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

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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.

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.

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

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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.

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

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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....

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

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

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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.

Iron-induced oligomerization of human FXN^81-210 and bacterial CyaY frataxin and the effect of iron chelators

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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...

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.

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

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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.

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

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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.

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

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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.

Metal Homeostasis Regulators Suppress FRDA Phenotypes in a Drosophila Model of the Disease.

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Sirena Soriano

Full Text Available Friedreich's ataxia (FRDA, the most commonly inherited ataxia in populations of European origin, is a neurodegenerative disorder caused by a decrease in frataxin levels. One of the hallmarks of the disease is the accumulation of iron in several tissues including the brain, and frataxin has been proposed to play a key role in iron homeostasis. We found that the levels of zinc, copper, manganese and aluminum were also increased in a Drosophila model of FRDA, and that copper and zinc chelation improve their impaired motor performance. By means of a candidate genetic screen, we identified that genes implicated in iron, zinc and copper transport and metal detoxification can restore frataxin deficiency-induced phenotypes. Taken together, these results demonstrate that the metal dysregulation in FRDA includes other metals besides iron, therefore providing a new set of potential therapeutic targets.

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.

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.

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

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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

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.

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

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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

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

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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

2004-12-01

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.

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

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

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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.

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

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.

Carnitine Deficiency and Pregnancy

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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.

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

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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.

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.

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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.

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

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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.

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.

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.

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

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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

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.

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

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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.

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.

Antepartum Ornithine Transcarbamylase Deficiency

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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.

Atypical B12 Deficiency with Nonresolving Paraesthesia

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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.

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.

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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.

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

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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.

Understanding the genetic and molecular pathogenesis of Friedreich’s ataxia through animal and cellular models

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Martelli, Alain; Napierala, Marek; Puccio, Hélène

2012-01-01

In 1996, a link was identified between Friedreich’s ataxia (FRDA), the most common inherited ataxia in men, and alterations in the gene encoding frataxin (FXN). Initial studies revealed that the disease is caused by a unique, most frequently biallelic, expansion of the GAA sequence in intron 1 of FXN. Since the identification of this link, there has been tremendous progress in understanding frataxin function and the mechanism of FRDA pathology, as well as in developing diagnostics and therapeutic approaches for the disease. These advances were the subject of the 4th International Friedreich’s Ataxia Conference held on 5th–7th May in the Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France. More than 200 scientists gathered from all over the world to present the results of research spanning all areas of investigation into FRDA (including clinical aspects, FRDA pathogenesis, genetics and epigenetics of the disease, development of new models of FRDA, and drug discovery). This review provides an update on the understanding of frataxin function, developments of animal and cellular models of the disease, and recent advances in trying to uncover potential molecules for therapy. PMID:22382366

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

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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.

Iron deficiency alters megakaryopoiesis and platelet phenotype independent of thrombopoietin.

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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.

Myoadenylate deaminase deficiency, hypertrophic cardiomyopathy and gigantism syndrome.

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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.

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

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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

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

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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

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

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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.

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

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

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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.

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.

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 ...

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...

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.

Molecular Alterations in a Mouse Cardiac Model of Friedreich Ataxia

DEFF Research Database (Denmark)

Anzovino, Amy; Chiang, Shannon; Brown, Bronwyn E

2017-01-01

mechanisms. Using a mouse conditional frataxin knockout (KO) model in the heart and skeletal muscle, we examined the Nrf2 pathway in these tissues. Frataxin KO results in fatal cardiomyopathy, whereas skeletal muscle was asymptomatic. In the KO heart, protein oxidation and a decreased glutathione...

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

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.

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

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.

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

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)

A rare form of Gaucher disease resulting from saposin C deficiency.

Science.gov (United States)

Kang, Lulu; Zhan, Xia; Ye, Jun; Han, Lianshu; Qiu, Wenjuan; Gu, Xuefan; Zhang, Huiwen

2018-02-01

Gaucher disease is mainly caused by the deficiency of lysosomal acid β-glucosidase. Gaucher disease caused by the deficiency of saposin C is rare. Here we report a patient mainly presenting with hepatosplenomegaly, thrombocytopenia and anemia. EEG examination revealed increased theta waves. Gaucher cells identified in his bone marrow and the highly elevated plasma chitotriosidase activity and glucosylsphingosine supported a diagnosis of Gaucher disease. However, the leukocyte β-glucosidase activity was in a normal range. Sanger sequencing revealed a novel maternal exonic mutation c.1133C>G (p.Pro378Arg) in exon 10 of the PSAP gene, which codes the Sap C domain of PSAP protein. To search for other underlying mutations in this patient, whole genome sequencing was applied and revealed a deletion involving exon 2 to 7 of PSAP gene. The deletion appears as a de novo event on paternal chromosome. We concluded that biallelic mutations of PSAP gene were the cause of this patient's Gaucher disease. Our finding expands the mutation spectrum of Gaucher disease with saposin C deficiency. Copyright © 2017 Elsevier Inc. All rights reserved.

Transient Ischemic Attack Caused by Iron Deficiency Anemia

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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

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 ...

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.

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.

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.

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.

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.

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 ...

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.

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.

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.

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.

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 ...

Iron-Deficiency Anemia

Medline Plus

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 ...

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.

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.

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)

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...

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.

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

Novel Mitochondrial Homoplasmic T4216C Mutation in Iranian Patients with Friedreich Ataxia

Directory of Open Access Journals (Sweden)

M Heidari

2010-06-01

Full Text Available Introduction: The mitochondrial defects in Friedreich ataxia (FRDA have been reported in many researches. Friedreich ataxia is an autosomal recessive neurodegenerative disorder caused by decreased expression of the Frataxin protein. Frataxin deficiency leads to excessive free radical production and dysfunction of respiratory chain complexes. Mitochondrial DNA (mtDNA could be considered as a candidate modifier factor for FRDA disease. It prompted us to focus on the mtDNA and monitor the nucleotide changes of genome which are probably the cause of respiratory chain defects and reduced ATP generation. Methods: We searched the mitochondrial NADH dehydroganase I (ND1 gene by PCR-TTGE and DNA fragments showing abnormal banding patterns were sequenced for the identification of exact mutations. Results: In 20 patients, we detected 3 mtDNA mutations which is novel in Friedreich ataxia. T4216C mutation results in conversion of Tyrosine to Histidine in 313 amino acid locations in ND1 and bioinformatics studies show that ND1 protein loses sixth intramembrane α chain. Conclusion: Our results showed that ND1 gene mutations in FRDA samples are higher than normal controls (P<0.001. It is possible that mutations in mtDNA could constitute a predisposing factor in combination with environmental risk factors that could affect the age of onset and rate of disease progression.

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

Iron-Deficiency Anemia

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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- ...

Lipoprotein lipase deficiency with visceral xanthomas

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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.)

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.

Meta-analysis of melanin-concentrating hormone signaling-deficient mice on behavioral and metabolic phenotypes.

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Kenkichi Takase

Full Text Available The demand for meta-analyses in basic biomedical research has been increasing because the phenotyping of genetically modified mice does not always produce consistent results. Melanin-concentrating hormone (MCH has been reported to be involved in a variety of behaviors that include feeding, body-weight regulation, anxiety, sleep, and reward behavior. However, the reported behavioral and metabolic characteristics of MCH signaling-deficient mice, such as MCH-deficient mice and MCH receptor 1 (MCHR1-deficient mice, are not consistent with each other. In the present study, we performed a meta-analysis of the published data related to MCH-deficient and MCHR1-deficient mice to obtain robust conclusions about the role of MCH signaling. Overall, the meta-analysis revealed that the deletion of MCH signaling enhanced wakefulness, locomotor activity, aggression, and male sexual behavior and that MCH signaling deficiency suppressed non-REM sleep, anxiety, responses to novelty, startle responses, and conditioned place preferences. In contrast to the acute orexigenic effect of MCH, MCH signaling deficiency significantly increased food intake. Overall, the meta-analysis also revealed that the deletion of MCH signaling suppressed the body weight, fat mass, and plasma leptin, while MCH signaling deficiency increased the body temperature, oxygen consumption, heart rate, and mean arterial pressure. The lean phenotype of the MCH signaling-deficient mice was also confirmed in separate meta-analyses that were specific to sex and background strain (i.e., C57BL/6 and 129Sv. MCH signaling deficiency caused a weak anxiolytic effect as assessed with the elevated plus maze and the open field test but also caused a weak anxiogenic effect as assessed with the emergence test. MCH signaling-deficient mice also exhibited increased plasma corticosterone under non-stressed conditions, which suggests enhanced activity of the hypothalamic-pituitary-adrenal axis. To the best of our

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

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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.

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

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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.

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

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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.

Present status of understanding on the G6PD deficiency and natural selection

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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.

Risk Factors of Development of Iron-Deficiency Conditions in Moscow Adolescents

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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. 

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.)

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

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 ...

Folic acid deficiency optic neuropathy: A case report

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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.

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

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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.

Cobalamin deficiency, hyperhomocysteinemia, and dementia

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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

Gender affects skin wound healing in plasminogen deficient mice.

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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

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...

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 ...

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 ...

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...

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 ...

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. ...

Iron-Deficiency Anemia

Medline Plus

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 ...

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

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)

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.

Iron-Deficiency Anemia

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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 ...

Health Deficiencies

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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,...

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.

Iron-Deficiency Anemia

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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 ...

Iron-Deficiency Anemia

Medline Plus

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 ...

Biotinidase deficiency: a reversible metabolic encephalopathy. Neuroimaging and MR spectroscopic findings in a series of four patients

International Nuclear Information System (INIS)

Desai, Shrinivas; Ganesan, Karthik; Hegde, Anaita

2008-01-01

Biotinidase deficiency is a metabolic disorder characterized by inability to recycle biotin with resultant delayed myelination. Clinical findings include seizures, ataxia, alopecia and dermatitis with atypical findings of myoclonic jerks, neuropathy and spastic paraparesis. Neuroradiological findings include cerebral atrophy, encephalopathy and widened extracerebral CSF spaces. Many of the clinical and neuroradiological features are reversible except sensorineural hearing loss and optic atrophy. To understand and describe the neuroimaging and spectroscopic findings of biotinidase deficiency. We evaluated the spectrum of neuroimaging and spectroscopic findings in four patients with biotinidase deficiency with follow-up studies in three patients. The imaging findings were encephalopathy, low cerebral volume, ventriculomegaly and widened extracerebral CSF spaces. Uncommon findings were caudate involvement, parieto-occipital cortical abnormalities and one patient with restricted diffusion. Two patients had subdural effusions, which is uncommon in biotinidase deficiency. 1 H-MR spectroscopy revealed elevated lactate, reversal of the choline/creatine ratio and decreased NAA peaks. Follow-up studies revealed complete reversal of imaging findings in two patients. Biotinidase deficiency is a reversible metabolic encephalopathy. This study highlights the importance of early and prompt cliniconeuroradiological diagnosis of biotinidase deficiency as it has an extremely good clinical outcome if treatment is initiated from early infancy. (orig.)

Biotinidase deficiency: a reversible metabolic encephalopathy. Neuroimaging and MR spectroscopic findings in a series of four patients

Energy Technology Data Exchange (ETDEWEB)

Desai, Shrinivas [Jaslok Hospital and Research Centre, Department of CT and MRI, Mumbai (India); Ganesan, Karthik [Jaslok Hospital and Research Centre, Department of CT and MRI, Mumbai (India); University of California, San Diego, Department of Radiology, San Diego, CA (United States); Hegde, Anaita [Jaslok Hospital and Research Centre, Department of Paediatrics, Mumbai (India)

2008-08-15

Biotinidase deficiency is a metabolic disorder characterized by inability to recycle biotin with resultant delayed myelination. Clinical findings include seizures, ataxia, alopecia and dermatitis with atypical findings of myoclonic jerks, neuropathy and spastic paraparesis. Neuroradiological findings include cerebral atrophy, encephalopathy and widened extracerebral CSF spaces. Many of the clinical and neuroradiological features are reversible except sensorineural hearing loss and optic atrophy. To understand and describe the neuroimaging and spectroscopic findings of biotinidase deficiency. We evaluated the spectrum of neuroimaging and spectroscopic findings in four patients with biotinidase deficiency with follow-up studies in three patients. The imaging findings were encephalopathy, low cerebral volume, ventriculomegaly and widened extracerebral CSF spaces. Uncommon findings were caudate involvement, parieto-occipital cortical abnormalities and one patient with restricted diffusion. Two patients had subdural effusions, which is uncommon in biotinidase deficiency. {sup 1}H-MR spectroscopy revealed elevated lactate, reversal of the choline/creatine ratio and decreased NAA peaks. Follow-up studies revealed complete reversal of imaging findings in two patients. Biotinidase deficiency is a reversible metabolic encephalopathy. This study highlights the importance of early and prompt cliniconeuroradiological diagnosis of biotinidase deficiency as it has an extremely good clinical outcome if treatment is initiated from early infancy. (orig.)

Time course and pattern of compensatory ingestive behavioral adjustments to lysine deficiency in rats.

Science.gov (United States)

Markison, S; Thompson, B L; Smith, J C; Spector, A C

2000-05-01

We and others have demonstrated that rats deficient in an essential amino acid (EAA) will consume sufficient quantities of the lacking nutrient to produce repletion when it is made available in solution. In the current series of experiments, we made rats deficient in lysine (LYS) by limiting the level of this EAA in the diet. We then examined licking behavior during approximately 23-h two-bottle intake tests over 4 consecutive days. In three separate experiments, rats were presented with the following: 1) 0.1 mol/L LYS and water, 2) 0.2 mol/L threonine (THR) and water and 3) 0.1 mol/L LYS and 0.2 mol/L THR. Lysine-deficient (LYS-DEF) rats drink significantly more LYS than did nondepleted controls (CON) when this amino acid was available. Meal pattern analysis revealed that the enhanced intake of LYS occurred as a function of a greater number of ingestive bouts, not changes in bout size. A cumulative analysis of LYS intake between CON and LYS-DEF rats revealed that a potentiation of intake developed within 30 min of sampling the solution when LYS and water were available and within 90 min when LYS and THR were the contrasting choices. In conclusion, increased LYS intake in the deficient rats occurs relatively rapidly and appears to be at least somewhat specific. Moreover, LYS deficiency does not seem to enhance the palatability of the limiting amino acid as judged by behaviors such as lick rate and bout size. Instead, LYS-DEF rats relieve the deficiency by increasing the number of drinking episodes initiated.

A combined nucleic acid and protein analysis in Friedreich ataxia: implications for diagnosis, pathogenesis and clinical trial design.

Directory of Open Access Journals (Sweden)

Francesco Saccà

Full Text Available BACKGROUND: Friedreich's ataxia (FRDA is the most common hereditary ataxia among caucasians. The molecular defect in FRDA is the trinucleotide GAA expansion in the first intron of the FXN gene, which encodes frataxin. No studies have yet reported frataxin protein and mRNA levels in a large cohort of FRDA patients, carriers and controls. METHODOLOGY/PRINCIPAL FINDINGS: We enrolled 24 patients with classic FRDA phenotype (cFA, 6 late onset FRDA (LOFA, all homozygous for GAA expansion, 5 pFA cases who harbored the GAA expansion in compound heterozygosis with FXN point mutations (namely, p.I154F, c.482+3delA, p.R165P, 33 healthy expansion carriers, and 29 healthy controls. DNA was genotyped for GAA expansion, mRNA/FXN was quantified in real-time, and frataxin protein was measured using lateral-flow immunoassay in peripheral blood mononuclear cells (PBMCs. Mean residual levels of frataxin, compared to controls, were 35.8%, 65.6%, 33%, and 68.7% in cFA, LOFA, pFA and healthy carriers, respectively. Comparison of both cFA and pFA with controls resulted in 100% sensitivity and specificity, but there was overlap between LOFA, carriers and controls. Frataxin levels correlated inversely with GAA1 and GAA2 expansions, and directly with age at onset. Messenger RNA expression was reduced to 19.4% in cFA, 50.4% in LOFA, 52.7% in pFA, 53.0% in carriers, as compared to controls (p<0.0001. mRNA levels proved to be diagnostic when comparing cFA with controls resulting in 100% sensitivity and specificity. In cFA and LOFA patients mRNA levels correlated directly with protein levels and age at onset, and inversely with GAA1 and GAA2. CONCLUSION/SIGNIFICANCE: We report the first explorative study on combined frataxin and mRNA levels in PBMCs from a cohort of FRDA patients, carriers and healthy individuals. Lateral-flow immunoassay differentiated cFA and pFA patients from controls, whereas determination of mRNA in q-PCR was sensitive and specific only in cFA.

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.).

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...

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.

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.

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.

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.

Radio-sensitization of WRN helicase deficient cancer cells by targeting homologous recombination pathway

International Nuclear Information System (INIS)

Gupta, Pooja; Saha, Bhaskar; Patro, Birija Sankar; Chattopadhyay, Subrata

2016-01-01

Ionizing radiation (IR) induced DNA double-strand breaks (DSBs) are primarily repaired by non-homologous end joining (NHEJ). However, it is well established that a subset DSBs which are accumulated in IR-induced G2 phase are dependent on homologous recombination (HR). DNA repair deficient tumor cells have been shown to accumulate high levels of DNA damage. Consequently, these cells become hyperdependent on DNA damage response pathways, including the CHK1-kinase-mediated HR-repair. These observations suggest that DNA repair deficient tumors should exhibit increased radio-sensitivity under HR inhibition. Genetic defects leading to functional loss of werner (WRN) protein is associated with genomic instability and increased cancer incidence. WRN function is known to be abrogated in several human cancer cells due to hypermethylation of CpGisland-promoter and transcriptional silencing of WRN gene. In the current investigation, using isogenic pairs of cell lines differing only in the WRN function, we showed that WRN-deficient cell lines were hyper-radiosensitive to CHK1 pharmacologic inhibition. Here, we found that unrepaired DSB was drastically increased in WRN-deficient cells vis-à-vis WRN-proficient cells in response to IR and CHK1 inhibitor (CHK1i). Our results revealed a marginal role of NHEJ pathway accountable for the radio-sensitivity of WRN-deficient cells. Interestingly, silencing CTIP, a HR protein required for RAD51 loading, significantly abrogated the CHK1i-mediated radiosensitivity in WRN-deficient cells. Silencing of WRN or CTIP individually led to no significant difference in the extent of DNA end resection, as required during HR pathway. Imperatively, our results revealed that WRN and CTIP together play a complementary role in executing DNA end resection during HR-mediated repair of IR induced DSBs. Altogether, our data indicated that inhibition of IR-induced HR pathway at RAD51 loading, but not at DSB end resection, make the WRN-deficient cancer cells

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.

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...

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.

