-01

    Sweat secretion is often disturbed in patients with GH secretory disorders. Hyperhidrosis is a classic feature of acromegaly, and it has recently been shown that GH-deficient patients exhibit decreased sweating capacity after pilocarpine stimulation of the skin. Thus, patients with GH-deficiency ...

  2. MARGINAL IODINE DEFICIENCY EXACERBATES PERCHLORATE THYROID TOXICITY.

    Science.gov (United States)

    The environmental contaminant perchlorate disrupts thyroid homeostasis via inhibition of iodine uptake into the thyroid. This work tested whether iodine deficiency exacerbates the effects of perchlorate. Female 27 day-old LE rats were fed a custom iodine deficient diet with 0, 50...

  3. Hematopoietic studies in vitamin A deficiency.

    Science.gov (United States)

    Hodges, R E; Sauberlich, H E; Canham, J E; Wallace, D L; Rucker, R B; Mejia, L A; Mohanram, M

    1978-05-01

    Recent studies of experimental vitamin A deficiency in man led the authors to conclude that anemia may result from lack of vitamin A. A review of numerous nutrition surveys in underdeveloped countries enhanced the suspicion that deficiency of vitamin A does contribute to the prevalence of anemia. Preliminary studies of vitamin A-deficient rats confirmed previous observations that anemia may result from lack of this vitamin. The livers of these animals had very low concentrations of vitamin A but normal or increased concentrations of iron. The finding of anemia is in contrast with other reports that vitamin A deficiency may cause elevated values for hemoglobin and hematocrit. The authors suggest that loss of taste and smell as a result of deficiency may account for refusal of experimental animals to eat and drink enough to prevent inanitation and dehydration. The resulting hemoconcentration may mask the true hematological picture, which is one of anemia.

  4. Japanese family with congenital factor VII deficiency.

    Science.gov (United States)

    Sakakibara, Kanae; Okayama, Yoshiki; Fukushima, Kenji; Kaji, Shunsaku; Muraoka, Michiko; Arao, Yujiro; Shimada, Akira

    2015-10-01

    Congenital factor VII (FVII) deficiency is a rare bleeding disorder with autosomal recessive inheritance. The present female patient was diagnosed with congenital FVII deficiency because of low hepaplastin test (HPT), although vitamin K was given. Heterozygous p.A191T mutation was detected in the peripheral blood, and the same mutation was also found in the mother and sister. To the best of our knowledge, this is the fourth reported case of p.A191T mutation of FVII in the literature and the first to be reported in Japan. FVII coagulation activity (FVII:C) in asymptomatic heterozygous carriers is mildly reduced. Therefore, some patients may not be accurately diagnosed with congenital FVII deficiency. In infants with low HPT without vitamin K deficiency, congenital FVII deficiency should be considered. © 2015 Japan Pediatric Society.

  5. Subacute copper-deficiency myelopathy in a patient with occult celiac disease.

    Science.gov (United States)

    Cavallieri, Francesco; Fini, Nicola; Contardi, Sara; Fiorini, Massimo; Corradini, Elena; Valzania, Franco

    2017-07-01

    Acquired copper deficiency represents a rare cause of progressive myelopathy presenting with sensory ataxia and spastic gait. The time interval from neurological symptoms onset to diagnosis of myelopathy ranges from 2 months to several years in almost all cases, mimicking the clinical course of subacute combined degeneration due to vitamin B12 deficiency. A 60-year-old man, without any gastrointestinal symptoms, developed over the course of one week rapidly progressive gait imbalance, tingling and numbness in his feet and ascending lower limb weakness. Spine magnetic resonance imaging revealed hyperintensity involving cervical and dorsal posterior columns of spinal cord. Blood analysis revealed undetectable serum copper levels, low serum ceruloplasmin and positive serum Immunoglobulin A anti-tissue transglutaminase. Upper gastrointestinal endoscopy was performed revealing duodenal villous atrophy consistent with a malabsorption pattern. A gluten-free diet in association with intravenous then oral copper supplementation prompted sustained normalization of serum copper levels and progressive clinical improvement. We report a rare case of myelopathy induced by copper deficiency secondary to undiagnosed celiac disease, peculiarly presenting with a subacute onset. This case expands the neurological presentation and clinical course of myelopathy due to acquired copper deficiency. We suggest investigation of copper deficiency in patients presenting with subacute or even acute sensory ataxia and spastic gait. Detection of hypocupremia in patients without a previous history of gastric surgery should lead to diagnostic testing for celiac disease even in the absence of any obvious gastrointestinal symptoms.

  6. Latent manganese deficiency increases transpiration in barley (Hordeum vulgare).

    Science.gov (United States)

    Hebbern, Christopher A; Laursen, Kristian Holst; Ladegaard, Anne H; Schmidt, Sidsel B; Pedas, Pai; Bruhn, Dan; Schjoerring, Jan K; Wulfsohn, Dvoralai; Husted, Søren

    2009-03-01

    To investigate if latent manganese (Mn) deficiency leads to increased transpiration, barley plants were grown for 10 weeks in hydroponics with daily additions of Mn in the low nM range. The Mn-starved plants did not exhibit visual leaf symptoms of Mn deficiency, but Chl a fluorescence measurements revealed that the quantum yield efficiency of PSII (F(v)/F(m)) was reduced from 0.83 in Mn-sufficient control plants to below 0.5 in Mn-starved plants. Leaf Mn concentrations declined from 30 to 7 microg Mn g(-1) dry weight in control and Mn-starved plants, respectively. Mn-starved plants had up to four-fold higher transpiration than control plants. Stomatal closure and opening upon light/dark transitions took place at the same rate in both Mn treatments, but the nocturnal leaf conductance for water vapour was still twice as high in Mn-starved plants compared with the control. The observed increase in transpiration was substantiated by (13)C-isotope discrimination analysis and gravimetric measurement of the water consumption, showing significantly lower water use efficiency in Mn-starved plants. The extractable wax content of leaves of Mn-starved plants was approximately 40% lower than that in control plants, and it is concluded that the increased leaf conductance and higher transpirational water loss are correlated with a reduction in the epicuticular wax layer under Mn deficiency.

  7. The triad of Iron deficiency anemia, hepatosplenomegaly and ...

    African Journals Online (AJOL)

    2014-12-04

    Dec 4, 2014 ... In conclusion, iron deficiency anemia occurring in the triad without zinc deficiency as .... a negative zinc balance and mask existing zinc deficiency.[10] ... erythropoiesis‑stimulating agents in men with chronic kidney disease.

  8. Genetics Home Reference: ataxia with vitamin E deficiency

    Science.gov (United States)

    ... Conditions Ataxia with vitamin E deficiency Ataxia with vitamin E deficiency Printable PDF Open All Close All Enable ... view the expand/collapse boxes. Description Ataxia with vitamin E deficiency is a disorder that impairs the body's ...

  9. Genetics Home Reference: X-linked creatine deficiency

    Science.gov (United States)

    ... Health Conditions X-linked creatine deficiency X-linked creatine deficiency Printable PDF Open All Close All Enable ... view the expand/collapse boxes. Description X-linked creatine deficiency is an inherited disorder that primarily affects ...

  10. Genetics Home Reference: carnitine-acylcarnitine translocase deficiency

    Science.gov (United States)

    ... Email Facebook Twitter Home Health Conditions CACT deficiency Carnitine-acylcarnitine translocase deficiency Printable PDF Open All Close ... Javascript to view the expand/collapse boxes. Description Carnitine-acylcarnitine translocase (CACT) deficiency is a condition that ...

  11. Genetic, molecular and functional analyses of complement factor I deficiency

    DEFF Research Database (Denmark)

    Nilsson, S.C.; Trouw, L.A.; Renault, N.

    2009-01-01

    Complete deficiency of complement inhibitor factor I (FI) results in secondary complement deficiency due to uncontrolled spontaneous alternative pathway activation leading to susceptibility to infections. Current genetic examination of two patients with near complete FI deficiency and three patie...

  12. Genetics Home Reference: iron-refractory iron deficiency anemia

    Science.gov (United States)

    ... refractory iron deficiency anemia Iron-refractory iron deficiency anemia Printable PDF Open All Close All Enable Javascript ... expand/collapse boxes. Description Iron-refractory iron deficiency anemia is one of many types of anemia , which ...

  13. Iron Deficiency Anaemia In Reproductive Age Women Attending ...

    African Journals Online (AJOL)

    Iron Deficiency Anaemia In Reproductive Age Women Attending Obstetrics And ... prevalence of iron deficiency anemia in reproductive age women, and their relation to ... Thus iron deficiency anemia during pregnancy in well-educated set up ...

  14. Zinc Deficiency-Like Syndrome in Fleckvieh Calves: Clinical and Pathological Findings and Differentiation from Bovine Hereditary Zinc Deficiency.

    Science.gov (United States)

    Langenmayer, M C; Jung, S; Majzoub-Altweck, M; Trefz, F M; Seifert, C; Knubben-Schweizer, G; Fries, R; Hermanns, W; Gollnick, N S

    2018-03-01

    Zinc deficiency-like (ZDL) syndrome is an inherited defect of Fleckvieh calves, with striking similarity to bovine hereditary zinc deficiency (BHZD). However, the causative mutation in a phospholipase D4 encoding gene (PLD4) shows no connection to zinc metabolism. To describe clinical signs, laboratory variables, and pathological findings of ZDL syndrome and their utility to differentiate ZDL from BHZD and infectious diseases with similar phenotype. Nine hospitalized calves with crusting dermatitis and confirmed mutation in PLD4 and medical records from 25 calves with crusting dermatitis or suspected zinc deficiency. Prospective and retrospective case series. The 9 calves (age: 5-53 weeks) displayed a moderate to severe crusting dermatitis mainly on the head, ventrum, and joints. Respiratory and digestive tract inflammations were frequently observed. Zinc supplementation did not lead to remission of clinical signs in 4 calves. Laboratory variables revealed slight anemia in 8 calves, hypoalbuminemia in 6 calves, but reduced serum zinc concentrations in only 3 calves. Mucosal erosions/ulcerations were present in 7 calves and thymus atrophy or reduced thymic weights in 8 calves. Histologically, skin lesions were indistinguishable from BHZD. Retrospective analysis of medical records revealed the presence of this phenotype since 1988 and pedigree analysis revealed a common ancestor of several affected calves. ZDL syndrome should be suspected in Fleckvieh calves with crusting dermatitis together with diarrhea or respiratory tract inflammations without response to oral zinc supplementation. Definite diagnosis requires molecular genetic confirmation of the PLD4 mutation. Copyright © 2018 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  15. Seventeen Alpha-hydroxylase Deficiency

    Directory of Open Access Journals (Sweden)

    Siew-Lee Wong

    2006-01-01

    Full Text Available Seventeen a-hydroxylase deficiency (17OHD is a rare form of congenital adrenal hyperplasia in which defects in the biosynthesis of cortisol and sex steroid result in mineralocorticoid excess, hypokalemic hypertension and sexual abnormalities such as pseudohermaphroditism in males, and sexual infantilism in females. The disease is inherited in an autosomal recessive pattern, and is caused by mutations in the gene encoding cytochrome P450c17 (CYP17, which is the single polypeptide that mediates both 17α-hydroxylase and 17,20-lyase activities. We report the case of a 15-year-old patient with 17OHD who had a female phenotype but male karyotype (46,XY. The diagnosis was made based on classical clinical features, biochemical data and molecular genetic study. Two mutations were identified by polymerase chain reaction amplification and sequencing, including a S106P point mutation in exon 2 and a 9-bp (GACTCTTTC deletion from nucleotide position 1519 in exon 8 of CYP17. The first of these mutations was found in the father and the second in the mother, and both have been previously reported in Asia. The patient's hypertension and hypokalemia resolved after glucocorticoid replacement and treatment with potassium-sparing diuretics. Sex hormone replacement was prescribed for induction of sexual development and reduction of the final height. Prophylactic gonadectomy was scheduled. In summary, 17OHD should be suspected in patients with hypokalemic hypertension and lack of secondary sexual development so that appropriate therapy can be implemented.

  16. Melanocortin 1 Receptor Deficiency Promotes Atherosclerosis in Apolipoprotein E-/- Mice.

    Science.gov (United States)

    Rinne, Petteri; Kadiri, James J; Velasco-Delgado, Mauricio; Nuutinen, Salla; Viitala, Miro; Hollmén, Maija; Rami, Martina; Savontaus, Eriika; Steffens, Sabine

    2018-02-01

    The MC1-R (melanocortin 1 receptor) is expressed by monocytes and macrophages where it mediates anti-inflammatory actions. MC1-R also protects against macrophage foam cell formation primarily by promoting cholesterol efflux through the ABCA1 (ATP-binding cassette transporter subfamily A member 1) and ABCG1 (ATP-binding cassette transporter subfamily G member 1). In this study, we aimed to investigate whether global deficiency in MC1-R signaling affects the development of atherosclerosis. Apoe -/- (apolipoprotein E deficient) mice were crossed with recessive yellow (Mc1r e/e ) mice carrying dysfunctional MC1-R and fed a high-fat diet to induce atherosclerosis. Apoe -/- Mc1r e/e mice developed significantly larger atherosclerotic lesions in the aortic sinus and in the whole aorta compared with Apoe -/- controls. In terms of plaque composition, MC1-R deficiency was associated with less collagen and smooth muscle cells and increased necrotic core, indicative of more vulnerable lesions. These changes were accompanied by reduced Abca1 and Abcg1 expression in the aorta. Furthermore, Apoe -/- Mc1r e/e mice showed a defect in bile acid metabolism that aggravated high-fat diet-induced hypercholesterolemia and hepatic lipid accumulation. Flow cytometric analysis of leukocyte profile revealed that dysfunctional MC1-R enhanced arterial accumulation of classical Ly6C high monocytes and macrophages, effects that were evident in mice fed a normal chow diet but not under high-fat diet conditions. In support of enhanced arterial recruitment of Ly6C high monocytes, these cells had increased expression of L-selectin and P-selectin glycoprotein ligand 1. The present study highlights the importance of MC1-R in the development of atherosclerosis. Deficiency in MC1-R signaling exacerbates atherosclerosis by disturbing cholesterol handling and by increasing arterial monocyte accumulation. © 2017 The Authors.

  17. Zinc: physiology, deficiency, and parenteral nutrition.

    Science.gov (United States)

    Livingstone, Callum

    2015-06-01

    The essential trace element zinc (Zn) has a large number of physiologic roles, in particular being required for growth and functioning of the immune system. Adaptive mechanisms enable the body to maintain normal total body Zn status over a wide range of intakes, but deficiency can occur because of reduced absorption or increased gastrointestinal losses. Deficiency impairs physiologic processes, leading to clinical consequences that include failure to thrive, skin rash, and impaired wound healing. Mild deficiency that is not clinically overt may still cause nonspecific consequences, such as susceptibility to infection and poor growth. The plasma Zn concentration has poor sensitivity and specificity as a test of deficiency. Consequently, diagnosis of deficiency requires a combination of clinical assessment and biochemical tests. Patients receiving parenteral nutrition (PN) are susceptible to Zn deficiency and its consequences. Nutrition support teams should have a strategy for assessing Zn status and optimizing this by appropriate supplementation. Nutrition guidelines recommend generous Zn provision from the start of PN. This review covers the physiology of Zn, the consequences of its deficiency, and the assessment of its status, before discussing its role in PN. © 2015 American Society for Parenteral and Enteral Nutrition.

  18. Reticulocyte maturity indices in iron deficiency anemia

    Directory of Open Access Journals (Sweden)

    Muriel Wollmann

    2014-01-01

    Full Text Available Objective: The aim of this study was to analyze the reticulocyte maturity indices (low, medium, and high fluorescence ratios in iron deficient 1- to 6-year-old children, and identify the prevalence of iron deficiency anemia in this population. Methods: The present study included 39 subjects, divided into two groups: control subjects (n = 33, and subjects with iron deficiency anemia (n = 6. The results were analyzed by Student's t-test for comparison of means. Differences were considered significant when two-tailed p-value < 0.05. Results: Subjects with iron deficiency anemia presented increases in the proportion of mean (10.3 ± 4.7% vs. 6.0 ± 3.4%; p-value = 0.003, and high fluorescence reticulocytes (2.3 ± 0.87% vs. 0.9 ± 0.9%; p-value = 0.03 compared to the control group. The prevalence of anemia in this population was 15% (n = 6. Conclusion: The indices related to immaturity of reticulocytes are higher in the presence of iron deficiency, thus demonstrating a deficiency in the raw material to form hemoglobin and are, therefore, possible early markers of iron deficiency and anemia. We emphasize the need to standardize these indices for use in clinical practice and lab test results.

  19. Transient multiple acyl-CoA dehydrogenation deficiency in a newborn female caused by maternal riboflavin deficiency

    DEFF Research Database (Denmark)

    Chiong, M A; Sim, K G; Carpenter, K

    2007-01-01

    in intact fibroblasts both in normal and riboflavin depleted media showed normal oxidation of fatty acids excluding defects in electron transfer flavoprotein (ETF), or ETF ubiquinone oxidoreductase (ETF:QO), or a genetic abnormality in flavin metabolism. In addition, sequencing of the genes encoding ETF...... and ETF:QO in the proband did not reveal any pathogenic mutations. Determination of the maternal riboflavin status after delivery showed that the mother was riboflavin deficient. Repeat testing done two years after the infant's birth and while on a normal diet showed that the mother was persistently...

  20. Biotinidase deficiency presenting as recurrent myelopathy in a 7-year-old boy and a review of the literature.

    Science.gov (United States)

    Raha, Sarbani; Udani, Vrajesh

    2011-10-01

    Biotinidase deficiency may produce variable neurologic manifestations. Brainstem and spinal cord disease comprises an uncommon presentation of biotinidase deficiency. We describe a 7-year old boy with subacute progressive quadriplegia and "sighing" respirations. Severe biotinidase deficiency was established, and the patient demonstrated complete recovery with biotin supplementation. Genetic studies revealed presence of homozygous mutation in the BTD gene [c.133C>T (p.H447Y)]. Biotinidase deficiency should be considered in the differential diagnosis for subacute, long segment myelopathy, particularly with brainstem involvement. This entity is treatable; a high index of suspicion can be life-saving. We also review the literature on biotinidase deficiency presenting as spinal cord demyelinating disease. Copyright © 2011 Elsevier Inc. All rights reserved.

  1. Syndromes associated with nutritional deficiency and excess.

    Science.gov (United States)

    Jen, Melinda; Yan, Albert C

    2010-01-01

    Normal functioning of the human body requires a balance between nutritional intake and metabolism, and imbalances manifest as nutritional deficiencies or excess. Nutritional deficiency states are associated with social factors (war, poverty, famine, and food fads), medical illnesses with malabsorption (such as Crohn disease, cystic fibrosis, and after bariatric surgery), psychiatric illnesses (eating disorders, autism, alcoholism), and medications. Nutritional excess states result from inadvertent or intentional excessive intake. Cutaneous manifestations of nutritional imbalance can herald other systemic manifestations. This contribution discusses nutritional deficiency and excess syndromes with cutaneous manifestations of particular interest to clinical dermatologists. Copyright © 2010. Published by Elsevier Inc.

  2. 2-Methylbutyryl-coenzyme A dehydrogenase deficiency

    DEFF Research Database (Denmark)

    Sass, Jörn Oliver; Ensenauer, Regina; Röschinger, Wulf

    2008-01-01

    2-Methylbutyryl-CoA dehydrogenase (MBD; coded by the ACADSB gene) catalyzes the step in isoleucine metabolism that corresponds to the isovaleryl-CoA dehydrogenase reaction in the degradation of leucine. Deficiencies of both enzymes may be detected by expanded neonatal screening with tandem...... individuals showed clinical symptoms attributable to MBD deficiency although the defect in isoleucine catabolism was demonstrated both in vivo and in vitro. Several mutations in the ACADSB gene were identified, including a novel one. MBD deficiency may be a harmless metabolic variant although significant...

  3. [Vitamin B12 deficiency: what's new?].

    Science.gov (United States)

    Braillard, O; Casini, A; Samii, K; Rufenacht, P; Junod, Perron N

    2012-09-26

    Vitamin B12 screening is only recommended among symptomatic patients or in those with risk factors. The main cause of vitamin B12 deficiency is the food cobalamin malabsorption syndrom. Holotranscobalamin is a more reliable marker than cyanocobalamin to confirm vitamin B12 deficiency, but it has not been validated yet in complex situations. An autoimmune gastritis must be excluded in the absence of risk factors but in the presence of a probable deficiency. Oral substitution treatment is effective but requires excellent therapeutic compliance and close follow-up to monitor the response to treatment. It has not yet been studied among patients suffering from severe symptoms, inflammatory bowel disease and ileal resection.

  4. Hypopituitarism: growth hormone and corticotropin deficiency.

    Science.gov (United States)

    Capatina, Cristina; Wass, John A H

    2015-03-01

    This article presents an overview of adult growth hormone deficiency (AGHD) and corticotropin deficiency (central adrenal failure, CAI). Both conditions can result from various ailments affecting the hypothalamus or pituitary gland (most frequently a tumor in the area or its treatment). Clinical manifestations are subtle in AGHD but potentially life-threatening in CAI. The diagnosis needs dynamic testing in most cases. Treatment of AGHD is recommended in patients with documented severe deficiency, and treatment of CAI is mandatory in all cases. Despite significant progress in replacement hormonal therapy, more physiologic treatments and more reliable indicators of treatment adequacy are still needed. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Prevalence of Vitamin B12 and Folate Deficiencies and ...

    African Journals Online (AJOL)

    ... 2Faculty of Dentistry, International Branch, 3Department of Internal Medicine & Endocrine and ... Keywords: Vitamin B12 deficiency, Folate deficiency, Homocysteinemia, Elderly population ... gastritis, intestinal malabsorption, pancreatic.

  6. Vitamin paradox in obesity: Deficiency or excess?

    Science.gov (United States)

    Zhou, Shi-Sheng; Li, Da; Chen, Na-Na; Zhou, Yiming

    2015-08-25

    Since synthetic vitamins were used to fortify food and as supplements in the late 1930s, vitamin intake has significantly increased. This has been accompanied by an increased prevalence of obesity, a condition associated with diabetes, hypertension, cardiovascular disease, asthma and cancer. Paradoxically, obesity is often associated with low levels of fasting serum vitamins, such as folate and vitamin D. Recent studies on folic acid fortification have revealed another paradoxical phenomenon: obesity exhibits low fasting serum but high erythrocyte folate concentrations, with high levels of serum folate oxidation products. High erythrocyte folate status is known to reflect long-term excess folic acid intake, while increased folate oxidation products suggest an increased folate degradation because obesity shows an increased activity of cytochrome P450 2E1, a monooxygenase enzyme that can use folic acid as a substrate. There is also evidence that obesity increases niacin degradation, manifested by increased activity/expression of niacin-degrading enzymes and high levels of niacin metabolites. Moreover, obesity most commonly occurs in those with a low excretory reserve capacity (e.g., due to low birth weight/preterm birth) and/or a low sweat gland activity (black race and physical inactivity). These lines of evidence raise the possibility that low fasting serum vitamin status in obesity may be a compensatory response to chronic excess vitamin intake, rather than vitamin deficiency, and that obesity could be one of the manifestations of chronic vitamin poisoning. In this article, we discuss vitamin paradox in obesity from the perspective of vitamin homeostasis.

  7. Identical substitutions in magnesium chelatase paralogs result in chlorophyll deficient soybean mutants

    Science.gov (United States)

    The soybean (Glycine max (L.) Merr.) chlorophyll deficient line MinnGold is a spontaneous mutant characterized by yellow foliage. Map-based cloning and transgenic complementation revealed that the mutant phenotype is caused by a non-synonymous nucleotide substitution in the third exon of a Mg-chelat...

  8. Growth hormone deficiency and pituitary malformation in a recurrent Cat-Eye syndrome: a family report.

    Science.gov (United States)

    Jedraszak, Guillaume; Braun, Karine; Receveur, Aline; Decamp, Matthieu; Andrieux, Joris; Rabbind Singh, Amrathlal; Copin, Henri; Bremond-Gignac, Dominique; Mathieu, Michèle; Rochette, Jacques; Morin, Gilles

    2015-10-01

    Growth hormone deficiency affects roughly between one in 3000 and one in 4000 children with most instances of growth hormone deficiency being idiopathic. Growth hormone deficiency can also be associated with genetic diseases or chromosome abnormalities. Association of growth hormone deficiency together with hypothalamic-pituitary axis malformation and Cat-Eye syndrome is a very rare condition. We report a family with two brothers presenting with growth delay due to a growth hormone deficiency associated with a polymalformation syndrome. They both displayed pre-auricular pits and tags, imperforate anus and Duane retraction syndrome. Both parents and a third unaffected son displayed normal growth pattern. Cerebral MRI showed a hypothalamic-pituitary axis malformation in the two affected brothers. Cytogenetic studies revealed a type I small supernumerary marker chromosome derived from chromosome 22 resulting in a tetrasomy 22pter-22q11.21 characteristic of the Cat-Eye syndrome. The small supernumerary marker chromosome was present in the two affected sons and the mother in a mosaic state. Patients with short stature due to growth hormone deficiency should be evaluated for chromosomal abnormality. Family study should not be underestimated. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  9. Alterations of proteins in MDCK cells during acute potassium deficiency.

    Science.gov (United States)

    Peerapen, Paleerath; Ausakunpipat, Nardtaya; Chanchaem, Prangwalai; Thongboonkerd, Visith

    2016-06-01

    Chronic K(+) deficiency can cause hypokalemic nephropathy associated with metabolic alkalosis, polyuria, tubular dilatation, and tubulointerstitial injury. However, effects of acute K(+) deficiency on the kidney remained unclear. This study aimed to explore such effects by evaluating changes in levels of proteins in renal tubular cells during acute K(+) deficiency. MDCK cells were cultivated in normal K(+) (NK) (K(+)=5.3 mM), low K(+) (LK) (K(+)=2.5 mM), or K(+) depleted (KD) (K(+)=0 mM) medium for 24 h and then harvested. Cellular proteins were resolved by two-dimensional gel electrophoresis (2-DE) and visualized by SYPRO Ruby staining (5 gels per group). Spot matching and quantitative intensity analysis revealed a total 48 protein spots that had significantly differential levels among the three groups. Among these, 46 and 30 protein spots had differential levels in KD group compared to NK and LK groups, respectively. Comparison between LK and NK groups revealed only 10 protein spots that were differentially expressed. All of these differentially expressed proteins were successfully identified by Q-TOF MS and/or MS/MS analyses. The altered levels of heat shock protein 90 (HSP90), ezrin, lamin A/C, tubulin, chaperonin-containing TCP1 (CCT1), and calpain 1 were confirmed by Western blot analysis. Global protein network analysis showed three main functional networks, including 1) cell growth and proliferation, 2) cell morphology, cellular assembly and organization, and 3) protein folding in which the altered proteins were involved. Further investigations on these networks may lead to better understanding of pathogenic mechanisms of low K(+)-induced renal injury. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Impulsivity: A deficiency of inhibitory control?

    NARCIS (Netherlands)

    Lansbergen, M.M.

    2007-01-01

    Impulsivity has been defined as acting without thinking. Impulsivity can be quantified by impulsivity questionnaires, but also by behavioral paradigms which tax inhibitory control. Previous research has repeatedly demonstrated deficient inhibitory control in psychopathological samples characterized

  11. Genetics Home Reference: factor XIII deficiency

    Science.gov (United States)

    ... XIII deficiency tend to have heavy or prolonged menstrual bleeding (menorrhagia) and may experience recurrent pregnancy losses ( ... inheritance, which means that it results when both copies of either the F13A1 gene or the F13B ...

  12. Vitamin K deficiency bleeding of the newborn

    Science.gov (United States)

    Vitamin K deficiency bleeding of the newborn (VKDB) is a bleeding disorder in babies. It most often ... A lack of vitamin K may cause severe bleeding in newborn babies. Vitamin K plays an important role in blood clotting. Babies often ...