Associations between Zinc Deficiency and Metabolic Abnormalities in Patients with Chronic Liver Disease

Directory of Open Access Journals (Sweden)

Takashi Himoto

2018-01-01

Full Text Available Zinc (Zn is an essential trace element which has favorable antioxidant, anti-inflammatory, and apoptotic effects. The liver mainly plays a crucial role in maintaining systemic Zn homeostasis. Therefore, the occurrence of chronic liver diseases, such as chronic hepatitis, liver cirrhosis, or fatty liver, results in the impairment of Zn metabolism, and subsequently Zn deficiency. Zn deficiency causes plenty of metabolic abnormalities, including insulin resistance, hepatic steatosis and hepatic encephalopathy. Inversely, metabolic abnormalities like hypoalbuminemia in patients with liver cirrhosis often result in Zn deficiency. Recent studies have revealed the putative mechanisms by which Zn deficiency evokes a variety of metabolic abnormalities in chronic liver disease. Zn supplementation has shown beneficial effects on such metabolic abnormalities in experimental models and actual patients with chronic liver disease. This review summarizes the pathogenesis of metabolic abnormalities deriving from Zn deficiency and the favorable effects of Zn administration in patients with chronic liver disease. In addition, we also highlight the interactions between Zn and other trace elements, vitamins, amino acids, or hormones in such patients.

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

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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.

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.

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.

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.

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 ...

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

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.

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

Deficiency of Carbonic Anhydrase II Results in a Urinary Concentrating Defect

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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.

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.

Iron deficiency regulated OsOPT7 is essential for iron homeostasis in rice.

Science.gov (United States)

Bashir, Khurram; Ishimaru, Yasuhiro; Itai, Reiko Nakanishi; Senoura, Takeshi; Takahashi, Michiko; An, Gynheung; Oikawa, Takaya; Ueda, Minoru; Sato, Aiko; Uozumi, Nobuyuki; Nakanishi, Hiromi; Nishizawa, Naoko K

2015-05-01

The molecular mechanism of iron (Fe) uptake and transport in plants are well-characterized; however, many components of Fe homeostasis remain unclear. We cloned iron-deficiency-regulated oligopeptide transporter 7 (OsOPT7) from rice. OsOPT7 localized to the plasma membrane and did not transport Fe(III)-DMA or Fe(II)-NA and GSH in Xenopus laevis oocytes. Furthermore OsOPT7 did not complement the growth of yeast fet3fet4 mutant. OsOPT7 was specifically upregulated in response to Fe-deficiency. Promoter GUS analysis revealed that OsOPT7 expresses in root tips, root vascular tissue and shoots as well as during seed development. Microarray analysis of OsOPT7 knockout 1 (opt7-1) revealed the upregulation of Fe-deficiency-responsive genes in plants grown under Fe-sufficient conditions, despite the high Fe and ferritin concentrations in shoot tissue indicating that Fe may not be available for physiological functions. Plants overexpressing OsOPT7 do not exhibit any phenotype and do not accumulate more Fe compared to wild type plants. These results indicate that OsOPT7 may be involved in Fe transport in rice.

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

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).

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 ...

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 ...

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...

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.

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.

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)

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 ...

Factor VII deficiency

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... 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 ...

Immunoproteasome subunit ß5i/LMP7-deficiency in atherosclerosis.

Science.gov (United States)

Hewing, Bernd; Ludwig, Antje; Dan, Cristian; Pötzsch, Max; Hannemann, Carmen; Petry, Andreas; Lauer, Dilyara; Görlach, Agnes; Kaschina, Elena; Müller, Dominik N; Baumann, Gert; Stangl, Verena; Stangl, Karl; Wilck, Nicola

2017-10-17

Management of protein homeostasis by the ubiquitin-proteasome system is critical for atherosclerosis development. Recent studies showed controversial results on the role of immunoproteasome (IP) subunit β5i/LMP7 in maintenance of protein homeostasis under cytokine induced oxidative stress. The present study aimed to investigate the effect of β5i/LMP7-deficiency on the initiation and progression of atherosclerosis as a chronic inflammatory, immune cell driven disease. LDLR -/- LMP7 -/- and LDLR -/- mice were fed a Western-type diet for either 6 or 24 weeks to induce early and advanced stage atherosclerosis, respectively. Lesion burden was similar between genotypes in both stages. Macrophage content and abundance of polyubiquitin conjugates in aortic root plaques were unaltered by β5i/LMP7-deficiency. In vitro experiments using bone marrow-derived macrophages (BMDM) showed that β5i/LMP7-deficiency did not influence macrophage polarization or accumulation of polyubiquitinated proteins and cell survival upon hydrogen peroxide and interferon-γ treatment. Analyses of proteasome core particle composition by Western blot revealed incorporation of standard proteasome subunits in β5i/LMP7-deficient BMDM and spleen. Chymotrypsin-, trypsin- and caspase-like activities assessed by using short fluorogenic peptides in BMDM whole cell lysates were similar in both genotypes. Taken together, deficiency of IP subunit β5i/LMP7 does not disturb protein homeostasis and does not aggravate atherogenesis in LDLR -/- mice.

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

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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.

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.

Thiamine deficiency impairs common eider (Somateria mollissima) reproduction in the field.

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Mörner, Torsten; Hansson, Tomas; Carlsson, Le; Berg, Anna-Lena; Ruiz Muñoz, Yolanda; Gustavsson, Hanna; Mattsson, Roland; Balk, Lennart

2017-10-31

The Baltic Sea population of the common eider (Somateria mollissima) has declined dramatically during the last two decades. Recently, widespread episodic thiamine (vitamin B 1 ) deficiency has been demonstrated in feral birds and suggested to contribute significantly to declining populations. Here we show that the decline of the common eider population in the Baltic Sea is paralleled by high mortality of the pulli a few days after hatch, owing to thiamine deficiency and probably also thereby associated abnormal behaviour resulting in high gull predation. An experiment with artificially incubated common eider eggs collected in the field revealed that thiamine treatment of pulli had a therapeutic effect on the thiamine status of the brain and prevented death. The mortality was 53% in untreated specimens, whereas it was only 7% in thiamine treated specimens. Inability to dive was also linked to brain damage typical for thiamine deficiency. Our results demonstrate how thiamine deficiency causes a range of symptoms in the common eider pulli, as well as massive die-offs a few days after hatch, which probably are the major explanation of the recent dramatic population declines.

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.

The human cyclin B1 protein modulates sensitivity of DNA mismatch repair deficient prostate cancer cell lines to alkylating agents.

Science.gov (United States)

Rasmussen, L J; Rasmussen, M; Lützen, A; Bisgaard, H C; Singh, K K

2000-05-25

DNA damage caused by alkylating agents results in a G2 checkpoint arrest. DNA mismatch repair (MMR) deficient cells are resistant to killing by alkylating agents and are unable to arrest the cell cycle in G2 phase after alkylation damage. We investigated the response of two MMR-deficient prostate cancer cell lines DU145 and LNCaP to the alkylating agent MNNG. Our studies reveal that DU145 cancer cells are more sensitive to killing by MNNG than LNCaP. Investigation of the underlying reasons for lower resistance revealed that the DU145 cells contain low endogenous levels of cyclin B1. We provide direct evidence that the endogenous level of cyclin B1 modulates the sensitivity of MMR-deficient prostate cancer cells to alkylating agents.

Alpha-1-antitrypsin deficiency in Madeira (Portugal): the highest prevalence in the world.

Science.gov (United States)

Spínola, Carla; Bruges-Armas, Jácome; Pereira, Conceição; Brehm, António; Spínola, Hélder

2009-10-01

Alpha-1-antitrypsin (AAT) deficiency is a common genetic disease which affects both lung and liver. Early diagnosis can help asymptomatic patients to adjust their lifestyle choices in order to reduce the risk of Chronic Obstructive Pulmonary Disease (COPD). The determination of this genetic deficiency prevalence in Madeira Island (Portugal) population is important to clarify susceptibility and define the relevance of performing genetic tests for AAT on individuals at risk for COPD. Two hundred samples of unrelated individuals from Madeira Island were genotyped for the two most common AAT deficiency alleles, PI*S and PI*Z, using Polymerase Chain Reaction-Mediated Site-Directed Mutagenesis. Our results show one of the highest frequencies for both mutations when compared to any already studied population in the world. In fact, PI*S mutation has the highest prevalence (18%), and PI*Z mutation (2.5%) was the third highest worldwide. The frequency of AAT deficiency genotypes in Madeira (PI*ZZ, PI*SS, and PI*SZ) is estimated to be the highest in the world: 41 per 1000. This high prevalence of AAT deficiency on Madeira Island reveals an increased genetic susceptibility to COPD and suggests a routine genetic testing for individuals at risk.

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 ... to iron-deficiency anemia include: End-stage kidney failure, where there is blood loss during dialysis. People ...

Iron-Deficiency Anemia

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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 ...

Iron-Deficiency Anemia

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Iron-Deficiency Anemia

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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 ...

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. ...

Iron-Deficiency Anemia

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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 ...

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. ...

Iron-Deficiency Anemia

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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 ...

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 . ...

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 ...

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

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 ...

Noninvasive evaluation of adult onset myopathy from carnitine palmitoyl transferase II deficiency using proton magnetic resonance spectroscopy.

Science.gov (United States)

Videen, J S; Haseler, L J; Karpinski, N C; Terkeltaub, R A

1999-08-01

The adult onset metabolic myopathy of carnitine palmitoyl transferase II (CPT II) deficiency is under-recognized, in part due to variable degrees of enzyme deficiency and symptomatology, as well as limitations in means for noninvasive evaluation. We describe a proton magnetic resonance spectroscopy (MRS) technique, using a standard clinical magnetic resonance imaging scanner, to diagnose and help monitor the response to therapy in adult CPT II deficiency. A 53-year-old woman presented with a long standing history of diffuse aching and fatigue provoked by high fat intake, fasting, or prolonged exertion. Muscle biopsy revealed myopathic features and a deficiency (33% of control) of CPT II activity with elevated palmitoyl carnitine. Proton MRS of the soleus muscle was performed using a 1.5 Tesla scanner before and during dietary therapy. Proton MRS revealed shortening of the transverse relaxation time (T2), consistent with increased acetylation of the carnitine pool. The symptoms resolved completely by treatment with frequent feedings of a high carbohydrate diet low in long chain fatty acids supplemented with medium chain triglycerides and L-carnitine. Recovery of normal muscle MRS and carnitine T2 relaxation was documented by the third month of therapy. Proton MRS is a novel, potentially useful, and readily available adjunct in the diagnosis and therapeutic monitoring of muscle CPT II deficiency.

[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

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 ...

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 ...

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 ...

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.

Iron-Deficiency Anemia

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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 ...

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 ...

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 ...

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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 ...

C1q nephropathy and isolated CD59 deficiency manifesting as necrotizing crescentic glomerulonephritis: A rare association of two diseases

Directory of Open Access Journals (Sweden)

Ruchika Gupta

2015-01-01

Full Text Available C1q nephropathy is a recently described clinico-pathologic entity with a variable clinical presentation and pathology. Crescentic glomerulonephritis (GN has been reported in only two patients in the available literature. CD59 deficiency, along with lack of CD55, is responsible for paroxysmal nocturnal hemoglobinuria (PNH. Few cases of isolated CD59 deficiency have been described with PNH-like features. A middle-aged adult male presented with rapidly progressive renal failure. Serological investigations were negative. A renal biopsy revealed necrotizing crescentic GN with rupture of Bowman′s capsule. Immunofluorescence on the frozen sections showed dominant mesangial deposits of C1q along with IgM. Hematological work-up of the patient revealed isolated CD59 deficiency. Hence, a final diagnosis of C1q nephropathy and CD59 deficiency manifesting as crescentic GN and hemolytic anemia was made. The co-existence of two rare disorders, C1q nephropathy and CD59 deficiency, in a patient with necrotizing crescentic GN is described for the first time to the best of our knowledge. The pathogenetic link of these two entities with the clinical manifestation requires further study.

Progression from isolated growth hormone deficiency to combined pituitary hormone deficiency.

Science.gov (United States)

Cerbone, Manuela; Dattani, Mehul T

2017-12-01

Growth hormone deficiency (GHD) can present at any time of life from the neonatal period to adulthood, as a result of congenital or acquired insults. It can present as an isolated problem (IGHD) or in combination with other pituitary hormone deficiencies (CPHD). Pituitary deficits can evolve at any time from GHD diagnosis. The number, severity and timing of occurrence of additional endocrinopathies are highly variable. The risk of progression from IGHD to CPHD in children varies depending on the etiology (idiopathic vs organic). The highest risk is displayed by children with abnormalities in the Hypothalamo-Pituitary (H-P) region. Heterogeneous data have been reported on the type and timing of onset of additional pituitary hormone deficits, with TSH deficiency being most frequent and Diabetes Insipidus the least frequent additional deficit in the majority, but not all, of the studies. ACTH deficiency may gradually evolve at any time during follow-up in children or adults with childhood onset IGHD, particularly (but not only) in presence of H-P abnormalities and/or TSH deficiency. Hence there is a need in these patients for lifelong monitoring for ACTH deficiency. GH treatment unmasks central hypothyroidism mainly in patients with organic GHD, but all patients starting GH should have their thyroid function monitored closely. Main risk factors for development of CPHD include organic etiology, H-P abnormalities (in particular pituitary stalk abnormalities, empty sella and ectopic posterior pituitary), midline brain (corpus callosum) and optic nerves abnormalities, genetic defects and longer duration of follow-up. The current available evidence supports longstanding recommendations for the need, in all patients diagnosed with IGHD, of a careful and indefinite follow-up for additional pituitary hormone deficiencies. Copyright © 2017 Elsevier Ltd. All rights reserved.

In HepG2 Cells, Coexisting Carnitine Deficiency Masks Important Indicators of Marginal Biotin Deficiency123

Science.gov (United States)

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

2015-01-01

Background: 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. Objective: In this study we hypothesized that coexisting carnitine deficiency can prevent the increase in 3HIAc due to biotin deficiency. Methods: 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. Results: 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

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...

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...

Malonyl CoA decarboxylase deficiency: C to T transition in intron 2 of the MCD gene.

Science.gov (United States)

Surendran, S; Sacksteder, K A; Gould, S J; Coldwell, J G; Rady, P L; Tyring, S K; Matalon, R

2001-09-15

Malonyl CoA decarboxylase (MCD) is an enzyme involved in the metabolism of fatty acids synthesis. Based on reports of MCD deficiency, this enzyme is particular important in muscle and brain metabolism. Mutations in the MCD gene result in a deficiency of MCD activity, that lead to psychomotor retardation, cardiomyopathy and neonatal death. To date however, only a few patients have been reported with defects in MCD. We report here studies of a patient with MCD deficiency, who presented with hypotonia, cardiomyopathy and psychomotor retardation. DNA sequencing of MCD revealed a homozygous intronic mutation, specifically a -5 C to T transition near the acceptor site for exon 3. RT-PCR amplification of exons 2 and 3 revealed that although mRNA from a normal control sample yielded one major DNA band, the mutant mRNA sample resulted in two distinct DNA fragments. Sequencing of the patient's two RT-PCR products revealed that the larger molecular weight fragments contained exons 2 and 3 as well as the intervening intronic sequence. The smaller size band from the patient contained the properly spliced exons, similar to the normal control. Western blotting analysis of the expressed protein showed only a faint band in the patient sample in contrast to a robust band in the control. In addition, the enzyme activity of the mutant protein was lower than that of the control protein. The data indicate that homozygous mutation in intron 2 disrupt normal splicing of the gene, leading to lower expression of the MCD protein and MCD deficiency. Copyright 2001 Wiley-Liss, Inc.

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 ...

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

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.

Possible contribution of taurine to distorted glucagon secretion in intra-islet insulin deficiency: a metabolome analysis using a novel α-cell model of insulin-deficient diabetes.

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Megumi Bessho

Full Text Available Glycemic instability is a serious problem in patients with insulin-deficient diabetes, and it may be due in part to abnormal endogenous glucagon secretion. However, the intracellular metabolic mechanism(s involved in the aberrant glucagon response under the condition of insulin deficiency has not yet been elucidated. To investigate the metabolic traits that underlie the distortion of glucagon secretion under insulin deficient conditions, we generated an αTC1-6 cell line with stable knockdown of the insulin receptor (IRKD, i.e., an in vitro α-cell model for insulin-deficient diabetes, which exhibits an abnormal glucagon response to glucose. A comprehensive metabolomic analysis of the IRKD αTC1-6 cells (IRKD cells revealed some candidate metabolites whose levels differed markedly compared to those in control αTC1-6 cells, but also which could affect the glucagon release in IRKD cells. Of these candidates, taurine was remarkably increased in the IRKD cells and was identified as a stimulator of glucagon in αTC1-6 cells. Taurine also paradoxically exaggerated the glucagon secretion at a high glucose concentration in IRKD cells and islets with IRKD. These results indicate that the metabolic alterations induced by IRKD in α-cells, especially the increase of taurine, may lead to the distorted glucagon response in IRKD cells, suggesting the importance of taurine in the paradoxical glucagon response and the resultant glucose instability in insulin-deficient diabetes.

Data on xylem sap proteins from Mn- and Fe-deficient tomato plants obtained using shotgun proteomics.

Science.gov (United States)

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

2018-04-01

This article contains consolidated proteomic data obtained from xylem sap collected from tomato plants grown in Fe- and Mn-sufficient control, as well as Fe-deficient and Mn-deficient conditions. Data presented here cover proteins identified and quantified by shotgun proteomics and Progenesis LC-MS analyses: proteins identified with at least two peptides and showing changes statistically significant (ANOVA; p ≤ 0.05) and above a biologically relevant selected threshold (fold ≥ 2) between treatments are listed. The comparison between Fe-deficient, Mn-deficient and control xylem sap samples using a multivariate statistical data analysis (Principal Component Analysis, PCA) is also included. Data included in this article are discussed in depth in the research article entitled "Effects of Fe and Mn deficiencies on the protein profiles of tomato ( Solanum lycopersicum) xylem sap as revealed by shotgun analyses" [1]. This dataset is made available to support the cited study as well to extend analyses at a later stage.

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 ...

Iron deficiency anemia

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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 ...

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...

Metabolome and proteome profiling of complex I deficiency induced by rotenone.

Science.gov (United States)

Gielisch, Ina; Meierhofer, David

2015-01-02

Complex I (CI; NADH dehydrogenase) deficiency causes mitochondrial diseases, including Leigh syndrome. A variety of clinical symptoms of CI deficiency are known, including neurodegeneration. Here, we report an integrative study combining liquid chromatography-mass spectrometry (LC-MS)-based metabolome and proteome profiling in CI deficient HeLa cells. We report a rapid LC-MS-based method for the relative quantification of targeted metabolome profiling with an additional layer of confidence by applying multiple reaction monitoring (MRM) ion ratios for further identity confirmation and robustness. The proteome was analyzed by label-free quantification (LFQ). More than 6000 protein groups were identified. Pathway and network analyses revealed that the respiratory chain was highly deregulated, with metabolites such as FMN, FAD, NAD(+), and ADP, direct players of the OXPHOS system, and metabolites of the TCA cycle decreased up to 100-fold. Synthesis of functional iron-sulfur clusters, which are of central importance for the electron transfer chain, and degradation products like bilirubin were also significantly reduced. Glutathione metabolism on the pathway level, as well as individual metabolite components such as NADPH, glutathione (GSH), and oxidized glutathione (GSSG), was downregulated. Overall, metabolome and proteome profiles in CI deficient cells correlated well, supporting our integrated approach.