  13. Somatomedin C deficiency in Asian sisters.

    OpenAIRE

    McGraw, M E; Price, D A; Hill, D J

    1986-01-01

    Two sisters of Asian origin showed typical clinical and biochemical features of primary somatomedin C (SM-C) deficiency (Laron dwarfism). Abnormalities of SM-C binding proteins were observed, one sister lacking the high molecular weight (150 Kd) protein.

  14. Genetics Home Reference: cerebral folate transport deficiency

    Science.gov (United States)

    ... R. Cerebral folate deficiency syndromes in childhood: clinical, analytical, and etiologic aspects. Arch Neurol. 2011 May;68( ... 2009.08.005. Citation on PubMed or Free article on PubMed Central Toelle SP, Wille D, Schmitt ...

  15. CALCIUM DEFICIENCY AND CAUSATION OF RICKETS IN ...

    African Journals Online (AJOL)

    hi-tech

    2005-03-03

    Mar 3, 2005 ... communication about the benefits of exposing children to sunlight is very important in preventing the ... of rickets was nutritional deficiency of vitamin D due either to ..... resulting from less time being spent outdoors is the cause.

  16. Defense Logistics Agency Product Quality Deficiency Program

    National Research Council Canada - National Science Library

    1998-01-01

    .... He was interested in improving the product quality deficiency report system, which is used by DoD Components to identify and purge nonconforming material from inventory and to provide information...

  17. LACTASE DEFICIENCY IN BABIES AND INFANTS

    Directory of Open Access Journals (Sweden)

    E.A. Kornienko

    2006-01-01

    Full Text Available Lactose, the constituent disaccharide of milk and other dairy products, is an important nutrient in early childhood. Lactase breaks down lactose in small intestine. In most people the activity of lactase reduces with age. In infancy lactase deficiency tends to be either transient, which is more often, or secondary to intestinal diseases. Abdominal cramps, anxiety and dyspepsia are the common symptoms of lactase deficiency. Tactics of treatment should take into account a cause and severity of the condition. A specialized milk formula «enfamil lactofree», distinguished for its' optimal formulation, high clinical effectiveness and good tolerance, could be recommended for use in children with primary, transient and secondary lactase deficiency who receive formula and mixed feeding.Key words: lactose, lactase deficiency, lactose-free formula.

  18. Prenatal diagnosis in adenylosuccinate lyase deficiency

    NARCIS (Netherlands)

    Marie, S.; Flipsen, J. W.; Duran, M.; Poll-The, B. T.; Beemer, F. A.; Bosschaart, A. N.; Vincent, M. F.; van den Berghe, G.

    2000-01-01

    Adenylosuccinate lyase deficiency, an autosomal recessive inborn error of purine synthesis, provokes accumulation in body fluids of succinylaminoimidazolecarboxamide riboside and succinyladenosine, the dephosphorylated derivatives of the two substrates of the enzyme. Most patients display severe

  19. Genetics Home Reference: GABA-transaminase deficiency

    Science.gov (United States)

    ... Description GABA-transaminase deficiency is a brain disease (encephalopathy) that begins in infancy. Babies with this disorder ... genetic testing? What is precision medicine? What is newborn screening? New Pages LMNA-related congenital muscular dystrophy ...

  20. Neurological findings in triosephosphate isomerase deficiency

    NARCIS (Netherlands)

    Poll-The, B. T.; Aicardi, J.; Girot, R.; Rosa, R.

    1985-01-01

    Two siblings with hemolytic anemia caused by triosephosphate isomerase deficiency developed a progressive neurological syndrome featuring dystonic movements, tremor, pyramidal tract signs, and evidence of spinal motor neuron involvement. Intelligence was unaffected. The findings in these patients

  1. VITAMIN A DEFICIENCY IN NIGERIAN CHILDREN

    African Journals Online (AJOL)

    Dr Olaleye

    Vitamin A deficiency (VAD) is a global problem of public health significance in many ... It is therefore important to know Vitamin A status of. Nigerian ..... Ph D thesis University of Ibadan. Ajaiyeoba AI (1994). Childhood blindness in Nigeria.

  2. Genetics Home Reference: familial glucocorticoid deficiency

    Science.gov (United States)

    ... deficiency Patient Support and Advocacy Resources (5 links) Australian Pituitary Foundation: An Introduction to Adrenal Insufficiency in ... API Site Map Subscribe Customer Support USA.gov Copyright Privacy Accessibility FOIA Viewers & Players U.S. Department of ...

  3. Isoprenoid biosynthesis and mevalonate kinase deficiency

    NARCIS (Netherlands)

    Henneman, L.

    2011-01-01

    Mevalonaat Kinase Deficiëntie (MKD) is een aangeboren ziekte geassocieerd met heftige koortsaanvallen die drie tot vier dagen aanhouden en gepaard gaan met koude rillingen, gewrichtsklachten, huiduitslag, hoofdpijn, duizeligheid, buikpijn, braken en diarree. De koortsaanvallen treden gemiddeld eens

  4. FastStats: Anemia or Iron Deficiency

    Science.gov (United States)

    ... this? Submit What's this? Submit Button NCHS Home Anemia or Iron Deficiency Recommend on Facebook Tweet Share ... visits Number of visits to emergency departments with anemia as the primary hospital discharge diagnosis: 188,000 ...

  5. Genetics Home Reference: isolated sulfite oxidase deficiency

    Science.gov (United States)

    ... and Management Resources (1 link) GeneReview: Isolated Sulfite Oxidase Deficiency General Information from MedlinePlus (5 links) Diagnostic Tests Drug Therapy Genetic Counseling Palliative Care Surgery and ...

  6. Experimental reproduction of iodine deficiency in cattle.

    Science.gov (United States)

    McCoy, M A; Smyth, J A; Ellis, W A; Arthur, J R; Kennedy, D G

    1997-11-22

    The role of iodine deficiency in stillbirth/perinatal weak calf syndrome was investigated in pregnant heifers. Five heifers were fed an iodine deficient diet (mean [sd] iodine concentration 0.06 [0.01] mg/kg dry matter [DM]) and six received an iodine sufficient diet (mean [sd] iodine concentration 1.45 [0.27] mg/kg DM). The diets consisted of wheat and soyabean meal with added minerals and vitamins (with or without iodine) and were fed to the heifers over the final four to five months of pregnancy. The iodine deficient diet produced clinicopathological changes and pathological changes in the thyroid glands of both the heifers and their offspring. However, all the calves in the iodine deficient group were born clinically normal.

  7. Office ergonomics: deficiencies in computer workstation design.

    Science.gov (United States)

    Shikdar, Ashraf A; Al-Kindi, Mahmoud A

    2007-01-01

    The objective of this research was to study and identify ergonomic deficiencies in computer workstation design in typical offices. Physical measurements and a questionnaire were used to study 40 workstations. Major ergonomic deficiencies were found in physical design and layout of the workstations, employee postures, work practices, and training. The consequences in terms of user health and other problems were significant. Forty-five percent of the employees used nonadjustable chairs, 48% of computers faced windows, 90% of the employees used computers more than 4 hrs/day, 45% of the employees adopted bent and unsupported back postures, and 20% used office tables for computers. Major problems reported were eyestrain (58%), shoulder pain (45%), back pain (43%), arm pain (35%), wrist pain (30%), and neck pain (30%). These results indicated serious ergonomic deficiencies in office computer workstation design, layout, and usage. Strategies to reduce or eliminate ergonomic deficiencies in computer workstation design were suggested.

  8. Thyroid disorders in mild iodine deficiency

    DEFF Research Database (Denmark)

    Laurberg, P; Nøhr, S B; Pedersen, K M

    2000-01-01

    Comparative epidemiologic studies in areas with low and high iodine intake and controlled studies of iodine supplementation have demonstrated that the major consequence of mild-to-moderate iodine deficiency for the health of the population is an extraordinarily high occurrence of hyperthyroidism...... endangered but the consequences of severe iodine deficiency for brain development are grave and a considerable safety margin is advisable. Moreover, a shift toward less malignant types of thyroid cancer and a lower radiation dose to the thyroid in case of nuclear fallout support that mild-to-moderate iodine...... deficiency should be corrected. However, there is evidence that a high iodine intake may be associated with more autoimmune hypothyroidism, and that Graves' disease may manifest at a younger age and be more difficult to treat. Hence, the iodine intake should be brought to a level at which iodine deficiency...

  9. Study of neutron-deficient Sn isotopes

    International Nuclear Information System (INIS)

    Auger, G.

    1982-05-01

    The formation of neutron deficient nuclei by heavy ion reactions is investigated. The experimental technique is presented, and the results obtained concerning Sn et In isotopes reported: first excited states of 106 Sn, high spin states in 107 Sn and 107 In; Yrast levels of 106 Sn, 107 Sn, 108 Sn; study of neutron deficient Sn and In isotopes formed by the desintegration of the compound nucleus 112 Xe. All these results are discussed [fr

  10. Iron deficiency and anemia in heart failure.

    Science.gov (United States)

    Çavuşoğlu, Yüksel; Altay, Hakan; Çetiner, Mustafa; Güvenç, Tolga Sinan; Temizhan, Ahmet; Ural, Dilek; Yeşilbursa, Dilek; Yıldırım, Nesligül; Yılmaz, Mehmet Birhan

    2017-03-01

    Heart failure is an important community health problem. Prevalence and incidence of heart failure have continued to rise over the years. Despite recent advances in heart failure therapy, prognosis is still poor, rehospitalization rate is very high, and quality of life is worse. Co-morbidities in heart failure have negative impact on clinical course of the disease, further impair prognosis, and add difficulties to treatment of clinical picture. Therefore, successful management of co-morbidities is strongly recommended in addition to conventional therapy for heart failure. One of the most common co-morbidities in heart failure is presence of iron deficiency and anemia. Current evidence suggests that iron deficiency and anemia are more prevalent in patients with heart failure and reduced ejection fraction, as well as those with heart failure and preserved ejection fraction. Moreover, iron deficiency and anemia are referred to as independent predictors for poor prognosis in heart failure. There is strong relationship between iron deficiency or anemia and severity of clinical status of heart failure. Over the last two decades, many clinical investigations have been conducted on clinical effectiveness of treatment of iron deficiency or anemia with oral iron, intravenous iron, and erythropoietin therapies. Studies with oral iron and erythropoietin therapies did not provide any clinical benefit and, in fact, these therapies have been shown to be associated with increase in adverse clinical outcomes. However, clinical trials in patients with iron deficiency in the presence or absence of anemia have demonstrated considerable clinical benefits of intravenous iron therapy, and based on these positive outcomes, iron deficiency has become target of therapy in management of heart failure. The present report assesses current approaches to iron deficiency and anemia in heart failure in light of recent evidence.

  11. Deficiency and sources of nutrition among an Indian tribal population.

    Science.gov (United States)

    Ghosh, Sudipta

    2014-09-01

    This paper is an attempt to explore the relationship between protein consumption and BMI for the adult Santhals, a tribal community of West Bengal, India. For this purpose, a cross sectional sample of 1262 adult Santhals were mea- sured. A high incidence (46.9%) of chronic energy deficiency (CED) is observed. A low production of protein rich food items such as pulses, poultry and fishing within their own economy reveal that the barter system fails to provide enough protein rich food items for the community. Along with this, low income earning opportunities lead to a low consumption of protein rich food and hence a high incidence of undernutrition. The occupational pattern reveals that the Santhals who derive livelihood by the means of hard physical activities are more prone to develop CED. The study suggests that the overdependence on forests and their own economy for consumption needs may not be helping this community in attaining a better health status.

  12. Vitamin B12 deficiency presenting as acute ataxia.

    Science.gov (United States)

    Crawford, John Ross; Say, Daphne

    2013-03-26

    A previously healthy 7-year-old Caucasian boy was hospitalised for evaluation of acute ataxia and failure to thrive, initially suspicious for an intracranial mass. Weight and body mass index were below the third percentile and he demonstrated loss of joint position and vibratory sense on examination. Laboratory studies revealed megaloblastic anaemia while an initial MRI of the brain showed no evidence of mass lesions or other abnormalities. A dietary history revealed the child subscribed to a restrictive vegan diet with little to no intake of animal products or other fortified foods. The child was diagnosed with presumed vitamin B12 deficiency and was treated with intramuscular B12 injections. Neurological symptoms resolved promptly within several days after starting therapy. This case underlines the importance of assessing nutritional status in the evaluation of neurological dysfunction in the pediatric patient.

  13. Placental polyp: a rare cause of iron deficiency anemia

    Directory of Open Access Journals (Sweden)

    Fernando Peixoto Ferraz de Campos

    2011-12-01

    Full Text Available Placental polyps are defined as pedunculated or polypoid fragments of placentaor ovular membranes retained for an indefinite period of time into the uterus afterabortion or child birth. An important cause of retention is placental accretism, anabnormal adherence of the placenta into the uterine wall. Chronic cases are rarelyreported in the literature. In these cases, the placental retention in the immediatepostpartum is not followed by heavy bleeding what makes the diagnosischallenging. We report a rare case of iron-deficiency anemia in a multiparous29-year-old female patient two years after the last delivery. She sought medicalcare with clinical symptoms of anemia and recent menses alterations. Therewas no history of abortion. On gynecological examination, there was a twofoldenlarged uterus, and the pelvic ultrasound revealed an image compatible with anendometrial polyp. She underwent open hysterectomy because of uncontrollablebleeding followed by hypotension after curettage. The histolopathologicexamination revealed a partially hyalinized and necrotic placental polyp.

  14. How common is vitamin B-12 deficiency?

    Science.gov (United States)

    Allen, Lindsay H

    2009-02-01

    In considering the vitamin B-12 fortification of flour, it is important to know who is at risk of vitamin B-12 deficiency and whether those individuals would benefit from flour fortification. This article reviews current knowledge of the prevalence and causes of vitamin B-12 deficiency and considers whether fortification would improve the status of deficient subgroups of the population. In large surveys in the United States and the United Kingdom, approximately 6% of those aged > or =60 y are vitamin B-12 deficient (plasma vitamin B-12 life. In developing countries, deficiency is much more common, starting in early life and persisting across the life span. Inadequate intake, due to low consumption of animal-source foods, is the main cause of low serum vitamin B-12 in younger adults and likely the main cause in poor populations worldwide; in most studies, serum vitamin B-12 concentration is correlated with intake of this vitamin. In older persons, food-bound cobalamin malabsorption becomes the predominant cause of deficiency, at least in part due to gastric atrophy, but it is likely that most elderly can absorb the vitamin from fortified food. Fortification of flour with vitamin B-12 is likely to improve the status of most persons with low stores of this vitamin. However, intervention studies are still needed to assess efficacy and functional benefits of increasing intake of the amounts likely to be consumed in flour, including in elderly persons with varying degrees of gastric atrophy.