Mandibular Osteitis Fibrosa Cystica as First Sign of Vitamin D Deficiency

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Nour Mellouli

2018-01-01

Full Text Available Introduction. Brown tumors of hyperparathyroidism are locally destructive bone lesions. They are the late clinical consequence of the disease. They can occur in primary, secondary, and rarely tertiary forms. They affect usually long bones and less frequently those of the maxilla. Case Report. Our 45-year-old female patient presented with a mandibular tumor next to the first right lower molar. At first, we have chosen tooth extraction and tumor excision. When the histological report showed the giant cell tumor we suspected a metabolic bone disorder. Biochemical tests screened hyperparathyroidism and severe vitamin D deficiency, and parathyroid scintiscan revealed parathyroid adenoma. Discussion. The association of hyperparathyroidism and vitamin D deficiency leads to diagnostic uncertainty. First, secondary hyperparathyroidism can be due vitamin D deficiency. Second, data available show that vitamin D deficiency is more prevalent in patients with primary hyperparathyroidism than in general population. Hyperparathyroidism management is based on correct and precise diagnosis. Furthermore, the resolution of brown tumors depends on the cure of hyperparathyroidism. In fact, bone lesions should regress after biological tests’ normalization. Conclusion. Clinicians should be aware of such rare and complicated presentation. They must consider the diagnosis of the brown tumor to avoid extensive surgical excision and teeth extractions.

An Assessment of the Selenium Status of Iodine-Deficient and Non-Iodine Deficient Filipino Children

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Ma. Sofia Amarra

2002-06-01

Full Text Available The aim of this study is to examine and compare blood selenium levels in iodine-deficient and non-iodine deficient children. Two groups of children were examined: one group with iodine deficiency (n=31 and the other group with normal iodine status (n=32. Blood was extracted by venipuncture from children aged 6-10 years attending first grade in Commonwealth Elementary School in Quezon City. Whole blood selenium was examined by electrothermal atomic absorption spectrophotometry (AAS. Iodine status was determined by goiter palpation and urinary iodine excretion. Mean selenium levels of deficient and non-deficient children were compared using T-test. Using a cut-off value of 60 mg Se/L whole blood, the proportion of children with normal and deficient iodine status who fell below this cut-off was compared using chi-square test. Whole blood selenium values ranged from 17.6 to 133.6 mg/L. There were no significant differences in mean selenium levels between children with normal and deficient iodine status. Children with normal iodine status had a mean blood selenium level of 55.87 ± 26.3 mg/L while children with deficient iodine status had a mean level of 58.76 ± 26.4 mg/L. Sixty percent of children had blood selenium levels below the arbitrary cut-off of 60 mg/L with no significant difference between groups (p = 0.165, indicating that selenium deficiency is prevalent in this group of children regardless of iodine status. Since selenium deficiency limits the response to iodine supplementation, further investigation is needed to determine whether the same situation exists in children from other areas.

[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.

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 ...

Iron-Deficiency Anemia

Medline Plus

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 ...

Acid sphingomyelinase (aSMase) deficiency leads to abnormal microglia behavior and disturbed retinal function

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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.

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

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

Disturbed energy metabolism and muscular dystrophy caused by pure creatine deficiency are reversible by creatine intake

Science.gov (United States)

Nabuurs, C I; Choe, C U; Veltien, A; Kan, H E; van Loon, L J C; Rodenburg, R J T; Matschke, J; Wieringa, B; Kemp, G J; Isbrandt, D; Heerschap, A

2013-01-01

Creatine (Cr) plays an important role in muscle energy homeostasis by its participation in the ATP–phosphocreatine phosphoryl exchange reaction mediated by creatine kinase. Given that the consequences of Cr depletion are incompletely understood, we assessed the morphological, metabolic and functional consequences of systemic depletion on skeletal muscle in a mouse model with deficiency of l-arginine:glycine amidinotransferase (AGAT−/−), which catalyses the first step of Cr biosynthesis. In vivo magnetic resonance spectroscopy showed a near-complete absence of Cr and phosphocreatine in resting hindlimb muscle of AGAT−/− mice. Compared with wild-type, the inorganic phosphate/β-ATP ratio was increased fourfold, while ATP levels were reduced by nearly half. Activities of proton-pumping respiratory chain enzymes were reduced, whereas F1F0-ATPase activity and overall mitochondrial content were increased. The Cr-deficient AGAT−/− mice had a reduced grip strength and suffered from severe muscle atrophy. Electron microscopy revealed increased amounts of intramyocellular lipid droplets and crystal formation within mitochondria of AGAT−/− muscle fibres. Ischaemia resulted in exacerbation of the decrease of pH and increased glycolytic ATP synthesis. Oral Cr administration led to rapid accumulation in skeletal muscle (faster than in brain) and reversed all the muscle abnormalities, revealing that the condition of the AGAT−/− mice can be switched between Cr deficient and normal simply by dietary manipulation. Systemic creatine depletion results in mitochondrial dysfunction and intracellular energy deficiency, as well as structural and physiological abnormalities. The consequences of AGAT deficiency are more pronounced than those of muscle-specific creatine kinase deficiency, which suggests a multifaceted involvement of creatine in muscle energy homeostasis in addition to its role in the phosphocreatine–creatine kinase system. PMID:23129796

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.

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...

Diagnóstico diferencial da deficiência de ferro Differential diagnosis of iron deficiency

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Perla Vicari

2010-06-01

Full Text Available A deficiência de ferro é considerada a patologia hematológica mais prevalente no homem. Assim, é fundamental a adequada identificação de suas causas, bem como a diferenciação com outras patologias distintas para adequada abordagem da deficiência de ferro. Neste artigo são brevemente descritas outras condições que podem cursar com anemia microcítica, tais como: talassemias, anemia de doença crônica, anemia sideroblástica e envenenamento por chumbo, patologias estas que devem ser afastadas durante investigação de anemia ferropriva.Iron deficiency is considered to be the commonest hematological pathology in humans. Thus, the essential steps in an adequate approach of iron deficiency include: the proper identification of its causes and the differentiation between iron deficiency and other conditions. This article briefly describes other conditions that may present with microcytic anemia such as thalassemia, anemia of chronic diseases, sideroblastic anemia and lead intoxication. These diseases should be considered during the investigation of iron deficiency anemia.

Vitamin D-deficient osteomalacia due to excessive self-restrictions for atopic dermatitis.

Science.gov (United States)

Shikino, Kiyoshi; Ikusaka, Masatomi; Yamashita, Tomoko

2014-07-04

A 34-year-old Japanese woman presented with a 2-year history of generalised bone pain, muscle weakness and gait disturbance. The patient had been following a restricted diet (without fish or dairy products) and avoiding ultraviolet exposure for 8 years to manage her worsening atopic dermatitis. Physical examination revealed generalised bone tenderness and bilateral symmetric proximal muscle weakness. Vitamin D-deficient osteomalacia was diagnosed based on the laboratory examination findings, which indicated high serum alkaline phosphatase, high intact parathyroid hormone, and low 25-hydroxyvitamin D levels. Her symptoms improved after oral active vitamin D and calcium administration. To the best our knowledge, this case is the first report of vitamin D-deficient osteomalacia in an adult patient due to excessive dietary restriction for managing atopic dermatitis. We emphasise the importance of increasing awareness of vitamin D deficiency as a risk factor for the development of osteomalacia, and caution against excessive avoidance of sun exposure and dietary restriction. 2014 BMJ Publishing Group Ltd.

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....

Improving Effect Of Vitamin E Supplementation In Rats Suffering From Zinc Deficiency

International Nuclear Information System (INIS)

Matta, T.F.

2009-01-01

Vitamin E is a membrane-bound soluble lipid and naturally occurring antioxidant which protects animal tissues against oxidative damage. Several studies have suggested a possible interaction between zinc status and vitamin E in animals. The current investigation was conduced to elucidate the improving effect of vitamin E supplementation on some selected biochemical variables in the blood and tissues of albino rats suffering from zinc deficiency.Zinc deficiency was induced in rats by feeding male rats a low zinc diet for 6 weeks. Dietary vitamin E and zinc, separated or combined, were used to ameliorate the impacts of zinc deficiency in the last two weeks of the experiment. Fifty male albino rats weighing 70-80g in 5 equal groups were given for 6 weeks five semi purified diets different in their contents of vitamin E and zinc / kg diet as follows: Zn adequate diet (Zn =35 ppm) for group (I) served as control, Zn deficient diet (Zn = 3 ppm) for group (II), Zn deficient diet plus supplemental zinc (Zn = 84 ppm) for group (III), Zn deficient diet plus supplemental vitamin E (50 IU) for group (IV) and Zn deficient diet plus supplemental zinc and vitamin E (Zn = 84 ppm + i.p. 50 IU vitamin E) for group (V). Supplemental zinc and vitamin E were only given on the last two weeks of the experiment.The obtained results revealed that Zn deficiency led to a significant (P 4 , T 3 and testosterone levels were declined significantly in Zn deficient rats as well as a significant (P < 0.05) rise in TSH level as compared with their levels in the Zn deficient rats supplemented with Zn and vitamin E.In contrast, the concentration of serum total cholesterol (T.Chol) and triglycerides (TG) in Zn deficient rats were significantly increased than those recorded in control group. On the other hand, the activities of cytochrome P450 reductase and microsomal NADPH reductase were significantly decreased (P<0.05) in liver homogenates while significant increase was recorded in their corresponding

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

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

Congenital muscular dystrophy with merosin deficiency: MRI findings in five patients

Energy Technology Data Exchange (ETDEWEB)

Farina, L.; Milanesi, I.; Ciceri, E.; Savoiardo, M. [Dept. of Neuroradiology, Ist. Nazionale Neurologico C. Besta, Milan (Italy); Morandi, L.; Mora, M. [Dept. of Neuromuscular Disorders, Ist. Nazionale Neurologico C. Besta, Milan (Italy); Moroni, I.; Pantaleoni, C. [Dept. of Child Neurology, Ist. Nazionale Neurologico C. Besta, Milan (Italy)

1998-12-01

We present the MRI findings in five patients with congenital muscular dystrophy (CMD) and merosin (laminin {alpha} 2) deficiency, which was total in one and partial in four. In one patient with partial merosin deficiency, MRI was normal. The other four patients had supratentorial white matter abnormalities. In three, T2-weighted images revealed subcortical, deep lobar and periventricular high signal in white matter, while in the other there were only small peritrigonal areas of increased signal. On T1-weighted images, there was slightly low signal. Cortical abnormalities were absent. None of these changes were accompanied by symptoms or signs of central nervous system involvement. White matter abnormalities in a patient with CMD should prompt investigation of merosin. (orig.) With 4 figs., 11 refs.

Strategies to rescue the consequences of inducible arginase-1 deficiency in mice.

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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.

POTENTIAL DEFICIENCIES IN EDUCATION, INSTRUMENTATION, AND WARNINGS FOR LOCALLY GENERATED TSUNAMIS

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Daniel A. Walker

2010-01-01

Full Text Available A review of historical data for Hawaii reveals that significant tsunamis have been reported for only four of twenty-six potentially tsunamigenic earthquakes from 1868 through 2009 with magnitudes of 6.0 or greater. During the same time period, three significant tsunamis have been reported for substantially smaller earthquakes. This historical perspective, the fact that the last significant local tsunami occurred in 1975, and an understandable preoccupation with tsunamis generated around the margins of the Pacific, all combine to suggest apparent deficiencies in: (1 personal awareness of what to do in the event of a possible local tsunami; (2 the distribution of instrumentation capable of providing rapid confirmation that a local tsunami has been generated; and (3 the subsequent issuance of timely warnings for local tsunamis. With these deficiencies, far more lives may be lost in Hawaii due to local tsunamis than will result from tsunamis that have originated along the margins of the Pacific. Similar deficiencies may exist in other areas of the world threatened by local tsunamis.

Very long chain acyl-coenzyme A dehydrogenase deficiency with adult onset

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Smelt, A H; Poorthuis, B J; Onkenhout, W

1998-01-01

Very long chain acyl-coenzyme A (acyl-CoA) dehydrogenase (VLCAD) deficiency is a severe disorder of mitochondrial beta-oxidation in infants. We report adult onset of attacks of painful rhabdomyolysis. Gas chromatography identified strongly elevated levels of tetradecenoic acid, 14:1(n-9), tetrade......Very long chain acyl-coenzyme A (acyl-CoA) dehydrogenase (VLCAD) deficiency is a severe disorder of mitochondrial beta-oxidation in infants. We report adult onset of attacks of painful rhabdomyolysis. Gas chromatography identified strongly elevated levels of tetradecenoic acid, 14:1(n-9......), tetradecadienoic acid, 14:2(n-6), and hexadecadienoic acid, 16:2(n-6). Palmitoyl-CoA and behenoyl-CoA dehydrogenase in fibroblasts were deficient. Muscle VLCAD activity was very low. DNA analysis revealed compound heterozygosity for two missense mutations in the VLCAD gene. The relatively mild clinical course may...... be due to residual enzyme activity as a consequence of the two missense mutations. Treatment with L-carnitine and medium chain triglycerides in the diet did not reduce the attacks of rhabdomyolysis....

Simultaneous Left Ventricular and Deep Vein Thrombi Caused by Protein C Deficiency

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Harufumi Maki

2017-01-01

Full Text Available Protein C deficiency is a risk of venous thrombosis because of poor fibrinolytic activity. It remains controversial whether protein C deficiency causes arterial thrombosis. A 21-year-old woman was referred with a chief complaint of right leg pain and numbness. Contrast-enhanced computed tomography revealed a low-density mass in the left ventricle (LV, splenic infarction, and peripheral arterial obstructions in her right leg. Thrombosis extending from the renal vein to the inferior vena cava was also detected. Electrocardiography revealed ST depression in leads II, III, and aVF. Transthoracic echocardiography revealed hypokinesis of the apex and interventricular septum and a hypoechoic mass in the LV (26 × 20 mm. She was diagnosed with acute arterial obstruction caused by the LV thrombus, which might have resulted from previous myocardial infarction. Protein C activation turned out to be low (41% 5 days after admission. The anticoagulant therapy was switched from heparin to rivaroxaban 16 days after admission. The LV thrombus disappeared 24 days after initial treatment, and she has had no thrombotic episodes for 2.8 years under rivaroxaban therapy. Thrombophilia should be investigated for cases of simultaneous left ventricular and deep venous thrombi. Rivaroxaban can be effective in prevention of further thrombotic events.

The effects of micronutrient deficiencies on bacterial species from the human gut microbiota

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Hibberd, Matthew C. [Washington Univ. School of Medicine, St. Louis, MO (United States). Center for Genome Sciences and Systems Biology, Center for Gut Microbiome and Nutrition Research; Wu, Meng [Washington Univ. School of Medicine, St. Louis, MO (United States). Center for Genome Sciences and Systems Biology; Rodionov, Dmitry A. [Russian Academy of Sciences (RAS), Moscow (Russian Federation). A.A. Kharkevich Inst. for Information Transmission Problems; Sanford Burnham Prebys Medical Discovery Inst., La Jolla, CA (United States); Li, Xiaoqing [Sanford Burnham Prebys Medical Discovery Inst., La Jolla, CA (United States); Cheng, Jiye [Washington Univ. School of Medicine, St. Louis, MO (United States). Center for Genome Sciences and Systems Biology, Center for Gut Microbiome and Nutrition Researc; Griffin, Nicholas W. [Washington Univ. School of Medicine, St. Louis, MO (United States). Center for Genome Sciences and Systems Biology, Center for Gut Microbiome and Nutrition Researc; Barratt, Michael J. [Washington Univ. School of Medicine, St. Louis, MO (United States). Center for Genome Sciences and Systems Biology, Center for Gut Microbiome and Nutrition Researc; Giannone, Richard J. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Chemical Sciences Division; Hettich, Robert L. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States). Chemical Sciences Division; Osterman, Andrei L. [Sanford Burnham Prebys Medical Discovery Inst., La Jolla, CA (United States); Gordon, Jeffrey I. [Washington Univ. School of Medicine, St. Louis, MO (United States). Center for Genome Sciences and Systems Biology, Center for Gut Microbiome and Nutrition Researc

2017-05-17

Micronutrient deficiencies afflict two billion people. And while the impact of these imbalances on host biology has been studied extensively, much less is known about their effects on the developing or adult gut microbiota. Thus, we established a community of 44 cultured, sequenced human gut-derived bacterial species in gnotobiotic mice and fed the animals a defined, micronutrient-sufficient diet, followed by a derivative diet devoid of vitamin A, folate, iron or zinc, followed by return to the sufficient diet. Acute vitamin A deficiency had the largest effect on community structure and meta-transcriptome, with Bacteroides vulgatus, a prominent responder, increasing its abundance in the absence of vitamin A, and manifesting transcriptional changes involving various metabolic pathways. Applying retinol selection to a library of 30,300 B. vulgatus transposon mutants revealed that disruption of acrR abrogated retinol sensitivity. Genetic complementation studies, microbial RNA-Seq, and transcription factor binding assays disclosed that AcrR functions as a repressor of an adjacent AcrAB-TolC efflux system plus other members of its regulon. Retinol efflux measurements in wild-type, acrR-mutant, and complemented acrR mutant strains, plus treatment with a pharmacologic inhibitor of the efflux system, revealed that AcrAB-TolC is a determinant of retinol and bile acid sensitivity. We associated acute vitamin A deficiency with altered bile acid metabolism in vivo, raising the possibility that retinol, bile acid metabolites, and AcrAB-TolC interact to influence the fitness of B. vulgatus and perhaps other microbiota members. This type of preclinical model can help develop mechanistic insights about and more effective treatment strategies for micronutrient deficiencies.

Alterations of proteins in MDCK cells during acute potassium deficiency.

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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.

Hydrogen sulphide improves adaptation of Zea mays seedlings to iron deficiency.