  15. Dietary phytate, zinc and hidden zinc deficiency.

    Science.gov (United States)

    Sandstead, Harold H; Freeland-Graves, Jeanne H

    2014-10-01

    Epidemiological data suggest at least one in five humans are at risk of zinc deficiency. This is in large part because the phytate in cereals and legumes has not been removed during food preparation. Phytate, a potent indigestible ligand for zinc prevents it's absorption. Without knowledge of the frequency of consumption of foods rich in phytate, and foods rich in bioavailable zinc, the recognition of zinc deficiency early in the illness may be difficult. Plasma zinc is insensitive to early zinc deficiency. Serum ferritin concentration≤20μg/L is a potential indirect biomarker. Early effects of zinc deficiency are chemical, functional and may be "hidden". The clinical problem is illustrated by 2 studies that involved US Mexican-American children, and US premenopausal women. The children were consuming home diets that included traditional foods high in phytate. The premenopausal women were not eating red meat on a regular basis, and their consumption of phytate was mainly from bran breakfast cereals. In both studies the presence of zinc deficiency was proven by functional responses to controlled zinc treatment. In the children lean-mass, reasoning, and immunity were significantly affected. In the women memory, reasoning, and eye-hand coordination were significantly affected. A screening self-administered food frequency questionnaire for office might help caregiver's identify patients at risk of zinc deficiency. Copyright © 2014 Elsevier GmbH. All rights reserved.

  16. Glucose 6 phosphate dehydrogenase deficiency in adults

    International Nuclear Information System (INIS)

    Khan, M.

    2004-01-01

    Objective: To determine the frequency of glucose-6-phosphate dehydrogenase (G6PD) deficiency in adults presented with anemia. Subjects and Methods: Eighteen months admission data was reviewed for G6PD deficiency as a cause of anemia. Anemia was defined by world health organization (WHO) criteria as haemoglobin less than 11.3 gm%. G6PD activity was measured by Sigma dye decolorisation method. All patients were screened for complications of hemolysis and its possible cause. Patients with more than 13 years of age were included in the study. Results: Out of 3600 patients admitted, 1440 were found anaemic and 49 as G6PD deficient. So the frequency of G6PD deficiency in anaemic patients was 3.4% and the overall frequency is 1.36%. G6PD deficiency among males and females was three and six percent respectively. Antimalarials and antibiotics containing sulphonamide group were the most common precipitating factors for hemolysis. Anemia and jaundice were the most common presentations while malaria was the most common associated disease. Acute renal failure was the most severe complication occurring in five patients with two deaths. Conclusion: G6PD deficiency is a fairly common cause of anemia with medicine as common precipitating factor for hemolysis. Such complications can be avoided with early recognition of the disease and avoiding indiscriminate use of medicine. (author)

  17. MicroRNA-146a Deficiency Protects against Listeria monocytogenes Infection by Modulating the Gut Microbiota

    Directory of Open Access Journals (Sweden)

    Chong-Tao Du

    2018-03-01

    Full Text Available The gut microbiota and microRNAs play important roles in the defense against infection. However, the role of miR-146a in L. monocytogenes infection and gut microbiota remains unclear. We tried to determine whether miR-146a controlled L. monocytogenes infection by regulating the gut microbiota. Wild-type and miR-146a-deficient mice or macrophages were used to characterize the impact of miR-146a on animal survival, cell death, bacterial clearance, and gut microbiota following L. monocytogenes challenge. We found that L. monocytogenes infection induced miR-146a expression both in vitro and in vivo. When compared to wild-type mice, miR-146a-deficient mice were more resistant to L. monocytogenes infection. MiR-146a deficiency in macrophages resulted in reduced invasion and intracellular survival of L. monocytogenes. High-throughput sequencing of 16S rRNA revealed that the gut microbiota composition differed between miR-146a-deficient and wild-type mice. Relative to wild-type mice, miR-146a-deficient mice had decreased levels of the Proteobacteria phylum, Prevotellaceae family, and Parasutterella genus, and significantly increased short-chain fatty acid producing bacteria, including the genera Alistipes, Blautia, Coprococcus_1, and Ruminococcus_1. Wild-type mice co-housed with miR-146a-deficient mice had increased resistance to L. monocytogenes, indicating that miR-146a deficiency guides the gut microbiota to alleviate infection. Together, these results suggest that miR-146a deficiency protects against L. monocytogenes infection by regulating the gut microbiota.

  18. Adaptive gene regulation in the Striatum of RGS9-deficient mice.

    Directory of Open Access Journals (Sweden)

    Kathy Busse

    Full Text Available BACKGROUND: RGS9-deficient mice show drug-induced dyskinesia but normal locomotor activity under unchallenged conditions. RESULTS: Genes related to Ca2+ signaling and their functions were regulated in RGS9-deficient mice. CONCLUSION: Changes in Ca2+ signaling that compensate for RGS9 loss-of-function can explain the normal locomotor activity in RGS9-deficient mice under unchallenged conditions. SIGNIFICANCE: Identified signaling components may represent novel targets in antidyskinetic therapy. The long splice variant of the regulator of G-protein signaling 9 (RGS9-2 is enriched in striatal medium spiny neurons and dampens dopamine D2 receptor signaling. Lack of RGS9-2 can promote while its overexpression prevents drug-induced dyskinesia. Other animal models of drug-induced dyskinesia rather pointed towards overactivity of dopamine receptor-mediated signaling. To evaluate changes in signaling pathways mRNA expression levels were determined and compared in wild-type and RGS9-deficient mice. Unexpectedly, expression levels of dopamine receptors were unchanged in RGS9-deficient mice, while several genes related to Ca2+ signaling and long-term depression were differentially expressed when compared to wild type animals. Detailed investigations at the protein level revealed hyperphosphorylation of DARPP32 at Thr34 and of ERK1/2 in striata of RGS9-deficient mice. Whole cell patch clamp recordings showed that spontaneous synaptic events are increased (frequency and size in RGS9-deficient mice while long-term depression is reduced in acute brain slices. These changes are compatible with a Ca2+-induced potentiation of dopamine receptor signaling which may contribute to the drug-induced dyskinesia in RGS9-deficient mice.

  19. MicroRNA-146a Deficiency Protects against Listeria monocytogenes Infection by Modulating the Gut Microbiota.

    Science.gov (United States)

    Du, Chong-Tao; Gao, Wei; Ma, Ke; Yu, Shui-Xing; Li, Na; Yan, Shi-Qing; Zhou, Feng-Hua; Liu, Zhen-Zhen; Chen, Wei; Lei, Lian-Cheng; Yang, Yong-Jun; Han, Wen-Yu

    2018-03-26

    The gut microbiota and microRNAs play important roles in the defense against infection. However, the role of miR-146a in L. monocytogenes infection and gut microbiota remains unclear. We tried to determine whether miR-146a controlled L. monocytogenes infection by regulating the gut microbiota. Wild-type and miR-146a-deficient mice or macrophages were used to characterize the impact of miR-146a on animal survival, cell death, bacterial clearance, and gut microbiota following L. monocytogenes challenge. We found that L. monocytogenes infection induced miR-146a expression both in vitro and in vivo. When compared to wild-type mice, miR-146a-deficient mice were more resistant to L. monocytogenes infection. MiR-146a deficiency in macrophages resulted in reduced invasion and intracellular survival of L. monocytogenes . High-throughput sequencing of 16S rRNA revealed that the gut microbiota composition differed between miR-146a-deficient and wild-type mice. Relative to wild-type mice, miR-146a-deficient mice had decreased levels of the Proteobacteria phylum, Prevotellaceae family, and Parasutterella genus, and significantly increased short-chain fatty acid producing bacteria, including the genera Alistipes , Blautia , Coprococcus_1, and Ruminococcus_1 . Wild-type mice co-housed with miR-146a-deficient mice had increased resistance to L. monocytogenes , indicating that miR-146a deficiency guides the gut microbiota to alleviate infection. Together, these results suggest that miR-146a deficiency protects against L. monocytogenes infection by regulating the gut microbiota.

  20. Deficiency of Carbonic Anhydrase II Results in a Urinary Concentrating Defect

    Directory of Open Access Journals (Sweden)

    Devishree Krishnan

    2018-01-01

    Full Text Available Carbonic anhydrase II (CAII is expressed along the nephron where it interacts with a number of transport proteins augmenting their activity. Aquaporin-1 (AQP1 interacts with CAII to increase water flux through the water channel. Both CAII and aquaporin-1 are expressed in the thin descending limb (TDL; however, the physiological role of a CAII-AQP1 interaction in this nephron segment is not known. To determine if CAII was required for urinary concentration, we studied water handling in CAII-deficient mice. CAII-deficient mice demonstrate polyuria and polydipsia as well as an alkaline urine and bicarbonaturia, consistent with a type III renal tubular acidosis. Natriuresis and hypercalciuria cause polyuria, however, CAII-deficient mice did not have increased urinary sodium nor calcium excretion. Further examination revealed dilute urine in the CAII-deficient mice. Urinary concentration remained reduced in CAII-deficient mice relative to wild-type animals even after water deprivation. The renal expression and localization by light microscopy of NKCC2 and aquaporin-2 was not altered. However, CAII-deficient mice had increased renal AQP1 expression. CAII associates with and increases water flux through aquaporin-1. Water flux through aquaporin-1 in the TDL of the loop of Henle is essential to the concentration of urine, as this is required to generate a concentrated medullary interstitium. We therefore measured cortical and medullary interstitial concentration in wild-type and CAII-deficient mice. Mice lacking CAII had equivalent cortical interstitial osmolarity to wild-type mice: however, they had reduced medullary interstitial osmolarity. We propose therefore that reduced water flux through aquaporin-1 in the TDL in the absence of CAII prevents the generation of a maximally concentrated medullary interstitium. This, in turn, limits urinary concentration in CAII deficient mice.

  1. PPARgamma Deficiency Counteracts Thymic Senescence

    Directory of Open Access Journals (Sweden)

    David Ernszt

    2017-11-01

    Full Text Available Thymic senescence contributes to increased incidence of infection, cancer and autoimmunity at senior ages. This process manifests as adipose involution. As with other adipose tissues, thymic adipose involution is also controlled by PPARgamma. This is supported by observations reporting that systemic PPARgamma activation accelerates thymic adipose involution. Therefore, we hypothesized that decreased PPARgamma activity could prevent thymic adipose involution, although it may trigger metabolic adverse effects. We have confirmed that both human and murine thymic sections show marked staining for PPARgamma at senior ages. We have also tested the thymic lobes of PPARgamma haplo-insufficient and null mice. Supporting our working hypothesis both adult PPARgamma haplo-insufficient and null mice show delayed thymic senescence by thymus histology, thymocyte mouse T-cell recombination excision circle qPCR and peripheral blood naive T-cell ratio by flow-cytometry. Delayed senescence showed dose–response with respect to PPARgamma deficiency. Functional immune parameters were also evaluated at senior ages in PPARgamma haplo-insufficient mice (null mice do not reach senior ages due to metabolic adverse affects. As expected, sustained and elevated T-cell production conferred oral tolerance and enhanced vaccination efficiency in senior PPARgamma haplo-insufficient, but not in senior wild-type littermates according to ELISA IgG measurements. Of note, humans also show increased oral intolerance issues and decreased protection by vaccines at senior ages. Moreover, PPARgamma haplo-insufficiency also exists in human known as a rare disease (FPLD3 causing metabolic adverse effects, similar to the mouse. When compared to age- and metabolic disorder-matched other patient samples (FPLD2 not affecting PPARgamma activity, FPLD3 patients showed increased human Trec (hTrec values by qPCR (within healthy human range suggesting delayed thymic senescence, in accordance with

  2. Vitamin D Deficiency in Patients with Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    Suzan M. Attar

    2013-01-01

    Full Text Available Objectives: Hypovitaminosis D is common in the general population. Many studies that have been conducted to show the association between vitamin D deficiency and systemic lupus erythematosus (SLE reveal that deficiencies in vitamin D are common in this group of patients. Our aim was to study the relationship between 25(OHD and disease activity in patients with SLE.Methods: Retrospective cohort study of patients with SLE who were followed up at King Abdulaziz University Hospital, Jeddah, from January 2007 to November 2010. Demographic and clinical data were recorded and the 25(OHD levels of the patients were measured. Chi square tests, Student’s t-test, ANOVA and Pearson tests were used for data analysis. ANOVA test was followed by Bonferroni correction. A p-value <0.05 was considered significant.Results: Ninety-five patients with SLE were enrolled in the study. The levels of 25(OHD were significantly lower in patients with active SLE (n=41; 43% than in those with inactive disease (n=54; 57%; p=0.04. The mean (SD levels were 22.3 (14 nmol/L for patients with active disease against 25.0 (14 nmol/L for patients with inactive SLE. No correlation was detected between 25(OH D levels and disease activity score evaluated by SLEDAI-2K. By Pearson correlation, a significant negative correlation existed between 25(OH D and anti ds-DNA (r=-0.38; p<0.001; a positive correlation existed between 25(OHD levels and C4 (r=0.25; p=0.25. By chi square testing, azathioprine treatment (OR=3.5, low C4 (OR= 2.23, low C3 (OR=1.92, and active disease (OR=1.6 were associated with 25(OHD deficiency in SLE patients.Conclusion: Vitamin D deficiency is frequent in patients with SLE. Patients with SLE have a higher risk of developing 25(OHD deficiency in the presence of low serum C3 and C4 levels, and high anti-dsDNA levels.

  3. Evidence Report: Risk of Performance Errors Due to Training Deficiencies

    Science.gov (United States)

    Barshi, Immanuel; Dempsey, Donna L.

    2016-01-01

    Substantial evidence supports the claim that inadequate training leads to performance errors. Barshi and Loukopoulos (2012) demonstrate that even a task as carefully developed and refined over many years as operating an aircraft can be significantly improved by a systematic analysis, followed by improved procedures and improved training (see also Loukopoulos, Dismukes, & Barshi, 2009a). Unfortunately, such a systematic analysis of training needs rarely occurs during the preliminary design phase, when modifications are most feasible. Training is often seen as a way to compensate for deficiencies in task and system design, which in turn increases the training load. As a result, task performance often suffers, and with it, the operators suffer and so does the mission. On the other hand, effective training can indeed compensate for such design deficiencies, and can even go beyond to compensate for failures of our imagination to anticipate all that might be needed when we send our crew members to go where no one else has gone before. Much of the research literature on training is motivated by current training practices aimed at current training needs. Although there is some experience with operations in extreme environments on Earth, there is no experience with long-duration space missions where crews must practice semi-autonomous operations, where ground support must accommodate significant communication delays, and where so little is known about the environment. Thus, we must develop robust methodologies and tools to prepare our crews for the unknown. The research necessary to support such an endeavor does not currently exist, but existing research does reveal general challenges that are relevant to long-duration, high-autonomy missions. The evidence presented here describes issues related to the risk of performance errors due to training deficiencies. Contributing factors regarding training deficiencies may pertain to organizational process and training programs for

  4. Rapid and Complete Reversal of Sensory Ataxia by Gene Therapy in a Novel Model of Friedreich Ataxia.

    Science.gov (United States)

    Piguet, Françoise; de Montigny, Charline; Vaucamps, Nadège; Reutenauer, Laurence; Eisenmann, Aurélie; Puccio, Hélène

    2018-05-28

    Friedreich ataxia (FA) is a rare mitochondrial disease characterized by sensory and spinocerebellar ataxia, hypertrophic cardiomyopathy, and diabetes, for which there is no treatment. FA is caused by reduced levels of frataxin (FXN), an essential mitochondrial protein involved in the biosynthesis of iron-sulfur (Fe-S) clusters. Despite significant progress in recent years, to date, there are no good models to explore and test therapeutic approaches to stop or reverse the ganglionopathy and the sensory neuropathy associated to frataxin deficiency. Here, we report a new conditional mouse model with complete frataxin deletion in parvalbumin-positive cells that recapitulate the sensory ataxia and neuropathy associated to FA, albeit with a more rapid and severe course. Interestingly, although fully dysfunctional, proprioceptive neurons can survive for many weeks without frataxin. Furthermore, we demonstrate that post-symptomatic delivery of frataxin-expressing AAV allows for rapid and complete rescue of the sensory neuropathy associated with frataxin deficiency, thus establishing the pre-clinical proof of concept for the potential of gene therapy in treating FA neuropathy. Copyright © 2018 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

  5. Iron deficiency anaemia among apparently healthy pre-school ...

    African Journals Online (AJOL)

    Background: Iron deficiency, and specifically iron deficiency anaemia, remains one of the most severe and important nutritional deficiencies in the world today. Objective: To estimate the prevalence and associated factors for iron deficiency anaemia among pre-school children in Lagos. Methodology: The study was ...

  6. In HepG2 cells, coexisting carnitine deficiency masks important indicators of marginal biotin deficiency.

    Science.gov (United States)

    Bogusiewicz, Anna; Boysen, Gunnar; Mock, Donald M

    2015-01-01

    A large number of birth defects are related to nutrient deficiencies; concern that biotin deficiency is teratogenic in humans is reasonable. Surprisingly, studies indicate that increased urinary 3-hydroxyisovalerylcarnitine (3HIAc), a previously validated marker of biotin deficiency, is not a valid biomarker in pregnancy. In this study we hypothesized that coexisting carnitine deficiency can prevent the increase in 3HIAc due to biotin deficiency. We used a 2-factor nutrient depletion design to induce isolated and combined biotin and carnitine deficiency in HepG2 cells and then repleted cells with carnitine. To elucidate the metabolic pathogenesis, we quantitated intracellular and extracellular free carnitine, acylcarnitines, and acylcarnitine ratios using liquid chromatography-tandem mass spectrometry. Relative to biotin-sufficient, carnitine-sufficient cells, intracellular acetylcarnitine increased by 90%, propionylcarnitine more than doubled, and 3HIAc increased by >10-fold in biotin-deficient, carnitine-sufficient (BDCS) cells, consistent with a defensive mechanism in which biotin-deficient cells transesterify the acyl-coenzyme A (acyl-CoA) substrates of the biotin-dependent carboxylases to the related acylcarnitines. Likewise, in BDCS cells, the ratio of acetylcarnitine to malonylcarnitine and the ratio of propionylcarnitine to methylmalonylcarnitine both more than tripled, and the ratio of 3HIAc to 3-methylglutarylcarnitine (MGc) increased by >10-fold. In biotin-deficient, carnitine-deficient (BDCD) cells, the 3 substrate-derived acylcarnitines changed little, but the substrate:product ratios were masked to a lesser extent. Moreover, carnitine repletion unmasked biotin deficiency in BDCD cells as shown by increases in acetylcarnitine, propionylcarnitine, and 3HIAc (each increased by >50-fold). Likewise, ratios of acetylcarnitine:malonylcarnitine, propionylcarnitine:methylmalonylcarnitine, and 3HIAc:MGc all increased by >8-fold. Our findings provide strong

  7. Sleep transitions in hypocretin-deficient narcolepsy.

    Science.gov (United States)

    Sorensen, Gertrud Laura; Knudsen, Stine; Jennum, Poul

    2013-08-01

    Narcolepsy is characterized by instability of sleep-wake, tonus, and rapid eye movement (REM) sleep regulation. It is associated with severe hypothalamic hypocretin deficiency, especially in patients with cataplexy (loss of tonus). As the hypocretin neurons coordinate and stabilize the brain's sleep-wake pattern, tonus, and REM flip-flop neuronal centers in animal models, we set out to determine whether hypocretin deficiency and/or cataplexy predicts the unstable sleep-wake and REM sleep pattern of the human phenotype. We measured the frequency of transitions in patients with narcolepsy between sleep-wake states and to/from REM and NREM sleep stages. Patients were subdivided by the presence of +/- cataplexy and +/- hypocretin-1 deficiency. Sleep laboratory studies conducted from 2001-2011. In total 63 narcolepsy patients were included in the study. Cataplexy was present in 43 of 63 patients and hypocretin-1 deficiency was present in 37 of 57 patients. Hypocretin-deficient patients with narcolepsy had a significantly higher frequency of sleep-wake transitions (P = 0.014) and of transitions to/from REM sleep (P = 0.044) than patients with normal levels of hypocretin-1. Patients with cataplexy had a significantly higher frequency of sleep-wake transitions (P = 0.002) than those without cataplexy. A multivariate analysis showed that transitions to/from REM sleep were predicted mainly by hypocretin-1 deficiency (P = 0.011), whereas sleep-wake transitions were predicted mainly by cataplexy (P = 0.001). In human narcolepsy, hypocretin deficiency and cataplexy are both associated with signs of destabilized sleep-wake and REM sleep control, indicating that the disorder may serve as a human model for the sleep-wake and REM sleep flip-flop switches.

  8. Glucose-6-Phosphate Dehydrogenase Deficiency and Adrenal Hemorrhage in a Filipino Neonate with Hyperbilirubinemia

    Directory of Open Access Journals (Sweden)

    Akira Ohishi

    2013-05-01

    Full Text Available We report on a Filipino neonate with early onset and prolonged hyperbilirubinemia who was delivered by a vacuum extraction due to a prolonged labor. Subsequent studies revealed adrenal hemorrhage and glucose-6-phosphate dehydrogenase (G6PD deficiency. It is likely that asphyxia and resultant hypoxia underlie the occurrence of adrenal hemorrhage and the clinical manifestation of G6PD deficiency and that the presence of the two events explains the early onset and prolonged hyperbilirubinemia of this neonate. Our results represent the importance of examining possible underlying factors for the development of severe, early onset, or prolonged hyperbilirubinemia.

  9. Iron deficiency anemia from diagnosis to treatment in children

    OpenAIRE

    Özdemir, Nihal

    2015-01-01

    Iron deficiency is the most common nutritional deficiency worldwide and an important public health problem especially in developing countries. Since the most important indicator of iron deficieny is anemia, the terms “iron deficiency” and “iron deficiency anemia” are often used interchangeably. However, iron deficiency may develop in the absence of anemia and the tissues may be affected from this condition. The most common causes of iron deficiency in children include insufficient intake toge...

  10. Zinc Deficiency in Humans and its Amelioration

    Directory of Open Access Journals (Sweden)

    Yashbir Singh Shivay

    2015-01-01

    Full Text Available Zinc (Zn deficiency in humans has recently received considerable attention. Global mortality in children under 5 years of age in 2004 due to Zn deficiency was estimated at 4,53,207 as against 6,66,771 for vitamin A deficiency; 20,854 for iron deficiency and 3,619 for iodine deficiency. In humans 2800-3000 proteins contain Zn prosthetic group and Zn is an integral component of zinc finger prints that regulate DNA transcription. Zinc is a Type-2 nutrient, which means that its concentration in blood does not decrease in proportion of the Zn deficiency. Adverse effects of Zn deficiency vary with age: low weight gain, diarrhoea, aneroxia and neurobehavioral disturbances are observed in infants, while skin changes and dwarfism are frequent in toddlers and adolescents. Common manifestations of Zn deficiency among elderly include hypogeusia, chronic non-healing ulcers and recurrent infections.Ameliorative measures of Zn deficiency in humans can be classified in two groups, namely, nutraceutical and biofortification of food grains. Nutraceutical interventions include pharmaceutical supplements, dietary supplements and dietary diversification, while biofortification of food grains can be achieved by genetic modification (GM of crops or by agronomic techniques that include soil or/and foliar fertilization of crops.The major disadvantage of nutraceutical approaches is that the major beneficiaries are urban people and the poor rural masses that need adequate Zn nutrition most are left out. Genetic biofortification of food grains requires large amounts of funds and a fairly long-period of time. Further, a large number of countries have not yet accepted genetically modified (GM foods. On the other hand agronomic biofortification of food grains yields immediate effects and rural and urban people are equally benefitted. Our studies have shown that Zn concentration in cereals (rice, wheat etc and pulses can be considerably increased by soil or/and foliar

  11. Vitamin D Deficiency Among Professional Basketball Players.

    Science.gov (United States)

    Fishman, Matthew P; Lombardo, Stephen J; Kharrazi, F Daniel

    2016-07-01

    Vitamin D plays an important role in several systems of the human body. Various studies have linked vitamin D deficiency to stress and insufficiency fractures, muscle recovery and function, and athletic performance. The prevalence of vitamin D deficiency in the elite athletic population has not been extensively studied, and very few reports exist among professional athletes. There is a high prevalence of vitamin D deficiency or insufficiency among players attending the National Basketball Association (NBA) Combine. Cross-sectional study; Level of evidence, 3. This is a retrospective review of data previously collected as part of the routine medical evaluation of players in the NBA Combines from 2009 through 2013. Player parameters evaluated were height, weight, body mass index (BMI), and vitamin D level. Statistical analysis using t tests and analysis of variance was used to detect any correlation between the player parameters and vitamin D level. Vitamin D levels were categorized as deficient (32 ng/mL). After institutional review board approval was submitted to the NBA, the NBA released deidentified data on 279 players who participated in the combines from 2009 through 2013. There were 90 players (32.3%) who were deficient, 131 players (47.0%) who were insufficient, and 58 players (20.8%) who were sufficient. A total of 221 players (79.3%) were either vitamin D deficient or insufficient. Among all players included, the average vitamin D level was 25.6 ± 10.2 ng/mL. Among the players who were deficient, insufficient, and sufficient, the average vitamin D levels were 16.1 ± 2.1 ng/mL, 25.0 ± 3.4 ng/mL, and 41.6 ± 8.6 ng/mL, respectively. Player height and weight were significantly increased in vitamin D-sufficient players compared with players who were not sufficient (P = .0008 and .009, respectively). Player age and BMI did not significantly differ depending on vitamin D status (P = .15 and .77, respectively). There is a high prevalence of vitamin D deficiency

  12. Zinc Deficiency in Humans and its Amelioration

    Directory of Open Access Journals (Sweden)

    Yashbir Singh Shivay

    2015-12-01

    Full Text Available Zinc (Zn deficiency in humans has recently received considerable attention. Global mortality in children under 5 years of age in 2004 due to Zn deficiency was estimated at 4,53,207 as against 6,66,771 for vitamin A deficiency; 20,854 for iron deficiency and 3,619 for iodine deficiency. In humans 2800-3000 proteins contain Zn prosthetic group and Zn is an integral component of zinc finger prints that regulate DNA transcription. Zinc is a Type-2 nutrient, which means that its concentration in blood does not decrease in proportion of the Zn deficiency. Adverse effects of Zn deficiency vary with age: low weight gain, diarrhoea, aneroxia and neurobehavioral disturbances are observed in infants, while skin changes and dwarfism are frequent in toddlers and adolescents. Common manifestations of Zn deficiency among elderly include hypogeusia, chronic non-healing ulcers and recurrent infections. Ameliorative measures of Zn deficiency in humans can be classified in two groups, namely, nutraceutical and biofortification of food grains. Nutraceutical interventions include pharmaceutical supplements, dietary supplements and dietary diversification, while biofortification of food grains can be achieved by genetic modification (GM of crops or by agronomic techniques that include soil or/and foliar fertilization of crops. The major disadvantage of nutraceutical approaches is that the major beneficiaries are urban people and the poor rural masses that need adequate Zn nutrition most are left out. Genetic biofortification of food grains requires large amounts of funds and a fairly long-period of time. Further, a large number of countries have not yet accepted genetically modified (GM foods. On the other hand agronomic biofortification of food grains yields immediate effects and rural and urban people are equally benefitted. Our studies have shown that Zn concentration in cereals (rice, wheat etc and pulses can be considerably increased by soil or/and foliar

  13. Clinical implications of vitamin D deficiency

    Directory of Open Access Journals (Sweden)

    Beata Matyjaszek-Matuszek

    2015-06-01

    Full Text Available Vitamin D deficiency is a common medical problem worldwide and its prevalence rises along with latitude, obesity, sedentary lifestyle, limited sunlight exposure and aging. A great body of evidence has shown that patients with vitamin D deficiency have increased cardiovascular risks and total mortality. Conversely, the presence of comorbidities progressive with age such as abdominal obesity, insulin resistance, type 2 diabetes and hypertension places the patients at an increased risk of vitamin D deficiency. The multidirectional effect of vitamin D deficiency is present in different phases of the aging process. Based on the literature review, the risk factors for vitamin D insufficiency most often found in post-menopausal women include limited sun exposure and time spent outdoors, inadequate dietary vitamin D intake, winter season and increased age. Vitamin D supplementation in this group might offer prevention of falls and fractures and may be beneficial for cardiovascular health, what may be especially important in osteoporotic and elderly populations. Prevention and treatment processes involve education regarding sunlight exposure and pharmacological cholecalciferol supplementation according to the recommendations for Central Europe. This manuscript reviews the role of vitamin D and its deficiency and considers their clinical implications, with particular regard to peri- and postmenopausal women.