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Chen, Juan; Wu, Fei-Hua; Shang, Yu-Ting; Wang, Wen-Hua; Hu, Wen-Jun; Simon, Martin; Liu, Xiang; Shangguan, Zhou-Ping; Zheng, Hai-Lei

2015-11-01

Hydrogen sulphide (H2S) is emerging as a potential molecule involved in physiological regulation in plants. However, whether H2S regulates iron-shortage responses in plants is largely unknown. Here, the role of H2S in modulating iron availability in maize (Zea mays L. cv Canner) seedlings grown in iron-deficient culture solution is reported. The main results are as follows: Firstly, NaHS, a donor of H2S, completely prevented leaf interveinal chlorosis in maize seedlings grown in iron-deficient culture solution. Secondly, electron micrographs of mesophyll cells from iron-deficient maize seedlings revealed plastids with few photosynthetic lamellae and rudimentary grana. On the contrary, mesophyll chloroplasts appeared completely developed in H2S-treated maize seedlings. Thirdly, H2S treatment increased iron accumulation in maize seedlings by changing the expression levels of iron homeostasis- and sulphur metabolism-related genes. Fourthly, phytosiderophore (PS) accumulation and secretion were enhanced by H2S treatment in seedlings grown in iron-deficient solution. Indeed, the gene expression of ferric-phytosiderophore transporter (ZmYS1) was specifically induced by iron deficiency in maize leaves and roots, whereas their abundance was decreased by NaHS treatment. Lastly, H2S significantly enhanced photosynthesis through promoting the protein expression of ribulose-1,5-bisphosphate carboxylase large subunit (RuBISCO LSU) and phosphoenolpyruvate carboxylase (PEPC) and the expression of genes encoding RuBISCO large subunit (RBCL), small subunit (RBCS), D1 protein (psbA), and PEPC in maize seedlings grown in iron-deficient solution. These results indicate that H2S is closely related to iron uptake, transport, and accumulation, and consequently increases chlorophyll biosynthesis, chloroplast development, and photosynthesis in plants. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Fetal deficiency of Lin28 programs life-long aberrations in growth and glucose metabolism

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Shinoda, Gen; Shyh-Chang, Ng; de Soysa, T. Yvanka; Zhu, Hao; Seligson, Marc T.; Shah, Samar P.; Abo-Sido, Nora; Yabuuchi, Akiko; Hagan, John P.; Gregory, Richard I.; Asara, John M.; Cantley, Lewis C.; Moss, Eric G.; Daley, George Q.

2013-01-01

LIN28A/B are RNA binding proteins implicated by genetic association studies in human growth and glucose metabolism. Mice with ectopic over-expression of Lin28a have shown related phenotypes. Here we describe the first comprehensive analysis of the physiologic consequences of Lin28a and Lin28b deficiency in knockout (KO) mice. Lin28a/b-deficiency led to dwarfism starting at different ages, and compound gene deletions showed a cumulative dosage effect on organismal growth. Conditional gene deletion at specific developmental stages revealed that fetal but neither neonatal nor adult deficiency resulted in growth defects and aberrations in glucose metabolism. Tissue-specific KO mice implicated skeletal muscle-deficiency in the abnormal programming of adult growth and metabolism. The effects of Lin28b KO can be rescued by Tsc1 haplo-insufficiency in skeletal muscles. Our data implicate fetal expression of Lin28a/b in the regulation of life-long effects on metabolism and growth, and demonstrate that fetal Lin28b acts at least in part via mTORC1 signaling. PMID:23666760

Molecular characterization of FXI deficiency.

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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.

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

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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.

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

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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.

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

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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.

Hemolysis, myopathy, and cardiac disease associated with hereditary phosphofructokinase deficiency in two Whippets

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Gerber, Karen; Harvey, John W.; D'Agorne, Sara; Wood, Jonathan; Giger, Urs

2009-01-01

Two male castrated Whippet littermates were presented at 1 year of age for pallor, tachycardia, systolic heart murmur, dark yellow to orange feces, intermittent lethargy, pigmenturia, and muscle shivering or cramping after exercise. Persistent macrocytic hypochromic anemia with marked reticulocytosis and metarubricytosis was found when CBC results were compared with reference values for Whippets. Increased serum creatine kinase activity and hyperkalemia also were sometimes present over the 4-year period of evaluation. Progressively increasing serum concentrations of N-terminal prohormone brain natriuretic peptide suggested cardiac disease. Erythrocytes from the whippets were less osmotically fragile but more alkaline fragile than those from control dogs. Erythrocyte phosphofructokinase (PFK) activities and 2,3-diphosphoglycerate concentrations were decreased. Restriction enzyme-based DNA test screening and DNA sequencing revealed the same mutation in the muscle-PFK gene of the Whippets as seen in English Springer Spaniel dogs with PFK deficiency. This is the first report of PFK deficiency in Whippet dogs. In addition to causing hemolysis and exertional myopathy, heart disease may be a prominent clinical component of PFK deficiency in this breed and has not been previously recognized in PFK-deficient English Springer Spaniels. PMID:19228357

Inducible arginase 1 deficiency in mice leads to hyperargininemia and altered amino acid metabolism.

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Yuan Yan Sin

Full Text Available Arginase deficiency is a rare autosomal recessive disorder resulting from a loss of the liver arginase isoform, arginase 1 (ARG1, which is the final step in the urea cycle for detoxifying ammonia. ARG1 deficiency leads to hyperargininemia, characterized by progressive neurological impairment, persistent growth retardation and infrequent episodes of hyperammonemia. Using the Cre/loxP-directed conditional gene knockout system, we generated an inducible Arg1-deficient mouse model by crossing "floxed" Arg1 mice with CreER(T2 mice. The resulting mice (Arg-Cre die about two weeks after tamoxifen administration regardless of the starting age of inducing the knockout. These treated mice were nearly devoid of Arg1 mRNA, protein and liver arginase activity, and exhibited symptoms of hyperammonemia. Plasma amino acid analysis revealed pronounced hyperargininemia and significant alterations in amino acid and guanidino compound metabolism, including increased citrulline and guanidinoacetic acid. Despite no alteration in ornithine levels, concentrations of other amino acids such as proline and the branched-chain amino acids were reduced. In summary, we have generated and characterized an inducible Arg1-deficient mouse model exhibiting several pathologic manifestations of hyperargininemia. This model should prove useful for exploring potential treatment options of ARG1 deficiency.

Changes in the transcriptomic profiles of maize roots in response to iron-deficiency stress.

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Li, Yan; Wang, Nian; Zhao, Fengtao; Song, Xuejiao; Yin, Zhaohua; Huang, Rong; Zhang, Chunqing

2014-07-01

Plants are often subjected to iron (Fe)-deficiency stress because of its low solubility. Plants have evolved two distinct strategies to solubilize and transport Fe to acclimate to this abiotic stress condition. Transcriptomic profiling analysis was performed using Illumina digital gene expression to understand the mechanism underlying resistance responses of roots to Fe starvation in maize, an important Strategy II plant. A total of 3,427, 4,069, 4,881, and 2,610 genes had significantly changed expression levels after Fe-deficiency treatments of 1, 2, 4 or 7 days, respectively. Genes involved in 2'-deoxymugineic acid (DMA) synthesis, secretion, and Fe(III)-DMA uptake were significantly induced. Many genes related to plant hormones, protein kinases, and protein phosphatases responded to Fe-deficiency stress, suggesting their regulatory roles in response to the Fe-deficiency stress. Functional annotation clustering analysis, using the Database for Annotation, Visualization and Integrated Discovery, revealed maize root responses to Fe starvation. This resulted in 38 functional annotation clusters: 25 for up-regulated genes, and 13 for down-regulated ones. These included genes encoding enzymes involved in the metabolism of carboxylic acids, isoprenoids and aromatic compounds, transporters, and stress response proteins. Our work provides integrated information for understanding maize response to Fe-deficiency stress.

Tool to manage Road Safety Deficiencies and risk of highway crashes

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Lopez Maldonado, G.; Baena Ruiz, L.; Garach Morcillo, L.; Oña Lopez, J. de

2016-07-01

In order to facilitate the management of the results obtained in the project “Analysis of the relationship between Road Safety Deficiencies, crashes and hazardous sections” financed by Public Works Agency of the Regional Government of Andalusia (AOPJA) and led by the research group TRYSE from University of Granada, a safety management tool has been developed. This application allows safety managers to consult some factors affecting crashes on two-lane rural highways.The main aim of that project was to analyze the influence of some road deficiencies on crashes and hazardous sections in the Complementary Road Network of Andalusia. These deficiencies were defined in a checklist and were identified by a road inspection. Decision Trees (DTs), that are a data mining technique that allows the extraction of Decision Rules (DRs), were used. DRs revealed the relationship between road deficiencies and crashes.The application allows two different analyses. A specific analysis of the Complementary Road Network of Andalusia, in which, particular safety problems can be identified, and the location of roads with those problems can be obtained. A more general analysis in which some characteristics related to road safety can be selected in order to know the combination of factors contributing to traffic crashes. Safety problems are based on data from Complementary Road Network of Andalusia but results can be extrapolated to other rural highways in Spain. (Author)

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...

Thymidine kinase 2 deficiency-induced mitochondrial DNA depletion causes abnormal development of adipose tissues and adipokine levels in mice.

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Joan Villarroya

Full Text Available Mammal adipose tissues require mitochondrial activity for proper development and differentiation. The components of the mitochondrial respiratory chain/oxidative phosphorylation system (OXPHOS are encoded by both mitochondrial and nuclear genomes. The maintenance of mitochondrial DNA (mtDNA is a key element for a functional mitochondrial oxidative activity in mammalian cells. To ascertain the role of mtDNA levels in adipose tissue, we have analyzed the alterations in white (WAT and brown (BAT adipose tissues in thymidine kinase 2 (Tk2 H126N knockin mice, a model of TK2 deficiency-induced mtDNA depletion. We observed respectively severe and moderate mtDNA depletion in TK2-deficient BAT and WAT, showing both tissues moderate hypotrophy and reduced fat accumulation. Electron microscopy revealed altered mitochondrial morphology in brown but not in white adipocytes from TK2-deficient mice. Although significant reduction in mtDNA-encoded transcripts was observed both in WAT and BAT, protein levels from distinct OXPHOS complexes were significantly reduced only in TK2-deficient BAT. Accordingly, the activity of cytochrome c oxidase was significantly lowered only in BAT from TK2-deficient mice. The analysis of transcripts encoding up to fourteen components of specific adipose tissue functions revealed that, in both TK2-deficient WAT and BAT, there was a consistent reduction of thermogenesis related gene expression and a severe reduction in leptin mRNA. Reduced levels of resistin mRNA were found in BAT from TK2-deficient mice. Analysis of serum indicated a dramatic reduction in circulating levels of leptin and resistin. In summary, our present study establishes that mtDNA depletion leads to a moderate impairment in mitochondrial respiratory function, especially in BAT, causes substantial alterations in WAT and BAT development, and has a profound impact in the endocrine properties of adipose tissues.

Thymidine kinase 2 deficiency-induced mitochondrial DNA depletion causes abnormal development of adipose tissues and adipokine levels in mice.

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Villarroya, Joan; Dorado, Beatriz; Vilà, Maya R; Garcia-Arumí, Elena; Domingo, Pere; Giralt, Marta; Hirano, Michio; Villarroya, Francesc

2011-01-01

Mammal adipose tissues require mitochondrial activity for proper development and differentiation. The components of the mitochondrial respiratory chain/oxidative phosphorylation system (OXPHOS) are encoded by both mitochondrial and nuclear genomes. The maintenance of mitochondrial DNA (mtDNA) is a key element for a functional mitochondrial oxidative activity in mammalian cells. To ascertain the role of mtDNA levels in adipose tissue, we have analyzed the alterations in white (WAT) and brown (BAT) adipose tissues in thymidine kinase 2 (Tk2) H126N knockin mice, a model of TK2 deficiency-induced mtDNA depletion. We observed respectively severe and moderate mtDNA depletion in TK2-deficient BAT and WAT, showing both tissues moderate hypotrophy and reduced fat accumulation. Electron microscopy revealed altered mitochondrial morphology in brown but not in white adipocytes from TK2-deficient mice. Although significant reduction in mtDNA-encoded transcripts was observed both in WAT and BAT, protein levels from distinct OXPHOS complexes were significantly reduced only in TK2-deficient BAT. Accordingly, the activity of cytochrome c oxidase was significantly lowered only in BAT from TK2-deficient mice. The analysis of transcripts encoding up to fourteen components of specific adipose tissue functions revealed that, in both TK2-deficient WAT and BAT, there was a consistent reduction of thermogenesis related gene expression and a severe reduction in leptin mRNA. Reduced levels of resistin mRNA were found in BAT from TK2-deficient mice. Analysis of serum indicated a dramatic reduction in circulating levels of leptin and resistin. In summary, our present study establishes that mtDNA depletion leads to a moderate impairment in mitochondrial respiratory function, especially in BAT, causes substantial alterations in WAT and BAT development, and has a profound impact in the endocrine properties of adipose tissues. © 2011 Villarroya et al.

Monocular Elevation Deficiency - Double Elevator Palsy

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... 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 ...

Genetics Home Reference: tyrosine hydroxylase deficiency

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... 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 ...

Deficiency in Cardiac Dystrophin Affects the Abundance of the α-/β-Dystroglycan Complex

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James Lohan

2005-01-01

Full Text Available Although Duchenne muscular dystrophy is primarily categorised as a skeletal muscle disease, deficiency in the membrane cytoskeletal protein dystrophin also affects the heart. The central transsarcolemmal linker between the actin membrane cytoskeleton and the extracellular matrix is represented by the dystrophin-associated dystroglycans. Chemical cross-linking analysis revealed no significant differences in the dimeric status of the α-/β-dystroglycan subcomplex in the dystrophic mdx heart as compared to normal cardiac tissue. In analogy to skeletal muscle fibres, heart muscle also exhibited a greatly reduced abundance of both dystroglycans in dystrophin-deficient cells. Immunoblotting demonstrated that the degree of reduction in α-dystroglycan is more pronounced in matured mdx skeletal muscle as contrasted to the mdx heart. The fact that the deficiency in dystrophin triggers a similar pathobiochemical response in both types of muscle suggests that the cardiomyopathic complications observed in x-linked muscular dystrophy might be initiated by the loss of the dystrophin-associated surface glycoprotein complex.

Mitochondrial DNA Depletion in Respiratory Chain–Deficient Parkinson Disease Neurons

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Rygiel, Karolina A.; Hepplewhite, Philippa D.; Morris, Christopher M.; Picard, Martin; Turnbull, Doug M.

2016-01-01

Objective To determine the extent of respiratory chain abnormalities and investigate the contribution of mtDNA to the loss of respiratory chain complexes (CI–IV) in the substantia nigra (SN) of idiopathic Parkinson disease (IPD) patients at the single‐neuron level. Methods Multiple‐label immunofluorescence was applied to postmortem sections of 10 IPD patients and 10 controls to quantify the abundance of CI–IV subunits (NDUFB8 or NDUFA13, SDHA, UQCRC2, and COXI) and mitochondrial transcription factors (TFAM and TFB2M) relative to mitochondrial mass (porin and GRP75) in dopaminergic neurons. To assess the involvement of mtDNA in respiratory chain deficiency in IPD, SN neurons, isolated with laser‐capture microdissection, were assayed for mtDNA deletions, copy number, and presence of transcription/replication‐associated 7S DNA employing a triplex real‐time polymerase chain reaction (PCR) assay. Results Whereas mitochondrial mass was unchanged in single SN neurons from IPD patients, we observed a significant reduction in the abundances of CI and II subunits. At the single‐cell level, CI and II deficiencies were correlated in patients. The CI deficiency concomitantly occurred with low abundances of the mtDNA transcription factors TFAM and TFB2M, which also initiate transcription‐primed mtDNA replication. Consistent with this, real‐time PCR analysis revealed fewer transcription/replication‐associated mtDNA molecules and an overall reduction in mtDNA copy number in patients. This effect was more pronounced in single IPD neurons with severe CI deficiency. Interpretation Respiratory chain dysfunction in IPD neurons not only involves CI, but also extends to CII. These deficiencies are possibly a consequence of the interplay between nDNA and mtDNA‐encoded factors mechanistically connected via TFAM. ANN NEUROL 2016;79:366–378 PMID:26605748

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

Common variable immune deficiency in a Pomeranian with Pneumocystis carinii pneumonia.

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Kanemoto, Hideyuki; Morikawa, Rei; Chambers, James Kenn; Kasahara, Koichi; Hanafusa, Yasuko; Uchida, Kazuyuki; Ohno, Koichi; Nakayama, Hiroyuki

2015-06-01

A Pomeranian dog, 1 year- and 8 month-old neutered female, was presented with persistent respiratory distress and recurrent generalized demodicosis. Physical examination revealed cyanosis, rough respiratory sounds, multifocal alopecia and dermal erosions on the dorsal side of the forelimbs, perineal area and skin around the eyes. A severe diffuse interstitial lung pattern was observed on thoracic radiographs. The blood examination revealed neutrophilia and hypoglobulinemia. Serum immunoglobulin concentrations of IgG and IgA were low. Histopathological examination revealed severe diffuse interstitial pneumonia with Pneumocystis carinii infection. Severe lymphoid depletion was observed in the spleen and other organs with lymphoid follicles consisted mainly of CD3-positive T cells and few cells of B-cell lineage. B-cell hypoplasia with subsequent antibody deficiency was suspected.

Genetics Home Reference: factor VII deficiency

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... 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 ...

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...

A case of myxedema coma caused by isolated thyrotropin stimulating hormone deficiency and Hashimoto's thyroiditis.

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Iida, Keiji; Hino, Yasuhisa; Ohara, Takeshi; Chihara, Kazuo

2011-01-01

Myxedema coma (MC) is a rare, but often fatal endocrine emergency. The majority of cases that occur in elderly women with long-standing primary hypothyroidism are caused by particular triggers. Conversely, MC of central origin is extremely rare. Here, we report a case of MC with both central and primary origins. A 56-year-old woman was transferred to our hospital due to loss of consciousness; a chest x-ray demonstrated severe cardiomegaly. Low body temperature, bradycardia, and pericardial effusion suggested the presence of hypothyroidism. Endocrinological examination revealed undetectable levels of serum free thyroxine (T(4)) and free triiodothyronine (T(3)), whereas serum thyroid-stimulating hormone (TSH) levels were not elevated. The woman's serum anti-thyroid peroxidase antibody and anti-thyroglobulin antibody tests were positive, indicating that she had Hashimoto's thyroiditis. Provocative tests to the anterior pituitary revealed that she had TSH and growth hormone (GH) deficiency; however, GH levels were restored after supplementation with levothyroxine for 5 months. This was not only a rare case of MC with TSH deficiency and Hashimoto's thyroiditis; the patient also developed severe osteoporosis and possessed transient elevated levels of serum carcinoembryonic antigen (CEA). This atypical case may suggest the role of anterior pituitary hormone deficiencies, as well as hypothyroidism, in the regulation of bone metabolism.

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

Prevalence of Iron Deficiency and Iron Deficiency Anemia in High-School Girl Students of Yazd

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M Noori Shadkam

2009-07-01

Full Text Available Introduction: It is generally assumed that 50% of the cases of anemia are due to iron deficiency. The most severe consequence of iron depletion is iron deficiency anemia (IDA, and it is still considered the most common nutrition deficiency worldwide. The main risk factors for IDA include: inadequate iron intake, impaired absorption or transport, physiologic losses associated with chronological or reproductive age, or acute or chronic blood loss, parasite infections such as hookworms, acute and chronic infections, including malaria, cancer, tuberculosis, HIV and other micronutrient deficiencies, including vitamins A and B12, folate, riboflavin, and copper deficiency. Methods: This work as a cross-sectional study was done in 2007-2008 in Yazd. Two hundred girls who participated in the study were selected randomly from eight girl high schools. Five ml venous blood was collected for determination of serum ferritin and cell blood count (CBC. Serum ferritin was determined by using ECLIA method and CBC by cell counter SYSMEX KX21N. Iron deficiency was defined as having serum ferritin values below 12 μ/l. Anemia was defined as having Hemoglobin levels below12 g/dl. Iron-deficiency anemia was considered to be the combination of both. Results: The3 mean ageyears and body mass index (kg/m2 were 15.19±0.7years and 21.5±4.2, respectively. Distribution in the 14, 15 and 16 years and more age groups were 13, 58.5 and 28.5 percent, respectively. Mean of Hemoglobin(g/dl, Hematocrit(%, MCV (fl, MCH (pg, MCHC (g/dl and ferritin(μ/l were 12.8±0.9, 38.9±3.0, 80.7±4.3, 26.6±1.8, 33.2±3.6 and 23±18.2, respectively. Of the total, 13.5% were anemic, 68% of which had Iron Deficiency Anemia (9.3% of the total. Iron deficiency was present in 34.7% of the population under study. Conclusion: According to world health organization criteria, anemia is a mild public health problem in this region, but iron deficiency is a significant problem and suitable measures for

Clinical significance of enzymatic deficiencies in the gastrointestinal tract with particular reference to lactase deficiency.

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Rossi, E; Lentze, M J

1984-12-01

The study of deficiencies of small intestinal brush-border hydrolases increased our knowledge about the specific functions of hydrolases in the digestion of smaller molecules on the microvillus surface of the absorptive cells. The sucrase-isomaltase (SI) complex has been shown to be synthesized as a precursor (pro-sucrase-isomaltase) which is then incorporated into the membrane. The hydrophobic N-terminal end of the molecule is anchored in the lipid bilayer. In SI deficiency the molecular base of the disease is still not clear. Absence of SI activity could be due to complete lack of precursor synthesis or to structural changes within the N-terminal end of the SI-complex. Deficiencies of peptide hydrolases have not been reported with the exception of enteropeptidase (EP). Here a congenital deficiency of the enzyme was observed as the primary defect in enzyme synthesis within the enterocytes and as a secondary defect due to exocrine pancreatic insufficiency. In contrast to the primary EP deficiency, the activity of EP can be restored in the cases of exocrine pancreatic insufficiency by treatment with pancreatic extracts. Primary lactase deficiency exists in various forms. Besides congenital lactase deficiency, the late onset or adult type of lactase deficiency has been observed. The latter occurs in many different ethnic groups around the world. Here, using gel electrophoresis and immunoelectrophoresis, the lack of enzyme activity could be shown to be a primary defect in enzyme protein synthesis. In man and in the rat, two different lactases have been identified. In contrast to adult lactase, fetal lactase contains sialic acid at the end of carbohydrate side chains.(ABSTRACT TRUNCATED AT 250 WORDS)

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

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... 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 ...

A Program for Iron Economy during Deficiency Targets Specific Fe Proteins.

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Hantzis, Laura J; Kroh, Gretchen E; Jahn, Courtney E; Cantrell, Michael; Peers, Graham; Pilon, Marinus; Ravet, Karl

2018-01-01

Iron (Fe) is an essential element for plants, utilized in nearly every cellular process. Because the adjustment of uptake under Fe limitation cannot satisfy all demands, plants need to acclimate their physiology and biochemistry, especially in their chloroplasts, which have a high demand for Fe. To investigate if a program exists for the utilization of Fe under deficiency, we analyzed how hydroponically grown Arabidopsis ( Arabidopsis thaliana ) adjusts its physiology and Fe protein composition in vegetative photosynthetic tissue during Fe deficiency. Fe deficiency first affected photosynthetic electron transport with concomitant reductions in carbon assimilation and biomass production when effects on respiration were not yet significant. Photosynthetic electron transport function and protein levels of Fe-dependent enzymes were fully recovered upon Fe resupply, indicating that the Fe depletion stress did not cause irreversible secondary damage. At the protein level, ferredoxin, the cytochrome- b 6 f complex, and Fe-containing enzymes of the plastid sulfur assimilation pathway were major targets of Fe deficiency, whereas other Fe-dependent functions were relatively less affected. In coordination, SufA and SufB, two proteins of the plastid Fe-sulfur cofactor assembly pathway, were also diminished early by Fe depletion. Iron depletion reduced mRNA levels for the majority of the affected proteins, indicating that loss of enzyme was not just due to lack of Fe cofactors. SufB and ferredoxin were early targets of transcript down-regulation. The data reveal a hierarchy for Fe utilization in photosynthetic tissue and indicate that a program is in place to acclimate to impending Fe deficiency. © 2018 American Society of Plant Biologists. All Rights Reserved.

IRF4 Deficiency Abrogates Lupus Nephritis Despite Enhancing Systemic Cytokine Production

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Lech, Maciej; Weidenbusch, Marc; Kulkarni, Onkar P.; Ryu, Mi; Darisipudi, Murthy Narayana; Susanti, Heni Eka; Mittruecker, Hans-Willi; Mak, Tak W.

2011-01-01

The IFN-regulatory factors IRF1, IRF3, IRF5, and IRF7 modulate processes involved in the pathogenesis of systemic lupus and lupus nephritis, but the contribution of IRF4, which has multiple roles in innate and adaptive immunity, is unknown. To determine a putative pathogenic role of IRF4 in lupus, we crossed Irf4-deficient mice with autoimmune C57BL/6-(Fas)lpr mice. IRF4 deficiency associated with increased activation of antigen-presenting cells in C57BL/6-(Fas)lpr mice, resulting in a massive increase in plasma levels of TNF and IL-12p40, suggesting that IRF4 suppresses cytokine release in these mice. Nevertheless, IRF4 deficiency completely protected these mice from glomerulonephritis and lung disease. The mice were hypogammaglobulinemic and lacked antinuclear and anti-dsDNA autoantibodies, revealing the requirement of IRF4 for the maturation of plasma cells. As a consequence, Irf4-deficient C57BL/6-(Fas)lpr mice neither developed immune complex disease nor glomerular activation of complement. In addition, lack of IRF4 impaired the maturation of Th17 effector T cells and reduced plasma levels of IL-17 and IL-21, which are cytokines known to contribute to autoimmune tissue injury. In summary, IRF4 deficiency enhances systemic inflammation and the activation of antigen-presenting cells but also prevents the maturation of plasma cells and effector T cells. Because these adaptive immune effectors are essential for the evolution of lupus nephritis, we conclude that IRF4 promotes the development of lupus nephritis despite suppressing antigen-presenting cells. PMID:21742731

Vitamin D Deficiency in Patients with Systemic Lupus Erythematosus

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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.

Selenium Deficiency Influences the mRNA Expression of Selenoproteins and Cytokines in Chicken Erythrocytes.

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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.

Telomerase-Deficient Mice Exhibit Bone Loss Owing to Defects in Osteoblasts and Increased Osteoclastogenesis by Inflammatory Microenvironment

DEFF Research Database (Denmark)

Saeed, H.; Abdallah, B. M.; Ditzel, N.

2011-01-01

Telomere shortening owing to telomerase deficiency leads to accelerated senescence of human skeletal (mesenchymal) stem cells (MSCs) in vitro, whereas overexpression leads to telomere elongation, extended life span, and enhanced bone formation. To study the role of telomere shortening in vivo, we...... studied the phenotype of telomerase-deficient mice (Terc(-/-)).Terc(-/-) mice exhibited accelerated age-related bone loss starting at 3 months of age and during 12 months of follow-up revealed by dual-energy X-ray absorptiometric (DXA) scanning and by micro-computed tomography (mu CT). Bone...... histomorphometry revealed decreased mineralized surface and bone-formation rate as well as increased osteoclast number and size in Terc(-/-) mice. Also, serum total deoxypyridinoline (tDPD) was increased in Terc(-/-) mice. MSCs and osteoprogenitors isolated from Terc(-l-) mice exhibited intrinsic defects...

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

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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.

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

Kernicterus by glucose-6-phosphate dehydrogenase deficiency: a case report and review of the literature

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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.

Enhancing dopaminergic signaling and histone acetylation promotes long-term rescue of deficient fear extinction

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Whittle, N; Maurer, V; Murphy, C; Rainer, J; Bindreither, D; Hauschild, M; Scharinger, A; Oberhauser, M; Keil, T; Brehm, C; Valovka, T; Striessnig, J; Singewald, N

2016-01-01

Extinction-based exposure therapy is used to treat anxiety- and trauma-related disorders; however, there is the need to improve its limited efficacy in individuals with impaired fear extinction learning and to promote greater protection against return-of-fear phenomena. Here, using 129S1/SvImJ mice, which display impaired fear extinction acquisition and extinction consolidation, we revealed that persistent and context-independent rescue of deficient fear extinction in these mice was associated with enhanced expression of dopamine-related genes, such as dopamine D1 (Drd1a) and -D2 (Drd2) receptor genes in the medial prefrontal cortex (mPFC) and amygdala, but not hippocampus. Moreover, enhanced histone acetylation was observed in the promoter of the extinction-regulated Drd2 gene in the mPFC, revealing a potential gene-regulatory mechanism. Although enhancing histone acetylation, via administering the histone deacetylase (HDAC) inhibitor MS-275, does not induce fear reduction during extinction training, it promoted enduring and context-independent rescue of deficient fear extinction consolidation/retrieval once extinction learning was initiated as shown following a mild conditioning protocol. This was associated with enhanced histone acetylation in neurons of the mPFC and amygdala. Finally, as a proof-of-principle, mimicking enhanced dopaminergic signaling by L-dopa treatment rescued deficient fear extinction and co-administration of MS-275 rendered this effect enduring and context-independent. In summary, current data reveal that combining dopaminergic and epigenetic mechanisms is a promising strategy to improve exposure-based behavior therapy in extinction-impaired individuals by initiating the formation of an enduring and context-independent fear-inhibitory memory. PMID:27922638

Vitamin B12 deficiency presenting as acute ataxia.

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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.

Zinc: physiology, deficiency, and parenteral nutrition.

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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.

Citrin deficiency: a novel cause of failure to thrive that responds to a high-protein, low-carbohydrate diet.

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Dimmock, David; Kobayashi, Keiko; Iijima, Mikio; Tabata, Ayako; Wong, Lee-Jun; Saheki, Takeyori; Lee, Brendan; Scaglia, Fernando

2007-03-01

The proband was born at 36 weeks, appropriate for gestational age, to nonconsanguineous white parents. There was no evidence of hyperbilirubinemia or intrahepatic cholestasis in the neonatal period, and she had normal newborn screen results. She presented with 3 episodes of life-threatening bleeding and anemia. The diagnostic evaluation for her bleeding diathesis revealed an abnormal clotting profile with no biochemical evidence for hepatocellular damage. She was incidentally noted to have severe growth deceleration that failed to respond to 502 kJ/kg (120 kcal/kg) per day of protein-hydrolyzed formula. An extensive diagnostic workup for failure to thrive, which was otherwise normal, included plasma amino acid analysis that revealed hyperglutaminemia and citrulline levels within the reference range. Testing of a repeat sample revealed isolated hypercitrullinemia. No argininosuccinic acid was detected. Her ammonia level and urine orotic acid were within the reference ranges. Subsequent plasma amino acid analysis exhibited a profile suggestive of neonatal intrahepatic cholestasis caused by citrin deficiency with elevations in citrulline, methionine, and threonine. Western blotting of fibroblasts demonstrated citrin deficiency, and a deletion for exon 3 was found in the patient's coding DNA of the SLC25A13 gene. On the basis of the experience with adults carrying this condition, the patient was given a high-protein, low-carbohydrate diet. The failure to thrive and bleeding diathesis resolved. When compliance with the dietary prescription was relaxed, growth deceleration was again noted, although significant bleeding did not recur. This is the first report of an infant of Northern European descent with citrin deficiency. The later age at presentation with failure to thrive and bleeding diathesis and without obvious evidence of neonatal intrahepatic cholestasis expands the clinical spectrum of citrin deficiency. This case emphasizes the importance of continued dietary

High Prevalence of Vitamin B12 Deficiency and No Folate Deficiency in Young Children in Nepal

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Bernadette N. Ng’eno

2017-01-01

Full Text Available Many children in low- and middle-income countries may have inadequate intake of vitamin B12 and folate; data confirming these inadequacies are limited. We used biochemical, demographic, behavioral and anthropometric data to describe the folate and vitamin B12 concentrations among six- to 23-month-old Nepalese children. Vitamin B12 (serum B12 < 150 pmol/L and folate deficiencies (red blood cell (RBC folate < 226.5 nmol/L were assessed. We used logistic regression to identify predictors of vitamin B12 deficiency. The vitamin B12 geometric mean was 186 pmol/L; 30.2% of children were deficient. The mean RBC folate concentration was 13,612 nmol/L; there was no deficiency. Factors associated with vitamin B12 deficiency included: (a age six to 11 months (adjusted odds ratio (aOR 1.51; 95% confidence interval (CI: 1.18, 1.92 or 12–17 months (aOR 1.38; 95% CI: 1.10, 1.72 compared to 18–23 months; (b being stunted (aOR 1.24; 95% CI: 1.03, 1.50 compared to not being stunted; (c and not eating animal-source foods (aOR 1.85; 95% CI: 1.42, 2.41 compared to eating animal-source foods the previous day. There was a high prevalence of vitamin B12 deficiency, but no folate deficiency. Improving early feeding practices, including the consumption of rich sources of vitamin B12, such as animal-source foods and fortified foods, may help decrease deficiency.

MutLα heterodimers modify the molecular phenotype of Friedreich ataxia.

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Vahid Ezzatizadeh

Full Text Available Friedreich ataxia (FRDA, the most common autosomal recessive ataxia disorder, is caused by a dynamic GAA repeat expansion mutation within intron 1 of FXN gene, resulting in down-regulation of frataxin expression. Studies of cell and mouse models have revealed a role for the mismatch repair (MMR MutS-heterodimer complexes and the PMS2 component of the MutLα complex in the dynamics of intergenerational and somatic GAA repeat expansions: MSH2, MSH3 and MSH6 promote GAA repeat expansions, while PMS2 inhibits GAA repeat expansions.To determine the potential role of the other component of the MutLα complex, MLH1, in GAA repeat instability in FRDA, we have analyzed intergenerational and somatic GAA repeat expansions from FXN transgenic mice that have been crossed with Mlh1 deficient mice. We find that loss of Mlh1 activity reduces both intergenerational and somatic GAA repeat expansions. However, we also find that loss of either Mlh1 or Pms2 reduces FXN transcription, suggesting different mechanisms of action for Mlh1 and Pms2 on GAA repeat expansion dynamics and regulation of FXN transcription.Both MutLα components, PMS2 and MLH1, have now been shown to modify the molecular phenotype of FRDA. We propose that upregulation of MLH1 or PMS2 could be potential FRDA therapeutic approaches to increase FXN transcription.

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.

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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.

Increased susceptibility to Yersinia enterocolitica Infection of Tff2 deficient mice.

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Shah, Aftab A; Mihalj, Martina; Ratkay, Ivana; Lubka-Pathak, Maria; Balogh, Peter; Klingel, Karin; Bohn, Erwin; Blin, Nikolaus; Baus-Loncar, Mirela

2012-01-01

TFF2 is one of the members of the trefoil factor family, known for its role in protection of gastrointestinal epithelia upon injury; however, recent studies suggest that TFF2 could also play an important role in the immune system. In the present study Tff2 deficient and wild type mice were infected by Y. enterocolitica which resulted in a lethal outcome in all Tff2 deficient mice, but not in WT animals. Yersinia invaded Peyer's patches more efficiently as shown by high bacterial titers in the KO mice while wild type mice displayed lower titers and a visible bacterial accumulation in the intestine. Bacterial accumulation in Peyer's patches of Tff2 deficient mice was accompanied by increased recruitment of macrophages. While an increased level of MAC-1 positive cells was observed in the spleens of both Tff2 deficient and WT mice at third day post infection, bacterial dissemination to liver, lung and kidneys was observed only in Tff2 knock-out mice. Analysis of the cellular composition of spleen did not reveal any substantial alteration to WT animals, suggesting possible disregulation of hemopoietic cells involved in immune response to Y. enterocolitica. These new data indicate that Tff2 plays an important role in immune response by protecting the organism from consequences of infection and that Tff2 knock-out mice react adversely to bacterial infections, in this case specifically to Y. enterocolitica. Copyright © 2012 S. Karger AG, Basel.

Dietary Selenium Deficiency Exacerbates DSS-Induced Epithelial Injury and AOM/DSS-Induced Tumorigenesis

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Barrett, Caitlyn W.; Singh, Kshipra; Motley, Amy K.; Lintel, Mary K.; Matafonova, Elena; Bradley, Amber M.; Ning, Wei; Poindexter, Shenika V.; Parang, Bobak; Reddy, Vishruth K.; Chaturvedi, Rupesh; Fingleton, Barbara M.; Washington, Mary K.; Wilson, Keith T.; Davies, Sean S.; Hill, Kristina E.; Burk, Raymond F.; Williams, Christopher S.

2013-01-01

Selenium (Se) is an essential micronutrient that exerts its functions via selenoproteins. Little is known about the role of Se in inflammatory bowel disease (IBD). Epidemiological studies have inversely correlated nutritional Se status with IBD severity and colon cancer risk. Moreover, molecular studies have revealed that Se deficiency activates WNT signaling, a pathway essential to intestinal stem cell programs and pivotal to injury recovery processes in IBD that is also activated in inflammatory neoplastic transformation. In order to better understand the role of Se in epithelial injury and tumorigenesis resulting from inflammatory stimuli, we examined colonic phenotypes in Se-deficient or -sufficient mice in response to dextran sodium sulfate (DSS)-induced colitis, and azoxymethane (AOM) followed by cyclical administration of DSS, respectively. In response to DSS alone, Se-deficient mice demonstrated increased morbidity, weight loss, stool scores, and colonic injury with a concomitant increase in DNA damage and increases in inflammation-related cytokines. As there was an increase in DNA damage as well as expression of several EGF and TGF-β pathway genes in response to inflammatory injury, we sought to determine if tumorigenesis was altered in the setting of inflammatory carcinogenesis. Se-deficient mice subjected to AOM/DSS treatment to model colitis-associated cancer (CAC) had increased tumor number, though not size, as well as increased incidence of high grade dysplasia. This increase in tumor initiation was likely due to a general increase in colonic DNA damage, as increased 8-OHdG staining was seen in Se-deficient tumors and adjacent, non-tumor mucosa. Taken together, our results indicate that Se deficiency worsens experimental colitis and promotes tumor development and progression in inflammatory carcinogenesis. PMID:23861820

π-Extended Isoindigo-Based Derivative: A Promising Electron-Deficient Building Block for Polymer Semiconductors.