  14. Biochemical Assessment of Coenzyme Q10 Deficiency

    Directory of Open Access Journals (Sweden)

    Juan Carlos Rodríguez-Aguilera

    2017-03-01

    Full Text Available Coenzyme Q10 (CoQ10 deficiency syndrome includes clinically heterogeneous mitochondrial diseases that show a variety of severe and debilitating symptoms. A multiprotein complex encoded by nuclear genes carries out CoQ10 biosynthesis. Mutations in any of these genes are responsible for the primary CoQ10 deficiency, but there are also different conditions that induce secondary CoQ10 deficiency including mitochondrial DNA (mtDNA depletion and mutations in genes involved in the fatty acid β-oxidation pathway. The diagnosis of CoQ10 deficiencies is determined by the decrease of its content in skeletal muscle and/or dermal skin fibroblasts. Dietary CoQ10 supplementation is the only available treatment for these deficiencies that require a rapid and distinct diagnosis. Here we review methods for determining CoQ10 content by HPLC separation and identification using alternative approaches including electrochemical detection and mass spectrometry. Also, we review procedures to determine the CoQ10 biosynthesis rate using labeled precursors.

  15. Thyroid disorders in mild iodine deficiency.

    Science.gov (United States)

    Laurberg, P; Nøhr, S B; Pedersen, K M; Hreidarsson, A B; Andersen, S; Bülow Pedersen, I; Knudsen, N; Perrild, H; Jørgensen, T; Ovesen, L

    2000-11-01

    Comparative epidemiologic studies in areas with low and high iodine intake and controlled studies of iodine supplementation have demonstrated that the major consequence of mild-to-moderate iodine deficiency for the health of the population is an extraordinarily high occurrence of hyperthyroidism in elderly subjects, especially women, with risk of cardiac arrhythmias, osteoporosis, and muscle wasting. The hyperthyroidism is caused by autonomous nodular growth and function of the thyroid gland and it is accompanied by a high frequency of goiter. Pregnant women and small children are not immediately endangered but the consequences of severe iodine deficiency for brain development are grave and a considerable safety margin is advisable. Moreover, a shift toward less malignant types of thyroid cancer and a lower radiation dose to the thyroid in case of nuclear fallout support that mild-to-moderate iodine deficiency should be corrected. However, there is evidence that a high iodine intake may be associated with more autoimmune hypothyroidism, and that Graves' disease may manifest at a younger age and be more difficult to treat. Hence, the iodine intake should be brought to a level at which iodine deficiency disorders are avoided but not higher. Iodine supplementation programs should aim at relatively uniform iodine intake, avoiding deficient or excessive iodine intake in subpopulations. To adopt such a strategy, surveillance programs are needed.

  16. A mutational signature reveals alterations underlying deficient homologous recombination repair in breast cancer.

    Science.gov (United States)

    Polak, Paz; Kim, Jaegil; Braunstein, Lior Z; Karlic, Rosa; Haradhavala, Nicholas J; Tiao, Grace; Rosebrock, Daniel; Livitz, Dimitri; Kübler, Kirsten; Mouw, Kent W; Kamburov, Atanas; Maruvka, Yosef E; Leshchiner, Ignaty; Lander, Eric S; Golub, Todd R; Zick, Aviad; Orthwein, Alexandre; Lawrence, Michael S; Batra, Rajbir N; Caldas, Carlos; Haber, Daniel A; Laird, Peter W; Shen, Hui; Ellisen, Leif W; D'Andrea, Alan D; Chanock, Stephen J; Foulkes, William D; Getz, Gad

    2017-10-01

    Biallelic inactivation of BRCA1 or BRCA2 is associated with a pattern of genome-wide mutations known as signature 3. By analyzing ∼1,000 breast cancer samples, we confirmed this association and established that germline nonsense and frameshift variants in PALB2, but not in ATM or CHEK2, can also give rise to the same signature. We were able to accurately classify missense BRCA1 or BRCA2 variants known to impair homologous recombination (HR) on the basis of this signature. Finally, we show that epigenetic silencing of RAD51C and BRCA1 by promoter methylation is strongly associated with signature 3 and, in our data set, was highly enriched in basal-like breast cancers in young individuals of African descent.

  17. Preclinical antivenom-efficacy testing reveals potentially disturbing deficiencies of snakebite treatment capability in East Africa.

    Directory of Open Access Journals (Sweden)

    Robert A Harrison

    2017-10-01

    Full Text Available Antivenom is the treatment of choice for snakebite, which annually kills an estimated 32,000 people in sub-Saharan Africa and leaves approximately 100,000 survivors with permanent physical disabilities that exert a considerable socioeconomic burden. Over the past two decades, the high costs of the most polyspecifically-effective antivenoms have sequentially reduced demand, commercial manufacturing incentives and production volumes that have combined to create a continent-wide vacuum of effective snakebite therapy. This was quickly filled with new, less expensive antivenoms, many of which are of untested efficacy. Some of these successfully marketed antivenoms for Africa are inappropriately manufactured with venoms from non-African snakes and are dangerously ineffective. The uncertain efficacy of available antivenoms exacerbates the complexity of designing intervention measures to reduce the burden of snakebite in sub-Saharan Africa. The objective of this study was to preclinically determine the ability of antivenoms available in Kenya to neutralise the lethal effects of venoms from the most medically important snakes in East Africa.We collected venom samples from the most medically important snakes in East Africa and determined their toxicity in a mouse model. Using a 'gold standard' comparison protocol, we preclinically tested the comparative venom-neutralising efficacy of four antivenoms available in Kenya with two antivenoms of clinically-proven efficacy. To explain the variant efficacies of these antivenoms we tested the IgG-venom binding characteristics of each antivenom using in vitro IgG titre, avidity and venom-protein specificity assays. We also measured the IgG concentration of each antivenom.None of the six antivenoms are preclinically effective, at the doses tested, against all of the most medically important snakes of the region. The very limited snake polyspecific efficacy of two locally available antivenoms is of concern. In vitro assays of the abilities of 'test' antivenom IgGs to bind venom proteins were not substantially different from that of the 'gold standard' antivenoms. The least effective antivenoms had the lowest IgG content/vial.Manufacture-stated preclinical efficacy statements guide decision making by physicians and antivenom purchasers in sub-Saharan Africa. This is because of the lack of both clinical data on the efficacy of most of the many antivenoms used to treat patients and independent preclinical assessment. Our preclinical efficacy assessment of antivenoms available in Kenya identifies important limitations for two of the most commonly-used antivenoms, and that no antivenom is preclinically effective against all the regionally important snakes. The potential implication to snakebite treatment is of serious concern in Kenya and elsewhere in sub-Saharan Africa, and underscores the dilemma physicians face, the need for clinical data on antivenom efficacy and the medical and societal value of establishing independent preclinical antivenom-efficacy testing facilities throughout the continent.

  18. Burn injury reveals altered phenotype in mannan-binding lectin-deficient mice

    DEFF Research Database (Denmark)

    Møller-Kristensen, Mette; Hamblin, Michael R; Thiel, Steffen

    2007-01-01

    Burn injury destroys skin, the second largest innate immune organ in the body, and triggers chaotic immune and inflammatory responses. The pattern recognition molecule, mannan-binding lectin (MBL), plays an important role in the first-line host defense against infectious agents. MBL initiates...... the lectin complement pathway and acts as an opsonin. Recent studies suggest that MBL also modulates inflammatory responses. We report that local responses after burn in MBL null mice differ from those found in wild-type (WT) mice in the following important biological markers: spontaneous eschar separation......, thinned epidermis and dermis, upregulation of soluble factors including cytokines, chemokines, cell adhesion molecules, a growth factor-binding protein, and matrix metalloproteinases. Mice lacking C1q, C4, or C3 did not show the lack of eschar separation seen in MBL null-burn phenotype. These findings...

  19. Deficiency of α-1-antitrypsin influences systemic iron homeostasis

    Directory of Open Access Journals (Sweden)

    Ghio AJ

    2013-01-01

    Full Text Available Andrew J Ghio,1 Joleen M Soukup,1 Judy H Richards,1 Bernard M Fischer,2 Judith A Voynow,2 Donald E Schmechel31US Environmental Protection Agency, Chapel Hill, NC, USA; 2Division of Pediatric Pulmonary Medicine, Department of Pediatrics,3Joseph and Kathleen Bryan Alzheimer Disease Research Center, Department of Medicine (Neurology, Duke University Medical Center, Durham, NC, USAAbstract: There is evidence that proteases and antiproteases participate in the iron homeostasis of cells and living systems. We tested the postulate that α-1 antitrypsin (A1AT polymorphism and the consequent deficiency of this antiprotease in humans are associated with a systemic disruption in iron homeostasis. Archived plasma samples from Alpha-1 Foundation (30 MM, 30 MZ, and 30 ZZ individuals were analyzed for A1AT, ferritin, transferrin, and C-reactive protein (CRP. Plasma samples were also assayed for metals using inductively coupled plasma atomic emission spectroscopy (ICPAES. Plasma levels of A1AT in MZ and ZZ individuals were approximately 60% and 20% of those for MM individuals respectively. Plasma ferritin concentrations in those with the ZZ genotype were greater relative to those individuals with either MM or MZ genotype. Plasma transferrin for MM, MZ, and ZZ genotypes showed no significant differences. Linear regression analysis revealed a significant (negative relationship between plasma concentrations of A1AT and ferritin while that between A1AT and transferrin levels was not significant. Plasma CRP concentrations were not significantly different between MM, MZ, and ZZ individuals. ICPAES measurement of metals confirmed elevated plasma concentrations of nonheme iron among ZZ individuals. Nonheme iron concentrations correlated (negatively with levels of A1AT. A1AT deficiency is associated with evidence of a disruption in iron homeostasis with plasma ferritin and nonheme iron concentrations being elevated among those with the ZZ genotype.Keywords: α-1

  20. Empty sella syndrome associated with hormone deficiency in adults

    International Nuclear Information System (INIS)

    Oleaga, L.; Paja, M.; Goni, F.; Grande, J.; Grande, D.; Merino, M.; Delgado, A.

    1999-01-01

    The objective of this study was to correlate the magnetic resonance (MR) images in patients with hormone deficiencies with the clinical data and the hormonal status. We studied 11 cases ef empty sella with different peripheral pituitary deficiencies. Hormone levels were determined according to standard laboratory methods. All the patients underwent MR imaging. The studies were carried out with a 1 Tesla superconducting magnet, using the cranial cavity for transmission and reception. Segittal and coronal T1-weighted spin-echo sequences (TR/TE: 600/15 ms), axial T2-weighted spin-echo sequences (TR/TE: 3,500/19/93 ms) and gadolinium-enhanced (=.2 cc/kg body weight) sagital and coronal T1-weighted spin-echo sequences (TR/TE: 600/15 ms) were employed. Six of the patients presented partial or total hypopituitarism associated with the syndrome of inappropriate antidiuretic hormone secretion (SIADH); there was one case of panhypopituitarism without SIADH and four cases of primary hypothyroidism, there of which were associated with pituitary deficiency, MR imaging revealed five cases of partially empty sella with residual pituitary gland on the sella floor and six cases in which the sella was completely empty. This study also identified six cases of normally situated neurohypophysis, another four in which the neurohypophysis could not be identified and one case of ectopic neurohypophysis. MR imaging is the technique of choice in the study of abnormal hypothalamic-pituitary activity. Empty and partially empty sella should be included among the frequent causes of hypopituitarism, although there is no clear relationship between the degree of adenohypophyseal insufficiency and the degree of atrophy of this system as viewed in MR images. In some cases, this entity may be the radiological sign of a phase in the development of an autoimmune inflammatory process involving the pituitary gland. (Author) 16 refs

  1. Remodeling of Sensorimotor Brain Connectivity in Gpr88-Deficient Mice.

    Science.gov (United States)

    Arefin, Tanzil Mahmud; Mechling, Anna E; Meirsman, Aura Carole; Bienert, Thomas; Hübner, Neele Saskia; Lee, Hsu-Lei; Ben Hamida, Sami; Ehrlich, Aliza; Roquet, Dan; Hennig, Jürgen; von Elverfeldt, Dominik; Kieffer, Brigitte Lina; Harsan, Laura-Adela

    2017-10-01

    Recent studies have demonstrated that orchestrated gene activity and expression support synchronous activity of brain networks. However, there is a paucity of information on the consequences of single gene function on overall brain functional organization and connectivity and how this translates at the behavioral level. In this study, we combined mouse mutagenesis with functional and structural magnetic resonance imaging (MRI) to determine whether targeted inactivation of a single gene would modify whole-brain connectivity in live animals. The targeted gene encodes GPR88 (G protein-coupled receptor 88), an orphan G protein-coupled receptor enriched in the striatum and previously linked to behavioral traits relevant to neuropsychiatric disorders. Connectivity analysis of Gpr88-deficient mice revealed extensive remodeling of intracortical and cortico-subcortical networks. Most prominent modifications were observed at the level of retrosplenial cortex connectivity, central to the default mode network (DMN) whose alteration is considered a hallmark of many psychiatric conditions. Next, somatosensory and motor cortical networks were most affected. These modifications directly relate to sensorimotor gating deficiency reported in mutant animals and also likely underlie their hyperactivity phenotype. Finally, we identified alterations within hippocampal and dorsal striatum functional connectivity, most relevant to a specific learning deficit that we previously reported in Gpr88 -/- animals. In addition, amygdala connectivity with cortex and striatum was weakened, perhaps underlying the risk-taking behavior of these animals. This is the first evidence demonstrating that GPR88 activity shapes the mouse brain functional and structural connectome. The concordance between connectivity alterations and behavior deficits observed in Gpr88-deficient mice suggests a role for GPR88 in brain communication.