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Xu, Long; Zhao, Zhiyuan; Xiao, Mingchao; Yang, Jie; Xiao, Jian; Yi, Zhengran; Wang, Shuai; Liu, Yunqi

2017-11-22

The exploration of novel electron-deficient building blocks is a key task for developing high-performance polymer semiconductors in organic thin-film transistors. In view of the situation of the lack of strong electron-deficient building blocks, we designed two novel π-extended isoindigo-based electron-deficient building blocks, IVI and F 4 IVI. Owing to the strong electron-deficient nature and the extended π-conjugated system of the two acceptor units, their copolymers, PIVI2T and PF 4 IVI2T, containing 2,2'-bithiophene donor units, are endowed with deep-lying highest occupied molecular orbital (HOMO)/lowest unoccupied molecular orbital (LUMO) energy levels and strong intermolecular interactions. In comparison to PIVI2T, the fluorinated PF 4 IVI2T exhibits stronger intra- and intermolecular interactions, lower HOMO/LUMO energy levels up to -5.74/-4.17 eV, and more ordered molecular packing with a smaller π-π stacking distance of up to 3.53 Å, resulting in an excellent ambipolar transporting behavior and a promising application in logic circuits for PF 4 IVI2T in ambient with hole and electron mobilities of up to 1.03 and 1.82 cm 2 V -1 s -1 , respectively. The results reveal that F 4 IVI is a promising and strong electron-deficient building unit to construct high-performance semiconducting polymers, which provides an insight into the structure-property relationships for the exploration and molecular engineering of excellent electron-deficient building blocks in the field of organic electronics.

Familial glucocorticoid deficiency presenting with generalized hyperpigmentation in an Egyptian child: a case report

Directory of Open Access Journals (Sweden)

Metwalley Kotb A

2012-04-01

Full Text Available Abstract Introduction Familial glucocorticoid deficiency, or hereditary unresponsiveness to adrenocorticotropic hormone, is a rare autosomal recessive disease characterized by glucocorticoid deficiency in the absence of mineralocorticoid deficiency. It may present in infancy or early childhood with hyperpigmentation, failure to thrive, recurrent infections, hypoglycemic attacks and convulsions that may result in coma or death. Here, we report the case of an 18-month-old Egyptian boy with familial glucocorticoid deficiency. Case presentation An 18-month-old Egyptian boy was referred to our institution for evaluation of generalized hyperpigmentation of the body associated with recurrent convulsions; one of his siblings, who had died at the age of nine months, also had generalized hyperpigmentation of the body. The initial clinical examination revealed generalized symmetrical deep hyperpigmentation of the body as well as hypotonia, normal blood pressure and normal male genitalia. He had low blood glucose and cortisol levels, normal aldosterone and high adrenocorticotropic hormone levels. Based on the above mentioned data, a provisional diagnosis of familial glucocorticoid deficiency was made, which was confirmed by a molecular genetics study. Oral hydrocortisone treatment at a dose of 10 mg/m2/day was started. The child was followed up after two months of treatment; the hyperpigmentation has lessened in comparison with his initial presentation and his blood sugar and cortisol levels were normalized. Conclusion Familial glucocorticoid deficiency is a rare, treatable disease that can be easily missed due to nonspecific presentations. The consequences of delayed diagnosis and treatment are associated with high rates of morbidity and mortality.

Use of genotype-environment interactions to elucidate the pattern of maize root plasticity to nitrogen deficiency.

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Li, Pengcheng; Zhuang, Zhongjuan; Cai, Hongguang; Cheng, Shuai; Soomro, Ayaz Ali; Liu, Zhigang; Gu, Riliang; Mi, Guohua; Yuan, Lixing; Chen, Fanjun

2016-03-01

Maize (Zea mays L.) root morphology exhibits a high degree of phenotypic plasticity to nitrogen (N) deficiency, but the underlying genetic architecture remains to be investigated. Using an advanced BC4 F3 population, we investigated the root growth plasticity under two contrasted N levels and identified the quantitative trait loci (QTLs) with QTL-environment (Q × E) interaction effects. Principal components analysis (PCA) on changes of root traits to N deficiency (ΔLN-HN) showed that root length and biomass contributed for 45.8% in the same magnitude and direction on the first PC, while root traits scattered highly on PC2 and PC3. Hierarchical cluster analysis on traits for ΔLN-HN further assigned the BC4 F3 lines into six groups, in which the special phenotypic responses to N deficiency was presented. These results revealed the complicated root plasticity of maize in response to N deficiency that can be caused by genotype-environment (G × E) interactions. Furthermore, QTL mapping using a multi-environment analysis identified 35 QTLs for root traits. Nine of these QTLs exhibited significant Q × E interaction effects. Taken together, our findings contribute to understanding the phenotypic and genotypic pattern of root plasticity to N deficiency, which will be useful for developing maize tolerance cultivars to N deficiency. © 2015 Institute of Botany, Chinese Academy of Sciences.

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 ...

Vitamin D/dietary calcium deficiency rickets and pseudo-vitamin D deficiency rickets

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Glorieux, Francis H; Pettifor, John M

2014-01-01

This review describes the pathogenesis, clinical presentation and biochemical perturbations found in privational (nutritional) rickets and pseudo-vitamin D deficiency rickets (PDDR), an autosomal recessive condition with loss of function mutations in CYP27B1. It may seem strange to combine a discussion on privational rickets and PDDR as a single topic, but privational rickets and PDDR present with similar clinical signs and symptoms and with similar perturbations in bone and mineral metabolism. Of interest is the characteristic lack of features of rickets at birth in infants with PDDR, a finding which has also been reported in infants born to vitamin D-deficient mothers. This highlights the independence of the fetus and neonate from the need for vitamin D to maintain calcium homeostasis during this period. The variable roles of vitamin D deficiency and dietary calcium deficiency in the pathogenesis of privational rickets are discussed and the associated alterations in vitamin D metabolism highlighted. Although PDDR is a rare autosomal recessive disorder, results of long-term follow-up are now available on the effect of treatment with calcitriol, and these are discussed. Areas of uncertainty, such as should affected mothers breastfeed their infants, are emphasized. PMID:24818008

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)....

Isolated sulfite oxidase deficiency.

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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.

Prevalence of high blood pressure, heart disease, thalassemia, sickle-cell anemia, and iron-deficiency anemia among the UAE adolescent population.

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Barakat-Haddad, Caroline

2013-01-01

This study examined the prevalence of high blood pressure, heart disease, and medical diagnoses in relation to blood disorders, among 6,329 adolescent students (age 15 to 18 years) who reside in the United Arab Emirates (UAE). Findings indicated that the overall prevalence of high blood pressure and heart disease was 1.8% and 1.3%, respectively. Overall, the prevalence for thalassemia, sickle-cell anemia, and iron-deficiency anemia was 0.9%, 1.6%, and 5%, respectively. Bivariate analysis revealed statistically significant differences in the prevalence of high blood pressure among the local and expatriate adolescent population in the Emirate of Sharjah. Similarly, statistically significant differences in the prevalence of iron-deficiency anemia were observed among the local and expatriate population in Abu Dhabi city, the western region of Abu Dhabi, and Al-Ain. Multivariate analysis revealed the following significant predictors of high blood pressure: residing in proximity to industry, nonconventional substance abuse, and age when smoking or exposure to smoking began. Ethnicity was a significant predictor of heart disease, thalassemia, sickle-cell anemia, and iron-deficiency anemia. In addition, predictors of thalassemia included gender (female) and participating in physical activity. Participants diagnosed with sickle-cell anemia and iron-deficiency anemia were more likely to experience different physical activities.

Iron deficiency in blood donors

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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.

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...

Thymidine kinase 2 and alanyl-tRNA synthetase 2 deficiencies cause lethal mitochondrial cardiomyopathy: case reports and review of the literature.

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Mazurova, Stella; Magner, Martin; Kucerova-Vidrova, Vendula; Vondrackova, Alzbeta; Stranecky, Viktor; Pristoupilova, Anna; Zamecnik, Josef; Hansikova, Hana; Zeman, Jiri; Tesarova, Marketa; Honzik, Tomas

2017-07-01

Cardiomyopathy is a common manifestation in neonates and infants with mitochondrial disorders. In this study, we report two cases manifesting with fatal mitochondrial hypertrophic cardiomyopathy, which include the third known patient with thymidine kinase 2 deficiency and the ninth patient with alanyl-tRNA synthetase 2 deficiency. The girl with thymidine kinase 2 deficiency had hypertrophic cardiomyopathy together with regression of gross motor development at the age of 13 months. Neurological symptoms and cardiac involvement progressed into severe myopathy, psychomotor arrest, and cardiorespiratory failure at the age of 22 months. The imaging methods and autoptic studies proved that she suffered from unique findings of leucoencephalopathy, severe, mainly cerebellar neuronal degeneration, and hepatic steatosis. The girl with alanyl-tRNA synthetase 2 deficiency presented with cardiac failure and underlying hypertrophic cardiomyopathy within 12 hours of life and subsequently died at 9 weeks of age. Muscle biopsy analyses demonstrated respiratory chain complex I and IV deficiencies, and histological evaluation revealed massive mitochondrial accumulation and cytochrome c oxidase-negative fibres in both cases. Exome sequencing in the first case revealed compound heterozygozity for one novel c.209T>C and one previously published c.416C>T mutation in the TK2 gene, whereas in the second case homozygozity for the previously described mutation c.1774C>T in the AARS2 gene was determined. The thymidine kinase 2 mutations resulted in severe mitochondrial DNA depletion (to 12% of controls) in the muscle. We present, for the first time, severe leucoencephalopathy and hepatic steatosis in a patient with thymidine kinase 2 deficiency and the finding of a ragged red fibre-like image in the muscle biopsy in a patient with alanyl-tRNA synthetase 2 deficiency.

Iron deficiency and hematinic deficiencies in atrial fibrillation: A new insight into comorbidities.

Science.gov (United States)

Keskin, Muhammed; Ural, Dilek; Altay, Servet; Argan, Onur; Börklü, Edibe Betül; Kozan, Ömer

2018-03-01

Iron deficiency (ID) is the most common nutritional deficiency, and iron metabolism becomes further deteriorated in the presence of certain conditions, such as heart failure (HF). Atrial fibrillation (AF) has many similarities to HF, including a chronic inflammatory pathophysiology; however, the prevalence of ID and other hematinic deficiencies in AF patients have not been determined. In this study, the prevalence of iron (serum ferritin <100 µg/L or ferritin 100-299 µg/L with transferrin saturation <20%), vitamin B12 (<200 pg/mL), and folate deficiency (<4.0 ng/mL) was evaluated in 101 patients with non-valvular AF with preserved left ventricular ejection fraction and no signs of HF, and the results were compared with 35 age- and gender-matched controls. Anemia was detected in 26% of the patients. A total of 48 (47.6%) patients had ID, 10 (9.9%) had a vitamin B12 deficiency, and 13 (12.9%) had a folate deficiency. The prevalence of ID was similar in the controls and the paroxysmal AF patients, but increased gradually in persistent and permanent AF. Univariate logistic regression analysis demonstrated that permanent vs. paroxysmal AF [Odds ratio (OR): 2.17; 95% confidence interval (CI): 0.82-5.69; p=0.011], high sensitive C-reactive protein (OR: 1.47; 95% CI: 0.93-2.36; p=0.019), N-terminal pro b-type natriuretic peptide (OR: 1.24; 95% CI: 0.96-1.71; p=0.034), and white blood cell count (OR: 1.21; 95% CI: 0.95-1.58; p=0.041) were associated with ID. In multivariable analysis, permanent AF remained as an independent clinical associate of ID (OR: 4.30; 95% CI: 0.83-12.07; p=0.039). ID is common in permanent AF, as in HF. Inflammation and neurohormonal activation seem to contribute to its development.

Genetics Home Reference: X-linked creatine deficiency

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... 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 ...

Genetics Home Reference: carnitine-acylcarnitine translocase deficiency

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... 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 ...

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.

Adipocyte Glucocorticoid Receptor Deficiency Attenuates Aging- and HFD-Induced Obesity and Impairs the Feeding-Fasting Transition.

Science.gov (United States)

Mueller, Kristina M; Hartmann, Kerstin; Kaltenecker, Doris; Vettorazzi, Sabine; Bauer, Mandy; Mauser, Lea; Amann, Sabine; Jall, Sigrid; Fischer, Katrin; Esterbauer, Harald; Müller, Timo D; Tschöp, Matthias H; Magnes, Christoph; Haybaeck, Johannes; Scherer, Thomas; Bordag, Natalie; Tuckermann, Jan P; Moriggl, Richard

2017-02-01

Glucocorticoids (GCs) are important regulators of systemic energy metabolism, and aberrant GC action is linked to metabolic dysfunctions. Yet, the extent to which normal and pathophysiological energy metabolism depend on the GC receptor (GR) in adipocytes remains unclear. Here, we demonstrate that adipocyte GR deficiency in mice significantly impacts systemic metabolism in different energetic states. Plasma metabolomics and biochemical analyses revealed a marked global effect of GR deficiency on systemic metabolite abundance and, thus, substrate partitioning in fed and fasted states. This correlated with a decreased lipolytic capacity of GR-deficient adipocytes under postabsorptive and fasting conditions, resulting from impaired signal transduction from β-adrenergic receptors to adenylate cyclase. Upon prolonged fasting, the impaired lipolytic response resulted in abnormal substrate utilization and lean mass wasting. Conversely, GR deficiency attenuated aging-/diet-associated obesity, adipocyte hypertrophy, and liver steatosis. Systemic glucose tolerance was improved in obese GR-deficient mice, which was associated with increased insulin signaling in muscle and adipose tissue. We conclude that the GR in adipocytes exerts central but diverging roles in the regulation of metabolic homeostasis depending on the energetic state. The adipocyte GR is indispensable for the feeding-fasting transition but also promotes adiposity and associated metabolic disorders in fat-fed and aged mice. © 2017 by the American Diabetes Association.

Slitrk1-deficient mice display elevated anxiety-like behavior and noradrenergic abnormalities.

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Katayama, K; Yamada, K; Ornthanalai, V G; Inoue, T; Ota, M; Murphy, N P; Aruga, J

2010-02-01

Mutations in SLITRK1 are found in patients with Tourette's syndrome and trichotillomania. SLITRK1 encodes a transmembrane protein containing leucine-rich repeats that is produced predominantly in the nervous system. However, the role of this protein is largely unknown, except that it can modulate neurite outgrowth in vitro. To clarify the role of Slitrk1 in vivo, we developed Slitrk1-knockout mice and analyzed their behavioral and neurochemical phenotypes. Slitrk1-deficient mice exhibited elevated anxiety-like behavior in the elevated plus-maze test as well as increased immobility time in forced swimming and tail suspension tests. Neurochemical analysis revealed that Slitrk1-knockout mice had increased levels of norepinephrine and its metabolite 3-methoxy-4-hydroxyphenylglycol. Administration of clonidine, an alpha2-adrenergic agonist that is frequently used to treat patients with Tourette's syndrome, attenuated the anxiety-like behavior of Slitrk1-deficient mice in the elevated plus-maze test. These results lead us to conclude that noradrenergic mechanisms are involved in the behavioral abnormalities of Slitrk1-deficient mice. Elevated anxiety due to Slitrk1 dysfunction may contribute to the pathogenesis of neuropsychiatric diseases such as Tourette's syndrome and trichotillomania.

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.)

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.).

Genetics Home Reference: CDKL5 deficiency disorder

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... 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 ...

Remedial early numeracy education: can children identified as having a language deficiency benefit?

Science.gov (United States)

Van Luit, Johannes E H; Toll, Sylke W M

2015-01-01

Growing attention has been paid to the possibility of supporting early numeracy in at-risk kindergartners. Furthermore, it is assumed that language proficiency is an important prerequisite in early maths skills. To examine whether remedial early numeracy education in kindergarten, which has been proven to be effective in general, is also beneficial for children with a language deficiency. Based on intensive selection, four different conditions were included: two groups received remedial education, one consisting of children being language proficient (N = 86) and one of children with a language deficiency (N = 26), and two groups followed the regular curriculum, one consisting of children being language proficient (N = 51) and one of children with a language deficiency (N = 24). Remedial education was for 1.5 school years (90 sessions, 30 min per session, twice per week), following the programme 'The Road to Mathematics'. During this period, the children receiving remedial education did not attend the regular maths lessons in the classroom, which were offered for at least 1 h per week. Effects were assessed for early numeracy and mathematical skills (operationalized as basic calculation fluency) in kindergarten and first grade. Three analyses of covariance (ANCOVAs) revealed that, when accounting for achievement at pre-test, children with a language deficiency who received remedial numeracy education performed better on early numeracy skills in kindergarten and first grade than kindergartners with a language deficiency that followed the regular curriculum. Furthermore, they were able to catch up with their language proficient peers in early numeracy. However, children with a language deficiency who received remedial numeracy education did not differ from children who followed the regular curriculum on mathematical skills, suggesting that benefits for numeracy did not generalize to more advanced skills of addition and subtraction. Since, in general, it can be

Environmental stresses of field growth allow cinnamyl alcohol dehydrogenase-deficient Nicotiana attenuata plants to compensate for their structural deficiencies.

Science.gov (United States)

Kaur, Harleen; Shaker, Kamel; Heinzel, Nicolas; Ralph, John; Gális, Ivan; Baldwin, Ian T

2012-08-01

The organized lignocellulosic assemblies of cell walls provide the structural integrity required for the large statures of terrestrial plants. Silencing two CINNAMYL ALCOHOL DEHYDROGENASE (CAD) genes in Nicotiana attenuata produced plants (ir-CAD) with thin, red-pigmented stems, low CAD and sinapyl alcohol dehydrogenase activity, low lignin contents, and rubbery, structurally unstable stems when grown in the glasshouse (GH). However, when planted into their native desert habitat, ir-CAD plants produced robust stems that survived wind storms as well as the wild-type plants. Despite efficient silencing of NaCAD transcripts and enzymatic activity, field-grown ir-CAD plants had delayed and restricted spread of red stem pigmentation, a color change reflecting blocked lignification by CAD silencing, and attained wild-type-comparable total lignin contents. The rubbery GH phenotype was largely restored when field-grown ir-CAD plants were protected from wind, herbivore attack, and ultraviolet B exposure and grown in restricted rooting volumes; conversely, it was lost when ir-CAD plants were experimentally exposed to wind, ultraviolet B, and grown in large pots in growth chambers. Transcript and liquid chromatography-electrospray ionization-time-of-flight analysis revealed that these environmental stresses enhanced the accumulation of various phenylpropanoids in stems of field-grown plants; gas chromatography-mass spectrometry and nuclear magnetic resonance analysis revealed that the lignin of field-grown ir-CAD plants had GH-grown comparable levels of sinapaldehyde and syringaldehyde cross-linked into their lignins. Additionally, field-grown ir-CAD plants had short, thick stems with normal xylem element traits, which collectively enabled field-grown ir-CAD plants to compensate for the structural deficiencies associated with CAD silencing. Environmental stresses play an essential role in regulating lignin biosynthesis in lignin-deficient plants.

Decreased autophosphorylation of EGF receptor in insulin-deficient diabetic rats

International Nuclear Information System (INIS)

Okamoto, M.; Kahn, C.R.; Maron, R.; White, M.F.

1988-01-01

The authors have previously reported that despite an increase in receptor concentration, there is a decrease in autophosphorylation and tyrosine kinase activity of the insulin receptor in insulin-deficient diabetic rats. To determine if other tyrosine kinases might be altered, they have studied the epidermal growth factor (EGF) receptor kinase in wheat germ agglutinin-purified, Triton X-100-solubilized liver membranes from streptozotocin (STZ)-induced diabetic rats and the insulin-deficient BB rat. They find that autophosphorylation of EGF receptor is decreased in proportion to the severity of the diabetic state in STZ rats with a maximal decrease of 67%. A similar decrease in autophosphorylation was observed in diabetic BB rats that was partially normalized by insulin treatment. Separation of tryptic phosphopeptides by reverse-phase high-performance liquid chromatography revealed a decrease in labeling at all sites of autophosphorylation. A parallel decrease in EGF receptor phosphorylation was also found by immunoblotting with an antiphosphotyrosine antibody. EGF receptor concentration, determined by Scatchard analysis of 125 I-labeled EGF binding, was decreased by 39% in the STZ rat and 27% in the diabetic BB rat. Thus autophosphorylation of EGF receptor, like that of the insulin receptor, is decreased in insulin-deficient rat liver. In the case of EGF receptor, this is due in part to a decrease in receptor number and in part to a decrease in the specific activity of the kinase

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 ...

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 ...

The "multiple hormone deficiency" theory of aging: is human senescence caused mainly by multiple hormone deficiencies?

Science.gov (United States)

Hertoghe, T

2005-12-01

In the human body, the productions, levels and cell receptors of most hormones progressively decline with age, gradually putting the body into various states of endocrine deficiency. The circadian cycles of these hormones also change, sometimes profoundly, with time. In aging individuals, the well-balanced endocrine system can fall into a chaotic condition with losses, phase-advancements, phase delays, unpredictable irregularities of nycthemeral hormone cycles, in particular in very old or sick individuals. The desynchronization makes hormone activities peak at the wrong times and become inefficient, and in certain cases health threatening. The occurrence of multiple hormone deficits and spilling through desynchronization may constitute the major causes of human senescence, and they are treatable causes. Several arguments can be put forward to support the view that senescence is mainly a multiple hormone deficiency syndrome: First, many if not most of the signs, symptoms and diseases (including cardiovascular diseases, cancer, obesity, diabetes, osteoporosis, dementia) of senescence are similar to physical consequences of hormone deficiencies and may be caused by hormone deficiencies. Second, most of the presumed causes of senescence such as excessive free radical formation, glycation, cross-linking of proteins, imbalanced apoptosis system, accumulation of waste products, failure of repair systems, deficient immune system, may be caused or favored by hormone deficiencies. Even genetic causes such as limits to cell proliferation (such as the Hayflick limit of cell division), poor gene polymorphisms, premature telomere shortening and activation of possible genetic "dead programs" may have links with hormone deficiencies, being either the consequence, the cause, or the major favoring factor of hormone deficiencies. Third, well-dosed and -balanced hormone supplements may slow down or stop the progression of signs, symptoms, or diseases of senescence and may often

FANCD2 Maintains Fork Stability in BRCA1/2-Deficient Tumors and Promotes Alternative End-Joining DNA Repair

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Zeina Kais

2016-06-01

Full Text Available BRCA1/2 proteins function in homologous recombination (HR-mediated DNA repair and cooperate with Fanconi anemia (FA proteins to maintain genomic integrity through replication fork stabilization. Loss of BRCA1/2 proteins results in DNA repair deficiency and replicative stress, leading to genomic instability and enhanced sensitivity to DNA-damaging agents. Recent studies have shown that BRCA1/2-deficient tumors upregulate Polθ-mediated alternative end-joining (alt-EJ repair as a survival mechanism. Whether other mechanisms maintain genomic integrity upon loss of BRCA1/2 proteins is currently unknown. Here we show that BRCA1/2-deficient tumors also upregulate FANCD2 activity. FANCD2 is required for fork protection and fork restart in BRCA1/2-deficient tumors. Moreover, FANCD2 promotes Polθ recruitment at sites of damage and alt-EJ repair. Finally, loss of FANCD2 in BRCA1/2-deficient tumors enhances cell death. These results reveal a synthetic lethal relationship between FANCD2 and BRCA1/2, and they identify FANCD2 as a central player orchestrating DNA repair pathway choice at the replication fork.

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.

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.

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.

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.

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

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.

Hypocalcemia and tetany caused by vitamin D deficiency in a child with intestinal lymphangiectasia.

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Lu, Ying-Yi; Wu, Jia-Feng; Ni, Yen-Hsuan; Peng, Steven Shinn-Forng; Shun, Chia-Tung; Chang, Mei-Hwei

2009-10-01

Primary intestinal lymphangiectasia is a rare disease of children, which is characterized by chronic diarrhea and complicated with malnutrition, including fat-soluble vitamin deficiency. We report a girl aged 4 years and 8 months who was diagnosed with the disease by endoscopic duodenal biopsy at 8 months of age. She presented initially with chronic diarrhea at 4 months of age. Generalized edema with hypoalbuminemia frequently occurred despite regular albumin supplements. Multiple vitamins initially were not supplied regularly. Episodes of tetany caused by hypocalcemia developed 4 years after the diagnosis of intestinal lymphangiectasia. Imaging study (long-bone X-ray and dual-energy X-ray absorptiometry) revealed low bone density. Complicated vitamin D deficiency [low serum 25-hydroxy vitamin D concentration (intestinal lymphangiectasia.

Prekallikrein Deficiency Presenting as Recurrent Cerebrovascular Accident: Case Report and Review of the Literature

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Esteban Uribe Bojanini

2012-01-01

Full Text Available We report the case of a woman with history of hypertension and hyperlipidemia presenting with recurrent episodes consistent clinically with cerebrovascular accidents (CVA, and MRI changes suggestive of ischemia versus vasculitis as their cause. No anatomical neurological, rheumatic, cardioembolic, or arteriosclerotic etiologies could be determined by extensive workup. Incidentally, the patient was found to have prolonged activated Partial Thromboplastin Time (aPTT and a normal Prothrombin Time (PT; further testing revealed a prekallikrein deficiency. Since no other cause for the CVAs was established, and other prothrombotic states were ruled out, it is proposed that they are clinical manifestations derived from the prekallikrein deficiency, which in a patient with known cardiovascular risk factors could lead to thrombotic complications such as stroke.

Dopamine beta-hydroxylase deficiency

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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.

Mood disorder with mixed, psychotic features due to vitamin b12 deficiency in an adolescent: case report

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Tufan Ali

2012-06-01

Full Text Available Abstract Vitamin B12 is one of the essential vitamins affecting various systems of the body. Reports of psychiatric disorders due to its deficiency mostly focus on middle aged and elderly patients. Here we report a case of vitamin B 12 deficiency in a 16-year old, male adolescent who presented with mixed mood disorder symptoms with psychotic features. Chief complaints were “irritability, regressive behavior, apathy, crying and truancy” which lasted for a year. Premorbid personality was unremarkable with no substance use/exposure or infections. No stressors were present. The patient was not vegetarian. Past medical history and family history was normal. Neurological examination revealed glossitis, ataxia, rigidity in both shoulders, cog-wheel rigidity in the left elbow, bilateral problems of coordination in cerebellar examination, reduced swinging of the arms and masked face. Romberg’s sign was present. Laboratory evaluations were normal. Endoscopy and biopsy revealed atrophy of the gastric mucosa with Helicobacter Pylori colonization. Schilling test was suggestive of malabsorbtion. He was diagnosed with Mood disorder with Mixed, Psychotic Features due to Vitamin B12 Deficiency and risperidone 0.5 mg/day and intramuscular vitamin B12 500 mcg/day were started along with referral for treatment of Helicobacter pylori. A visit on the second week revealed no psychotic features. Romberg’s sign was negative and cerebellar tests were normal. Extrapyramidal symptoms were reduced while Vitamin B12 levels were elevated. Risperidone was stopped and parenteral Vitamin B12 treatment was continued with monthly injections for 3 months. Follow-up endoscopy and biopsy at the first month demonstrated eradication of H. pylori. He was followed monthly for another 6 months and psychiatric symptoms did not recur at the time of last evaluation. Despite limitations, this case may underline the observation that mood disorders with psychotic features

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

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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.

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...

Increased glucose dependence in resting, iron-deficient rats

International Nuclear Information System (INIS)

Brooks, G.A.; Henderson, S.A.; Dallman, P.R.

1987-01-01

Rates of blood glucose and lactate turnover were assessed in resting iron-deficient and iron-sufficient (control) rats to test the hypothesis that dependence on glucose metabolism is increased in iron deficiency. Male Sprague-Dawley rats, 21 days old, were fed a diet containing either 6 mg iron/kg feed (iron-deficient group) or 50 mg iron/kg feed (iron-sufficient group) for 3-4 wk. The iron-deficient group became anemic, with hemoglobin levels of 6.4 ± 0.2 compared with 13.8 ± 0.3 g/dl for controls. Rats received a 90-min primed continuous infusion of D-[6- 3 H]glucose and sodium L-[U- 14 C]lactate via a jugular catheter. Serial samples were taken from a carotid catheter for concentration and specific activity determinations. Iron-deficient rats had significantly higher blood glucose and lactate concentrations than controls. The iron-deficient group had a significantly higher glucose turnover rate than the control group. Significantly more metabolite recycling in iron-deficient rats was indicated by greater incorporation of 14 C into blood glucose. Assuming a carbon crossover correction factor of 2, half of blood glucose arose from lactate in deficient animals. By comparison, only 25% of glucose arose from lactate in controls. Lack of a difference in lactate turnover rates between deficient rats and controls was attributed to 14 C recycling. The results indicate a greater dependence on glucose metabolism in iron-deficient rats

Constitutional mismatch repair deficiency presenting in childhood as three simultaneous malignancies.

Science.gov (United States)

Walter, Andrew W; Ennis, Sara; Best, Hunter; Vaughn, Cecily P; Swensen, Jeffrey J; Openshaw, Amanda; Gripp, Karen W

2013-11-01

A 13-year-old child presented with three simultaneous malignancies: glioblastoma multiforme, Burkitt lymphoma, and colonic adenocarcinoma. She was treated for her diseases without success and died 8 months after presentation. Genetic analysis revealed a homozygous mutation in the PMS2 gene, consistent with constitutional mismatch repair deficiency. Her siblings and parents were screened: three of four siblings and both parents were heterozygous for this mutation; the fourth sibling did not have the mutation. Copyright © 2013 Wiley Periodicals, Inc.

Analysis of B chromosome nondisjunction induced by the r-X1 deficiency in maize.

Science.gov (United States)

Tseng, Shih-Hsuan; Peng, Shu-Fen; Cheng, Ya-Ming

2017-11-20

The maize B chromosome typically undergoes nondisjunction during the second microspore division. For normal A chromosomes, the r-X1 deficiency in maize can induce nondisjunction during the second megaspore and first microspore divisions. However, it is not known whether the r-X1 deficiency also induces nondisjunction of the maize B chromosome during these cell divisions. To answer this question, chromosome numbers were determined in the progeny of r-X1/R-r female parents carrying two B chromosomes. Some of the r-X1-lacking progeny (21.2%) contained zero or two B chromosomes. However, a much higher percentage of the r-X1-containing progeny (43.4%) exhibited zero or two B chromosomes, but none displayed more than two B chromosomes. Thus, the results indicated that the r-X1 deficiency could also induce nondisjunction of the B chromosome during the second megaspore division; moreover, the B chromosome in itself could undergo nondisjunction during the same division. In addition, pollen grains from plants with two B chromosomes lacking or exhibiting the r-X1 deficiency were compared via pollen fluorescence in situ hybridization (FISH) using a B chromosome-specific probe. The results revealed that the r-X1 deficiency could induce the occurrence of B chromosome nondisjunction during the first microspore division and that the B chromosome in itself could undergo nondisjunction during the same division at a lower frequency. Our data shed more light on the behavior of the maize B chromosome during cell division.

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...

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

Reticulocyte maturity indices in iron deficiency anemia

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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.

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.

Acquired multiple Acyl-CoA dehydrogenase deficiency in 10 horses with atypical myopathy.

Science.gov (United States)

Westermann, C M; Dorland, L; Votion, D M; de Sain-van der Velden, M G M; Wijnberg, I D; Wanders, R J A; Spliet, W G M; Testerink, N; Berger, R; Ruiter, J P N; van der Kolk, J H

2008-05-01

The aim of the current study was to assess lipid metabolism in horses with atypical myopathy. Urine samples from 10 cases were subjected to analysis of organic acids, glycine conjugates, and acylcarnitines revealing increased mean excretion of lactic acid, ethylmalonic acid, 2-methylsuccinic acid, butyrylglycine, (iso)valerylglycine, hexanoylglycine, free carnitine, C2-, C3-, C4-, C5-, C6-, C8-, C8:1-, C10:1-, and C10:2-carnitine as compared with 15 control horses (12 healthy and three with acute myopathy due to other causes). Analysis of plasma revealed similar results for these predominantly short-chain acylcarnitines. Furthermore, measurement of dehydrogenase activities in lateral vastus muscle from one horse with atypical myopathy indeed showed deficiencies of short-chain acyl-CoA dehydrogenase (0.66 as compared with 2.27 and 2.48 in two controls), medium-chain acyl-CoA dehydrogenase (0.36 as compared with 4.31 and 4.82 in two controls) and isovaleryl-CoA dehydrogenase (0.74 as compared with 1.43 and 1.61 nmol min(-1) mg(-1) in two controls). A deficiency of several mitochondrial dehydrogenases that utilize flavin adenine dinucleotide as cofactor including the acyl-CoA dehydrogenases of fatty acid beta-oxidation, and enzymes that degrade the CoA-esters of glutaric acid, isovaleric acid, 2-methylbutyric acid, isobutyric acid, and sarcosine was suspected in 10 out of 10 cases as the possible etiology for a highly fatal and prevalent toxic equine muscle disease similar to the combined metabolic derangements seen in human multiple acyl-CoA dehydrogenase deficiency also known as glutaric acidemia type II.

Bone pain and extremely low bone mineral density due to severe vitamin D deficiency in celiac disease

NARCIS (Netherlands)

Rabelink, N.M.; Westgeest, H.M.; Bravenboer, N.; Jacobs, M.A.J.M.; Lips, P.T.A.M.

2011-01-01

Case report A 29-year-old wheelchair-bound woman was presented to us by the gastroenterologist with suspected osteomalacia. She had lived in the Netherlands all her life and was born of Moroccan parents. Her medical history revealed iron deficiency, growth retardation, and celiac disease, for which

Differences of Excess and Deficiency Zheng in Patients with Chronic Hepatitis B by Urinary Metabonomics

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Shujun Sun

2013-01-01

Full Text Available Traditional Chinese medicine (TCM physicians stratify patients with the same disease into different subtypes in order to guide the appropriate treatment, which is called Zheng (TCM syndrome classification. Excess and deficiency ZHENG is a couple of basic ZHENGs of maladjusted body nature, reflecting the struggling state of human body and pathogenic factor and is important and prevalently exists in the ZHENG classification of many diseases. The present work using chronic hepatitis B (CHB as an entry point explored the substance connotation of excess and deficiency ZHENG with the metabonomic technology based on gas chromatography-mass spectrometry (GC-MS. The different substantial basis of two ZHENGs suggested that CHB patients could be categorized into two groups with diverse pathogenesis. The differential metabolites and disturbed pathways compared to not-obvious ZHENG characters patients (without ZHENG group/WZ were selected in both of the two ZHENGs. The ROC analysis demonstrated that five metabolites had a greater potential to be the clinic biomarkers of EZ or DZ. And excess ZHENG revealed a higher level of immune function than deficiency ZHENG. We are eager to transform the concept of traditional excess and deficiency ZHENGs to modern therapeutic approaches, with the prospect to help to promote personalized medicine.

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.

ATP Synthase Deficiency due to TMEM70 Mutation Leads to Ultrastructural Mitochondrial Degeneration and Is Amenable to Treatment

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Anne K. Braczynski

2015-01-01

Full Text Available TMEM70 is involved in the biogenesis of mitochondrial ATP synthase and mutations in the TMEM70 gene impair oxidative phosphorylation. Herein, we report on pathology and treatment of ATP synthase deficiency in four siblings. A consanguineous family of Roma (Gipsy ethnic origin gave birth to 6 children of which 4 were affected presenting with dysmorphic features, failure to thrive, cardiomyopathy, metabolic crises, and 3-methylglutaconic aciduria as clinical symptoms. Genetic testing revealed a homozygous mutation (c.317-2A>G in the TMEM70 gene. While light microscopy was unremarkable, ultrastructural investigation of muscle tissue revealed accumulation of swollen degenerated mitochondria with lipid crystalloid inclusions, cristae aggregation, and exocytosis of mitochondrial material. Biochemical analysis of mitochondrial complexes showed an almost complete ATP synthase deficiency. Despite harbouring the same mutation, the clinical outcome in the four siblings was different. Two children died within 60 h after birth; the other two had recurrent life-threatening metabolic crises but were successfully managed with supplementation of anaplerotic amino acids, lipids, and symptomatic treatment during metabolic crisis. In summary, TMEM70 mutations can cause distinct ultrastructural mitochondrial degeneration and almost complete deficiency of ATP synthase but are still amenable to treatment.

Fulminant lipid storage myopathy due to multiple acyl-coenzyme a dehydrogenase deficiency.