  2. Risk Factors of Development of Iron-Deficiency Conditions in Moscow Adolescents

    Directory of Open Access Journals (Sweden)

    I. N. Zakharova

    2015-01-01

    Full Text Available The article presents data on prevalence structure and causes of iron-deficiency conditions (IDC in adolescents. The authors describe both literature data and the findings of their own study in the adolescents (n = 337 studying at Moscow comprehensive schools. Iron- deficiency anemia was revealed in 5.3% of the examined adolescents, latent iron deficiency — in 17%; vast majority of the last were females. The authors also determined the most common causes of IDC development in adolescents: growth spurt (according to the anamnesis, a source of chronic blood loss (prolonged and abundant menstruations [in girls], frequent nasal bleeding, vegetarianism, intense physical activity, diet compliance, excess weight, and obesity. 

  3. Dysfunctional C8 beta chain in patients with C8 deficiency.

    Science.gov (United States)

    Tschopp, J; Penea, F; Schifferli, J; Späth, P

    1986-12-01

    Two sera from unrelated individuals, each lacking C8 activity, were examined by Western blot analysis. Using antisera raised against whole C8, the two sera are shown to lack the C8 beta chain, indicating a C8 beta deficiency, which is frequently observed in cases of dysfunctional C8. In contrast, by means of a specific anti-C8-beta antiserum, a C8 beta-like polypeptide chain of apparently identical molecular weight compared to normal C8 beta was detected. Digestion of normal and dysfunctional C8 beta with Staphylococcus aureus V8 protease revealed distinct differences in the enzymatic digestion pattern. We conclude that the dysfunction in the C8 protein in these two patients resides in the dysfunctional C8 beta chain, and that this form of C8 deficiency is distinct from C8 deficiencies previously reported, in which one or both C8 subunits are lacking.

  4. Kernicterus by glucose-6-phosphate dehydrogenase deficiency: a case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Cossio de Gurrola Gladys

    2008-05-01

    Full Text Available Abstract Introduction Glucose-6-phosphate dehydrogenase deficiency is an X-linked recessive disease that causes acute or chronic hemolytic anemia and potentially leads to severe jaundice in response to oxidative agents. This deficiency is the most common human innate error of metabolism, affecting more than 400 million people worldwide. Case presentation Here, we present the first documented case of kernicterus in Panama, in a glucose-6-phosphate dehydrogenase-deficient newborn clothed in naphthalene-impregnated garments, resulting in reduced psychomotor development, neurosensory hypoacousia, absence of speech and poor reflex of the pupil to light. Conclusion Mutational analysis revealed the glucose-6-phosphate dehydrogenase Mediterranean polymorphic variant, which explained the development of kernicterus after exposition of naphthalene. As the use of naphthalene in stored clothes is a common practice, glucose-6-phosphate dehydrogenase testing in neonatal screening could prevent severe clinical consequences.

  5. 31P-NMR study of human pyrimidine 5'-nucleotidase deficient erythrocytes

    International Nuclear Information System (INIS)

    Higaki, Tsuyoshi; Kagimoto, Tadashi; Nagata, Koichi; Tanase, Sumio; Morino, Yoshimasa; Takatsuki, Kiyoshi

    1982-01-01

    Metabolic disorder of nucleotides in human pyrimidine 5'-nucleotidase (P5N) deficient erythrocytes was studied by 31 P-NMR with high resolution. Identification by combination of high-speed liquid chromatography revealed two-fold increases from the normal in the spectra in the α-, β- and γ-zones of nucleoside triphosphates of P5N deficient erythrocytes, 2,3-diphosphoglycerate shifted to the 0.3 ppm low magnetic field and signals of NAD and UDP-sugars(s) in the diphosphodiester zone. These results were obtained from the 31 P-NMR spectrum about one hour after blood sampling, indicating the high utility of this NMR for the diagnosis of P5N deficiency. (Chiba, N.)

  6. An unusual case of iron deficiency anemia is associated with extremely low level of transferrin receptor.

    Science.gov (United States)

    Hao, Shuangying; Li, Huihui; Sun, Xiaoyan; Li, Juan; Li, Kuanyu

    2015-01-01

    A case study of a female patient, diagnosed with iron deficiency anemia, was unresponsive to oral iron treatment and only partially responsive to parenteral iron therapy, a clinical profile resembling the iron-refractory iron deficiency anemia (IRIDA) disorder. However, the patient failed to exhibit microcytic phenotype, one of the IRIDA hallmarks. Biochemical assays revealed that serum iron, hepcidin, interluekin 6, and transferrin saturation were within the normal range of references or were comparable to her non-anemic offspring. Iron contents in serum and red blood cells and hemoglobin levels were measured, which confirmed the partial improvement of anemia after parenteral iron therapy. Strikingly, serum transferrin receptor in patient was almost undetectable, reflecting the very low activity of bone-marrow erythropoiesis. Our data demonstrate that this is not a case of systemic iron deficiency, but rather cellular iron deficit due to the low level of transferrin receptor, particularly in erythroid tissue.

  7. ODH, oxygen deficiency hazard cryogenic analysis

    International Nuclear Information System (INIS)

    Augustynowicz, S.D.

    1994-01-01

    An oxygen deficiency exists when the concentration of oxygen, by volume, drops to a level at which atmosphere supplying respiratory protection must be provided. Since liquid cryogens can expand by factors of 700 (LN 2 ) to 850 (LH e ), the uncontrolled release into an enclosed space can easily cause an oxygen-deficient condition. An oxygen deficiency hazard (ODH) fatality rate per hour (OE) is defined as: OE = Σ N i P i F i , where N i = number of components, P i = probability of failure or operator error, and F i = fatality factor. ODHs range from open-quotes unclassifiedclose quotes (OE -9 1/h) to class 4, which is the most hazardous (OE>10 -1 1/h). For Superconducting Super Collider Laboratory (SSCL) buildings where cryogenic systems exist, failure rate, fatality factor, reduced oxygen ratio, and fresh air circulation are examined

  8. MRI findings of complete growth hormone deficiency

    International Nuclear Information System (INIS)

    Ichiba, Yozo

    1995-01-01

    Magnetic resonance (MR) imaging was performed on the pituitary gland of 20 children (age range, 2-11 years) with short stature due to growth hormone deficiency. Sixteen patients with multiple pituitary hormone deficiency showed disappearance of the pituitary stalk, disappearance of high signal area of the posterior pituitary, presence of ectopic pituitary, and decreased volume of the anterior pituitary. Many of them had a history of perinatal abnormalities such as asphyxia at delivery, breech delivery, and bradytocia. On the contrary, patients with isolated growth hormone deficiency presented no abnormal findings on MR images, and had no history of perinatal abnormalities. The findings of pituitary stalk separation syndrome suggested the presence of multiple hypopituitarism. (S.Y.)

  9. Growth hormone deficiency and hyperthermia during exercise

    DEFF Research Database (Denmark)

    Juul, A; Hjortskov, N; Jepsen, Leif

    1995-01-01

    -deficiency may be at risk for developing hyperthermia. To pursue this, we performed a controlled study on sweating and body temperature regulation during exercise in the heat in 16 GH-treated GH-deficient patients with normalized insulin-like growth factor-I and insulin-like growth factor/binding protein-3 serum.......001]. Consequently, the core temperatures of the patients increased significantly after exercise compared with those of the CTs [38.3 C (0.10 C) (MPD) and 38.1 C (0.06 C) (isolated GH deficiency) vs. 37.5 C (0.2 C) (CTs) (P temperature increased significantly during exercise in the patients...... but remained unaltered in the CTs. Sweat secretion rates, as determined by the pilocarpine method, were significantly lower in the MPD patients [77 (SE +/- 10) mg/30 min] than in the CTs [115 (SE +/- 7) mg/30 min] (P

  10. Novel targets for ATM-deficient malignancies

    Science.gov (United States)

    Winkler, Johannes; Hofmann, Kay; Chen, Shuhua

    2014-01-01

    Conventional chemo- and radiotherapies for the treatment of cancer target rapidly dividing cells in both tumor and non-tumor tissues and can exhibit severe cytotoxicity in normal tissue and impair the patient's immune system. Novel targeted strategies aim for higher efficacy and tumor specificity. The role of ATM protein in the DNA damage response is well known and ATM deficiency frequently plays a role in tumorigenesis and development of malignancy. In addition to contributing to disease development, ATM deficiency also renders malignant cells heavily dependent on other pathways that cooperate with the ATM-mediated DNA damage response to ensure tumor cell survival. Disturbing those cooperative pathways by inhibiting critical protein components allows specific targeting of tumors while sparing healthy cells with normal ATM status. We review druggable candidate targets for the treatment of ATM-deficient malignancies and the mechanisms underlying such targeted therapies. PMID:27308314

  11. MRI findings of complete growth hormone deficiency

    Energy Technology Data Exchange (ETDEWEB)

    Ichiba, Yozo [National Hospital of Okayama (Japan)

    1995-10-01

    Magnetic resonance (MR) imaging was performed on the pituitary gland of 20 children (age range, 2-11 years) with short stature due to growth hormone deficiency. Sixteen patients with multiple pituitary hormone deficiency showed disappearance of the pituitary stalk, disappearance of high signal area of the posterior pituitary, presence of ectopic pituitary, and decreased volume of the anterior pituitary. Many of them had a history of perinatal abnormalities such as asphyxia at delivery, breech delivery, and bradytocia. On the contrary, patients with isolated growth hormone deficiency presented no abnormal findings on MR images, and had no history of perinatal abnormalities. The findings of pituitary stalk separation syndrome suggested the presence of multiple hypopituitarism. (S.Y.).

  12. Vitamin D Deficiency in Patients with Tuberculosis

    International Nuclear Information System (INIS)

    Iftikhar, R.; Kamran, S. M.; Haider, E.; Qadir, A.; Usman, H. B.

    2013-01-01

    Objective: To determine the frequency and association of Vitamin D deficiency in patients with tuberculosis. Study Design: Case control study. Place and Duration of Study: Medical Department, Combined Military Hospital, Kharian, from July 2010 to June 2012. Methodology: One hundred and five outdoor patients of tuberculosis were selected with 255 gender matched controls. Tuberculosis was diagnosed by presence of acid fast bacilli in sputum smears, positive culture for Mycobacterium tuberculosis or demonstration of chronic caseating granulomatous inflammation in tissue specimens. Controls were drawn randomly from general population. Serum 25 hydroxyvitamin D [25 (OH) D3] levels < 25 ng/ml was considered Vitamin D deficiency. The results were analyzed on SPSS version 17. Results: Mean Vitamin D levels were 23.23 A+- 6.81 ng/ml in cases, 29.27 A+- 8.89 ng/ml in controls (p < 0.0001). Vitamin D deficiency was found in 57% of cases and 33% controls (p < 0.0001). Mean Vitamin D levels were significantly lower in females with tuberculosis (20.84 ng/ml) as compared to males (25.03 ng/ml, p = 0.002). Mean BMI in patients of tuberculosis with Vitamin D deficiency were 19.51 A+- 1.77 kg/m2 and in patients with normal Vitamin D were 21.65 A+- 1.79 kg/m2 (p < 0.0001). Mean Vitamin D levels in patients with multi-drug resistant tuberculosis was lower to a mean of 15.41 A+- 4.67 ng/ml (p < 0.0001). Conclusion: There is significant deficiency of Vitamin D in patients with tuberculosis as compared to controls. This deficiency is more pronounced in females, individuals with low BMI, extra pulmonary and MDR tuberculosis. (author)

  13. Vitamin D deficiency in early pregnancy.

    Directory of Open Access Journals (Sweden)

    Shannon K Flood-Nichols

    Full Text Available Vitamin D deficiency is a common problem in reproductive-aged women in the United States. The effect of vitamin D deficiency in pregnancy is unknown, but has been associated with adverse pregnancy outcomes. The objective of this study was to analyze the relationship between vitamin D deficiency in the first trimester and subsequent clinical outcomes.This is a retrospective cohort study. Plasma was collected in the first trimester from 310 nulliparous women with singleton gestations without significant medical problems. Competitive enzymatic vitamin D assays were performed on banked plasma specimens and pregnancy outcomes were collected after delivery. Logistic regression was performed on patients stratified by plasma vitamin D concentration and the following combined clinical outcomes: preeclampsia, preterm delivery, intrauterine growth restriction, gestational diabetes, and spontaneous abortion.Vitamin D concentrations were obtained from 235 patients (mean age 24.3 years, range 18-40 years. Seventy percent of our study population was vitamin D insufficient with a serum concentration less than 30 ng/mL (mean serum concentration 27.6 ng/mL, range 13-71.6 ng/mL. Logistic regression was performed adjusting for age, race, body mass index, tobacco use, and time of year. Adverse pregnancy outcomes included preeclampsia, growth restriction, preterm delivery, gestational diabetes, and spontaneous abortion. There was no association between vitamin D deficiency and composite adverse pregnancy outcomes with an adjusted odds ratio of 1.01 (p value 0.738, 95% confidence intervals 0.961-1.057.Vitamin D deficiency did not associate with adverse pregnancy outcomes in this study population. However, the high percentage of affected individuals highlights the prevalence of vitamin D deficiency in young, reproductive-aged women.

  14. Survival and psychomotor development with early betaine treatment in patients with severe methylenetetrahydrofolate reductase deficiency.

    Science.gov (United States)

    Diekman, Eugene F; de Koning, Tom J; Verhoeven-Duif, Nanda M; Rovers, Maroeska M; van Hasselt, Peter M

    2014-02-01

    The impact of betaine treatment on outcome in patients with severe methylenetetrahydrofolate reductase (MTHFR) deficiency is presently unclear. To investigate the effect of betaine treatment on development and survival in patients with severe MTHFR deficiency. MEDLINE, EMBASE, and Cochrane databases between January 1960 and December 2012. Studies that described patients with severe MTHFR deficiency who received betaine treatment. We identified 15 case reports and case series, totaling 36 patients. Data included the following: (1) families with 2 or more patients with severe MTHFR deficiency, of whom at least 1 received betaine, or (2) single patients with severe MTHFR deficiency treated with betaine. To define severe MTHFR deficiency, methionine, homocysteine, MTHFR enzyme activity in fibroblasts, or mutations (in the MTHFR gene) had to be described as well as the effect of treatment (survival and/or psychomotor development). We compared the outcome in treated vs untreated patients and early- vs late-treated patients. Sensitivity analysis was performed to address definition of early treatment. To further assess the impact of treatment on mortality, we performed a subanalysis in families with at least 1 untreated deceased patient. Survival and psychomotor development. Eleven of 36 patients (31%) died. All deaths occurred in patients who did not receive treatment or in patients in whom treatment was delayed. In contrast, all 5 early-treated patients survived. Subgroup analysis of patients with deceased siblings-their genotypically identical controls-revealed that betaine treatment prevented mortality (P = .002). In addition, psychomotor development in surviving patients treated with betaine was normal in all 5 early-treated patients but in none of the 19 surviving patients with delayed treatment (P psychomotor development in patients with severe MTHFR deficiency, highlighting the importance of timely recognition through newborn screening.

  15. Acid sphingomyelinase (aSMase) deficiency leads to abnormal microglia behavior and disturbed retinal function

    Energy Technology Data Exchange (ETDEWEB)

    Dannhausen, Katharina; Karlstetter, Marcus; Caramoy, Albert [Laboratory for Experimental Immunology of the Eye, Department of Ophthalmology, University of Cologne, Cologne (Germany); Volz, Cornelia; Jägle, Herbert [Department of Ophthalmology, University Hospital Regensburg, Regensburg (Germany); Liebisch, Gerhard [Institute for Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, Regensburg (Germany); Utermöhlen, Olaf [Institute for Medical Microbiology, Immunology and Hygiene and Center for Molecular Medicine Cologne, University of Cologne, Cologne (Germany); Langmann, Thomas, E-mail: thomas.langmann@uk-koeln.de [Laboratory for Experimental Immunology of the Eye, Department of Ophthalmology, University of Cologne, Cologne (Germany)

    2015-08-21

    Mutations in the acid sphingomyelinase (aSMase) coding gene sphingomyelin phosphodiesterase 1 (SMPD1) cause Niemann-Pick disease (NPD) type A and B. Sphingomyelin storage in cells of the mononuclear phagocyte system cause hepatosplenomegaly and severe neurodegeneration in the brain of NPD patients. However, the effects of aSMase deficiency on retinal structure and microglial behavior have not been addressed in detail yet. Here, we demonstrate that retinas of aSMase{sup −/−} mice did not display overt neuronal degeneration but showed significantly reduced scotopic and photopic responses in electroretinography. In vivo fundus imaging of aSMase{sup −/−} mice showed many hyperreflective spots and staining for the retinal microglia marker Iba1 revealed massive proliferation of retinal microglia that had significantly enlarged somata. Nile red staining detected prominent phospholipid inclusions in microglia and lipid analysis showed significantly increased sphingomyelin levels in retinas of aSMase{sup −/−} mice. In conclusion, the aSMase-deficient mouse is the first example in which microglial lipid inclusions are directly related to a loss of retinal function. - Highlights: • aSMase-deficient mice show impaired retinal function and reactive microgliosis. • aSMase-deficient microglia express pro-inflammatory transcripts. • aSMase-deficient microglia proliferate and have increased cell body size. • In vivo imaging shows hyperreflective spots in the fundus of aSMase-deficient mice. • aSMase-deficient microglia accumulate sphingolipid-rich intracellular deposits.

  16. Selenium Deficiency Influences the mRNA Expression of Selenoproteins and Cytokines in Chicken Erythrocytes.

    Science.gov (United States)

    Luan, Yilin; Zhao, Jinxin; Yao, Haidong; Zhao, Xia; Fan, Ruifeng; Zhao, Wenchao; Zhang, Ziwei; Xu, Shiwen

    2016-06-01

    Selenium (Se) deficiency induces hemolysis in chickens, but the molecular mechanism for this effect remains unclear. Se primarily elicits its function through the activity of selenoproteins, which contain the unique amino acid selenocysteine (Sec). In this study, we aimed to investigate the effect of Se deficiency on the expression of 24 selenoproteins and 10 cytokines. One hundred eighty chickens were randomly divided into 2 groups (90 chickens per group). During the entire experimental period, chickens were allowed ad libitum consumption of feed and water. The chickens were fed either a Se-deficient diet (0.008 mg Se/kg; produced in the Se-deficient area of Heilongjiang, China) or a Se-supplemented diet (as sodium selenite) at 0.2 mg/kg for 35 days. At the 35th day, the messenger RNA (mRNA) levels of 24 selenoproteins and 10 cytokines were examined in erythrocytes of 5 chickens per group, and the correlation was analyzed. The results showed that the expression of 24 selenoproteins and 7 cytokines (IL-2, IL-4, IL-8, IL-10, IL-12β, TGF-β4, and IFN-γ) decreased (P chicken erythrocytes (P chickens was damaged by the Se deficiency. Correlation analysis suggested that although the expression of 24 selenoproteins and 7 cytokines decreased and that of 3 cytokines increased, there was a close correlation between their expression levels and a Se diet. These results suggested that Se deficiency influenced the expressions of 24 selenoproteins and 10 cytokines in chicken erythrocytes, revealing a relationship between Se and the chicken immune system. This study offers information regarding the mechanism of Se deficiency-induced hemolysis.

  17. Iron deficiency anaemia -a risk factor for febrile seizures in children

    International Nuclear Information System (INIS)

    Sherjil, A.; Saeed, Z.U.; Shehzad, S.; Amjad, R.

    2010-01-01

    Background: Iron deficiency anaemia and febrile seizures are two common diseases in children worldwide as well as in our country. Iron insufficiency is known to cause neurological symptoms like behavioural changes, poor attention span and learning deficits in children. Therefore, it may also be associated with other neurological disturbances like febrile seizures in children. Objective of our case-control study was to find association between iron deficiency anaemia and febrile seizures in children. Methods: This multicentre study was conducted in Department of Paediatrics HIT Hospital Taxila Cantt, Department of Paediatrics CMH Mangla and Department of Paediatrics POF Hospital Wah Cantt, from June 2008 to June 2010. Three hundred and ten children aged between 6 months to 6 years were included in the study. One hundred and fifty-seven children who presented with febrile seizures were our cases, while, 153 children who presented with febrile illnesses without seizures were recruited as controls. All patients were assessed for iron deficiency anaemia by measuring haemoglobin level, serum ferritin level, Mean Corpuscular Haemoglobin Concentration (MCHC) and Mean Corpuscular Volume (MCV). Patients with iron deficiency anaemia amongst controls and cases were documented. Percentages and Odds ratio were derived from the collected data. Results: 31.85% of cases (50 out of 157) had iron deficiency anaemia whereas, 19.6% of controls (30 out of 153) were found to have iron deficiency anaemia as revealed by low levels of haemoglobin level, serum ferritin level, Mean Corpuscular Haemoglobin Concentration and Mean Corpuscular Volume. Odds ratio was 1.93. Conclusion: Patients with febrile seizures are 1.93 times more likely to have iron deficiency anaemia compared to febrile patients without seizures. (author)

  18. Strategies to rescue the consequences of inducible arginase-1 deficiency in mice.

    Directory of Open Access Journals (Sweden)

    Laurel L Ballantyne

    Full Text Available Arginase-1 catalyzes the conversion of arginine to ornithine and urea, which is the final step of the urea cycle used to remove excess ammonia from the body. Arginase-1 deficiency leads to hyperargininemia in mice and man with severe lethal consequences in the former and progressive neurological impairment to varying degrees in the latter. In a tamoxifen-induced arginase-1 deficient mouse model, mice succumb to the enzyme deficiency within 2 weeks after inducing the knockout and retain <2 % enzyme in the liver. Standard clinical care regimens for arginase-1 deficiency (low-protein diet, the nitrogen-scavenging drug sodium phenylbutyrate, ornithine supplementation either failed to extend lifespan (ornithine or only minimally prolonged lifespan (maximum 8 days with low-protein diet and drug. A conditional, tamoxifen-inducible arginase-1 transgenic mouse strain expressing the enzyme from the Rosa26 locus modestly extended lifespan of neonatal mice, but not that of 4-week old mice, when crossed to the inducible arginase-1 knockout mouse strain. Delivery of an arginase-1/enhanced green fluorescent fusion construct by adeno-associated viral delivery (rh10 serotype with a strong cytomegalovirus-chicken β-actin hybrid promoter rescued about 30% of male mice with lifespan prolongation to at least 6 months, extensive hepatic expression and restoration of significant enzyme activity in liver. In contrast, a vector of the AAV8 serotype driven by the thyroxine-binding globulin promoter led to weaker liver expression and did not rescue arginase-1 deficient mice to any great extent. Since the induced arginase-1 deficient mouse model displays a much more severe phenotype when compared to human arginase-1 deficiency, these studies reveal that it may be feasible with gene therapy strategies to correct the various manifestations of the disorder and they provide optimism for future clinical studies.

  19. The endoperoxide ascaridol shows strong differential cytotoxicity in nucleotide excision repair-deficient cells

    International Nuclear Information System (INIS)

    Abbasi, Rashda; Efferth, Thomas; Kuhmann, Christine; Opatz, Till; Hao, Xiaojiang; Popanda, Odilia; Schmezer, Peter

    2012-01-01

    Targeting synthetic lethality in DNA repair pathways has become a promising anti-cancer strategy. However little is known about such interactions with regard to the nucleotide excision repair (NER) pathway. Therefore, cell lines with a defect in the NER genes ERCC6 or XPC and their normal counterparts were screened with 53 chemically defined phytochemicals isolated from plants used in traditional Chinese medicine for differential cytotoxic effects. The screening revealed 12 drugs that killed NER-deficient cells more efficiently than proficient cells. Five drugs were further analyzed for IC 50 values, effects on cell cycle distribution, and induction of DNA damage. Ascaridol was the most effective compound with a difference of > 1000-fold in resistance between normal and NER-deficient cells (IC 50 values for cells with deficiency in ERCC6: 0.15 μM, XPC: 0.18 μM, and normal cells: > 180 μM). NER-deficiency combined with ascaridol treatment led to G2/M-phase arrest, an increased percentage of subG1 cells, and a substantially higher DNA damage induction. These results were confirmed in a second set of NER-deficient and -proficient cell lines with isogenic background. Finally, ascaridol was characterized for its ability to generate oxidative DNA damage. The drug led to a dose-dependent increase in intracellular levels of reactive oxygen species at cytotoxic concentrations, but only NER-deficient cells showed a strongly induced amount of 8-oxodG sites. In summary, ascaridol is a cytotoxic and DNA-damaging compound which generates intracellular reactive oxidative intermediates and which selectively affects NER-deficient cells. This could provide a new therapeutic option to treat cancer cells with mutations in NER genes. -- Highlights: ► Thousand-fold higher Ascaridol activity in NER-deficient versus proficient cells. ► Impaired repair of Ascaridol-induced oxidative DNA damage in NER-deficient cells. ► Selective activity of Ascaridol opens new therapy options in

  20. The endoperoxide ascaridol shows strong differential cytotoxicity in nucleotide excision repair-deficient cells

    Energy Technology Data Exchange (ETDEWEB)

    Abbasi, Rashda [Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Efferth, Thomas [Institute of Pharmacy und Biochemistry, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz (Germany); Kuhmann, Christine [Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Opatz, Till [Institute of Organic Chemistry, Johannes Gutenberg University, Duesbergweg 10-14, 55128 Mainz (Germany); Hao, Xiaojiang [Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650204 (China); Popanda, Odilia, E-mail: o.popanda@dkfz.de [Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Schmezer, Peter [Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany)

    2012-03-15

    Targeting synthetic lethality in DNA repair pathways has become a promising anti-cancer strategy. However little is known about such interactions with regard to the nucleotide excision repair (NER) pathway. Therefore, cell lines with a defect in the NER genes ERCC6 or XPC and their normal counterparts were screened with 53 chemically defined phytochemicals isolated from plants used in traditional Chinese medicine for differential cytotoxic effects. The screening revealed 12 drugs that killed NER-deficient cells more efficiently than proficient cells. Five drugs were further analyzed for IC{sub 50} values, effects on cell cycle distribution, and induction of DNA damage. Ascaridol was the most effective compound with a difference of > 1000-fold in resistance between normal and NER-deficient cells (IC{sub 50} values for cells with deficiency in ERCC6: 0.15 μM, XPC: 0.18 μM, and normal cells: > 180 μM). NER-deficiency combined with ascaridol treatment led to G2/M-phase arrest, an increased percentage of subG1 cells, and a substantially higher DNA damage induction. These results were confirmed in a second set of NER-deficient and -proficient cell lines with isogenic background. Finally, ascaridol was characterized for its ability to generate oxidative DNA damage. The drug led to a dose-dependent increase in intracellular levels of reactive oxygen species at cytotoxic concentrations, but only NER-deficient cells showed a strongly induced amount of 8-oxodG sites. In summary, ascaridol is a cytotoxic and DNA-damaging compound which generates intracellular reactive oxidative intermediates and which selectively affects NER-deficient cells. This could provide a new therapeutic option to treat cancer cells with mutations in NER genes. -- Highlights: ► Thousand-fold higher Ascaridol activity in NER-deficient versus proficient cells. ► Impaired repair of Ascaridol-induced oxidative DNA damage in NER-deficient cells. ► Selective activity of Ascaridol opens new therapy