Science.gov (United States)

Whitaker, Charles H; Felice, Kevin J; Silvers, David; Wu, Qian

2015-08-01

The lipid storage myopathies, primary carnitine deficiency, neutral lipid storage disease, and multiple acyl coenzyme A dehydrogenase deficiency (MADD), are progressive disorders that cause permanent weakness. These disorders of fatty acid metabolism and intracellular triglyceride degradation cause marked fat deposition and damage to muscle cells. We describe a rapidly progressive myopathy in a previously healthy 33-year-old woman. Over 4 months, she developed a proximal and axial myopathy associated with diffuse myalgia and dysphagia, ultimately leading to respiratory failure and death. Muscle biopsy showed massive accumulation of lipid. Plasma acylcarnitine and urine organic acid analysis was consistent with MADD. This was confirmed by molecular genetic testing, which revealed 2 pathogenic mutations in the ETFDH gene. This report illustrates a late-onset case of MADD and reviews the differential diagnosis and evaluation of patients with proximal myopathy and excessive accumulation of lipid on muscle biopsy. © 2014 Wiley Periodicals, Inc.

Retinal venous thrombosis in a young patient with coagulation factor XII deficiency.

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Borrego-Sanz, L; Santos-Bueso, E; Sáenz-Francés, F; Martínez-de-la-Casa, J M; García-Feijoo, J; Gegúndez-Fernández, J A; García-Sánchez, J

2014-08-01

A 35-year-old woman, with no relevant medical history, was referred for sudden vision loss in the left eye. Ophthalmological examination showed best corrected visual acuity of 1.0 in the right eye and 0.3 in left eye, with normal anterior pole and intraocular pressure. Fundus examination of the left eye revealed a venous thrombosis in the superior temporal branch, with dilated and tortuous retinal veins. The patient was referred to the hematology unit for thrombophilia study, and was diagnosed with a coagulation XII or Hageman factor deficiency. The development of retinal vessel occlusions, in patients under 50 years of age, is frequently associated with thrombophilia or hypercoagulability disorders. Factor XII deficiency is a rare condition, and its presence could contribute to a higher risk of thromboembolic events. Copyright © 2013 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

Behavioral impairments in animal models for zinc deficiency

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Simone eHagmeyer

2015-01-01

Full Text Available Apart from teratogenic and pathological effects of zinc deficiency such as the occurrence of skin lesions, anorexia, growth retardation, depressed wound healing, altered immune function, impaired night vision, and alterations in taste and smell acuity, characteristic behavioral changes in animal models and human patients suffering from zinc deficiency have been observed. Given that it is estimated that about 17% of the worldwide population are at risk for zinc deficiency and that zinc deficiency is associated with a variety of brain disorders and disease states in humans, it is of major interest to investigate, how these behavioral changes will affect the individual and a putative course of a disease. Thus, here, we provide a state of the art overview about the behavioral phenotypes observed in various models of zinc deficiency, among them environmentally produced zinc deficient animals as well as animal models based on a genetic alteration of a particular zinc homeostasis gene. Finally, we compare the behavioral phenotypes to the human condition of mild to severe zinc deficiency and provide a model, how zinc deficiency that is associated with many neurodegenerative and neuropsychological disorders might modify the disease pathologies.

Carbohydrate metabolism in erythrocytes of copper deficient rats.

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Brooks, S P J; Cockell, K A; Dawson, B A; Ratnayake, W M N; Lampi, B J; Belonje, B; Black, D B; Plouffe, L J

2003-11-01

Dietary copper deficiency is known to adversely affect the circulatory system of fructose-fed rats. Part of the problem may lie in the effect of copper deficiency on intermediary metabolism. To test this, weanling male Long-Evans rats were fed for 4 or 8 weeks on sucrose-based diets containing low or adequate copper content. Copper deficient rats had significantly lower plasma and tissue copper as well as lower plasma copper, zinc-superoxide dismutase activity. Copper deficient rats also had a significantly higher heart:body weight ratio when compared to pair-fed controls. Direct measurement of glycolysis and pentose phosphate pathway flux in erythrocytes using (13)C NMR showed no differences in carbon flux from glucose or fructose to pyruvate but a significantly higher flux through the lactate dehydrogenase locus in copper deficient rats (approximately 1.3 times, average of glucose and glucose + fructose measurements). Copper-deficient animals had significantly higher erythrocyte concentrations of glucose, fructose, glyceraldehyde 3-phosphate and NAD(+). Liver metabolite levels were also affected by copper deficiency being elevated in glycogen and fructose 1-phosphate content. The results show small changes in carbohydrate metabolism of copper deficient rats.

Sleep transitions in hypocretin-deficient narcolepsy.

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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.

Loss of synaptic zinc transport in progranulin deficient mice may contribute to progranulin-associated psychopathology and chronic pain.

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Hardt, Stefanie; Heidler, Juliana; Albuquerque, Boris; Valek, Lucie; Altmann, Christine; Wilken-Schmitz, Annett; Schäfer, Michael K E; Wittig, Ilka; Tegeder, Irmgard

2017-11-01

Affective and cognitive processing of nociception contributes to the development of chronic pain and vice versa, pain may precipitate psychopathologic symptoms. We hypothesized a higher risk for the latter with immanent neurologic diseases and studied this potential interrelationship in progranulin-deficient mice, which are a model for frontotemporal dementia, a disease dominated by behavioral abnormalities in humans. Young naïve progranulin deficient mice behaved normal in tests of short-term memory, anxiety, depression and nociception, but after peripheral nerve injury, they showed attention-deficit and depression-like behavior, over-activity, loss of shelter-seeking, reduced impulse control and compulsive feeding behavior, which did not occur in equally injured controls. Hence, only the interaction of 'pain x progranulin deficiency' resulted in the complex phenotype at young age, but neither pain nor progranulin deficiency alone. A deep proteome analysis of the prefrontal cortex and olfactory bulb revealed progranulin-dependent alterations of proteins involved in synaptic transport, including neurotransmitter transporters of the solute carrier superfamily. In particular, progranulin deficiency was associated with a deficiency of nuclear and synaptic zinc transporters (ZnT9/Slc30a9; ZnT3/Slc30a3) with low plasma zinc. Dietary zinc supplementation partly normalized the attention deficit of progranulin-deficient mice, which was in part reminiscent of autism-like and compulsive behavior of synaptic zinc transporter Znt3-knockout mice. Hence, the molecular studies point to defective zinc transport possibly contributing to progranulin-deficiency-associated psychopathology. Translated to humans, our data suggest that neuropathic pain may precipitate cognitive and psychopathological symptoms of an inherent, still silent neurodegenerative disease. Copyright © 2017. Published by Elsevier B.V.

Spontaneous chondroma formation in CD2-Cre-driven Erk-deficient mice.

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Shiokawa, Moe; Lu, Xiuyuan; Miyake, Yasunobu; Ishikawa, Eri; Pagès, Gilles; Pouysségur, Jacques; Ogata, Masato; Yamasaki, Sho

2017-12-18

Lineage-specific Cre Tg mice are widely used to delineate the functions of genes in a tissue-specific manner. Several T-cell-specific promoter cassettes have been developed; however, the activities of those promoters in non-T cells have not been investigated extensively. Here, we report that CD2-Cre-mediated deletion of Erk proteins by generating CD2-Cre × Erk1-/-Erk2flox/flox (Erk∆CD2-Cre) mice results in abnormal cartilage hyperplasia. Histological analysis revealed that this abnormality is caused by aberrant hyperplasia of chondrocytes. The presence of Erk-deficient T cells is not required for this chondroma formation, as it was similarly observed in the absence of T cells in a CD3ε-deficient background. In addition, adoptive transfer of bone marrow cells from Erk∆CD2-Cre mice to wild-type recipients did not cause chondroma formation, suggesting that Erk-deficient non-immune cells are responsible for this abnormality. By tracing Cre-expressed tissues using a ROSA26-STOP-RFP allele, we found that the chondroma emitted RFP fluorescence, indicating that functional Cre is expressed in hyperplastic chondrocytes in Erk∆CD2-Cre mice. Furthermore, RFP+ chondrocytes were also found in an Erk-sufficient background, albeit without aberrant growth. These results suggest that unexpected expression of CD2-driven Cre in chondrocytes generates Erk-deficient chondrocytes, resulting in hyperplastic cartilage formation. Recently, two independent reports showed that CD4-Cre-mediated Ras-Erk signaling ablation led to similar abnormal cartilage formation (Guittard, G., Gallardo, D. L., Li, W. et al. 2017. Unexpected cartilage phenotype in CD4-Cre-conditional SOS-deficient mice. Front. Immunol. 8:343; Wehenkel, M., Corr, M., Guy, C. S. et al. 2017. Extracellular signal-regulated kinase signaling in CD4-expressing cells inhibits osteochondromas. Front. Immunol. 8:482). Together with these reports, our study suggests that an unexpected link exists between T-like cell and

Genetics Home Reference: dihydropyrimidine dehydrogenase deficiency

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... 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 ...

Classic Bartter syndrome complicated with profound growth hormone deficiency: a case report.

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Adachi, Masanori; Tajima, Toshihiro; Muroya, Koji; Asakura, Yumi

2013-12-30

Classic Bartter syndrome is a salt-wasting tubulopathy caused by mutations in the CLCNKB (chloride channel Kb) gene. Although growth hormone deficiency has been suggested as a cause for persistent growth failure in patients with classic Bartter syndrome, in our opinion the diagnoses of growth hormone deficiency has been unconvincing in some reports. Moreover, Gitelman syndrome seems to have been confused with Bartter syndrome in some cases in the literature. In the present work, we describe a new case with CLCNKB gene mutations and review the reported cases of classic Bartter syndrome associated with growth hormone deficiency. Our patient was a Japanese boy diagnosed as having classic Bartter syndrome at eight months of age. The diagnosis of Bartter syndrome was confirmed by CLCNKB gene analysis, which revealed compound heterozygous mutations with deletion of exons 1 to 3 (derived from his mother) and ΔL130 (derived from his father). His medical therapy consisted of potassium (K), sodium chloride, spironolactone, and anti-inflammatory agents; this regime was started at eight months of age. Our patient was very short (131.1cm, -4.9 standard deviation) at 14.3 years and showed profoundly impaired growth hormone responses to pharmacological stimulants: 0.15μg/L to insulin-induced hypoglycemia and 0.39μg/L to arginine. His growth response to growth hormone therapy was excellent. The present case strengthens the association between classic Bartter syndrome and growth hormone deficiency. We propose that growth hormone status should be considered while treating children with classic Bartter syndrome.

Heterotopic ossification (myositis ossificans) in acquired immune deficiency syndrome. Detection by gallium scintigraphy

International Nuclear Information System (INIS)

Drane, W.E.; Tipler, B.M.

1987-01-01

A case of heterotopic ossification (myositis ossificans) secondary to the central nervous system complications of acquired immune deficiency syndrome (AIDS) is reported. Because of the overwhelming suspicion of infection in this patient, this diagnosis was not considered until a gallium scan revealed the typical findings of heterotopic ossification. Because of the increasing utilization of gallium imaging in the AIDS population, every imaging specialist should be aware of this potential disorder

Nutritional deficiency in citrus with symptoms of citrus variegated chlorosis disease

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ME. Silva-Stenico

Full Text Available It is well known that citrus plants that have been infected by Xylella fastidiosa display nutritional deficiencies, probably caused by production of extracellular polymers by the bacteria that block normal nutrient flow through the xylem. The aim of this work was to study the mineral composition of specific foliar areas in different stages of infection in citrus. Thus, the concentrations of macro and micronutrients in leaves of citrus infected by X. fastidiosa were measured. Samples from four infected citrus orchards in the State of São Paulo, Brazil, were respectively collected from Santa Rita do Passa Quatro, Neves Paulista, Gavião Peixoto and Paraíso counties. The presence of X. fastidiosa in leaves was confirmed by polymerase chain reaction (PCR using specific PCR primers. To understand the variation in leaf-nutrient content in citrus plants, we used foliar nutrient values from control (non-symptomatic plants as a reference. Chemometric analysis showed that the deficiency of P and K in symptomatic trees for all orchards and high concentrations of Fe, Mn and Zn were observed in chlorotic areas, although other studies revealed deficiency of zinc in leaves. This is the first report showing that a correlation between chlorotic citrus leaf and higher concentrations of Fe, Mn and Zn are observed when infected and healthy plants were compared.

Association between iron deficiency anemia and blood level in egyptian children

International Nuclear Information System (INIS)

Nassar, E.M.; Moawad, A.T.; Abd Alla, A.M.

2003-01-01

The relationship between iron deficiency and blood lead levels was investigated in a cross-sectional study of 200 children of both sexes, aged 6-12 years with mean of 7.8 +- 2.6 years. They were randomly selected from governmental primary school located near a highly contaminated industrial area. Blood samples were collected for measuring blood lead levels, serum iron serum ferritin, hemoglobin, mean corpuscular volume (MCV) and total iron binding capacity (TIBC) and other hematological indices. According to iron status, children were classified into non-anemic healthy controls(n=37),iron depleted children(n=58)and children with iron deficiency anemia (n=105).Iron deficiency is defined when MCV 10 / dl were significantly lower than those for children with blood lead levels < 10 /dl. Comparison of blood lead concentrations between boys and girls revealed highly significant increase in blood lead level in boys than girls. A strong negative correlation was detected between blood lead levels and serum iron in all subjects. However, such correlation vanished between blood lead concentration and serum ferritin,so, it could be concluded from the present study that the blood lead levels were changed according to changes in iron status. Improving iron status, along with reducing exposure to environmental contamination with lead, may help in reducing blood lead levels among most children especially those living in contaminated environment

LACTASE DEFICIENCY IN BABIES AND INFANTS

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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.

The ambiguity of ethnicity as risk factor of vitamin D deficiency--a case study of Danish vitamin D policy documents

DEFF Research Database (Denmark)

Mygind, Anna; Traulsen, Janine Morgall; Nørgaard, Lotte Stig

2011-01-01

of interpretative flexibility regarding how ethnic minorities are constructed as a risk group for vitamin D deficiency. The ten documents analysed revealed eight different constructions of the ethnic minorities groups at risk. A low degree of interpretative flexibility was found regarding the importance of skin...... colour and skin covering. Major disagreements were found regarding the importance attributed to the Islamic religion, other traditions, immigration, gender and age, and use of an evolutionary explanation for the increased risk. CONCLUSIONS: Ethnic minorities at risk of vitamin D deficiency......OBJECTIVES: To explore how ethnic minorities at risk of vitamin D deficiency are constructed in Danish policy documents (current as of April 2009), regarding vitamin D supplementation. METHODS: Ten policy documents were analysed through content analysis, focusing on definitions and explanations...

Visual loss and optic nerve head swelling in thiamine deficiency without prolonged dietary deficiency

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Gratton SM

2014-05-01

Full Text Available Sean M Gratton, Byron L LamBascom Palmer Eye Institute, University of Miami, Miller School of Medicine, Miami, FL, USAAbstract: Visual loss due to optic neuropathy is a rare manifestation of thiamine deficiency. We report a case of a 39-year-old woman with a body mass index (BMI of 29 kg/m2 who developed visual loss and bilateral optic nerve head swelling after a short, self-limited gastrointestinal illness. She was disoriented and inattentive and had absent ankle jerk reflexes, diminished sensation in both legs below the knees, and marked truncal ataxia. Magnetic resonance imaging (MRI showed increased T2-signal in the medial thalami and mammillary bodies. The serum thiamine level was 8 nmol/L (normal 8–30. The diagnosis of thiamine deficiency was made, and the patient’s vision and neurologic symptoms improved significantly with intramuscular thiamine treatment. Thiamine deficiency can occur in the absence of an obvious predisposing factor such as alcoholism or low body weight. The clinician must be aware of the factors that govern vitamin availability and maintain a high index of suspicion to make the diagnosis in such cases.Keywords: optic neuropathy, nutritional deficiency

Genetics Home Reference: iron-refractory iron deficiency anemia

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... 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 ...

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.

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 ...

Immunoglobulin class-switch recombination deficiencies.

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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.

Genetics Home Reference: 21-hydroxylase deficiency

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... 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 ...

Genetics Home Reference: ataxia with vitamin E deficiency

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... 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 ...

A case of pyruvate dehydrogenase deficiency with low density areas in white matter noticed by CT scan

International Nuclear Information System (INIS)

Kimura, Akiko; Kyoya, Seizo; Matsushima, Akihiro; Irimichi, Hideki; Koike, Yoshiko.

1985-01-01

The patient was a 4-month-old boy, the first child of healthy, non-consanguineous patient. He was mildly asphyxiated at birth and developed severe convulsions at two days of age. At 4 months of age, he was referred to us because of infantile spasms and motor retardation. The EEG showed hypsarhythmia, ACTH and anticonvulsants were started, but his seizures were not controlled completely. At 8 months of age, the CT scan demonstrated a cerebral atrophy with enlarged ventricles and a diffuse low density of cerebral white matter, and lactic acidosis was first noticed. The glucose, glucagon, fructose, and alanine tolerance tests revealed almost normal responses in blood glucose levels and elevation of lactate levels above the initial value. Enzyme studies revealed a severe deficiency of pyruvate dehydrogenase complex and pyruvate dehydrogenase (E 1 ), and a normal activity of pyruvate carboxylase in liver obtained by biopsy. In biopsied muscle, mitochondria appeared normal. Treatment with thiamine, lipoic acid and anticonvulsants was not effective. The clinical picture of PDC deficiency has been correlated with the amount of the residual activity, and this case confirmed to the ''severe'' category. Several pathologic entities may be associated with PDHC deficiency, and CT findings in our case demonstrated the demyelinating condition. The precise relationship between the defect and the pathogenesis remains to be elucidated. (author)

MSH3-deficiency initiates EMAST without oncogenic transformation of human colon epithelial cells.

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Christoph Campregher

Full Text Available BACKGROUND/AIM: Elevated microsatellite instability at selected tetranucleotide repeats (EMAST is a genetic signature in certain cases of sporadic colorectal cancer and has been linked to MSH3-deficiency. It is currently controversial whether EMAST is associated with oncogenic properties in humans, specifically as cancer development in Msh3-deficient mice is not enhanced. However, a mutator phenotype is different between species as the genetic positions of repetitive sequences are not conserved. Here we studied the molecular effects of human MSH3-deficiency. METHODS: HCT116 and HCT116+chr3 (both MSH3-deficient and primary human colon epithelial cells (HCEC, MSH3-wildtype were stably transfected with an EGFP-based reporter plasmid for the detection of frameshift mutations within an [AAAG]17 repeat. MSH3 was silenced by shRNA and changes in protein expression were analyzed by shotgun proteomics. Colony forming assay was used to determine oncogenic transformation and double strand breaks (DSBs were assessed by Comet assay. RESULTS: Despite differential MLH1 expression, both HCT116 and HCT116+chr3 cells displayed comparable high mutation rates (about 4×10(-4 at [AAAG]17 repeats. Silencing of MSH3 in HCECs leads to a remarkable increased frameshift mutations in [AAAG]17 repeats whereas [CA]13 repeats were less affected. Upon MSH3-silencing, significant changes in the expression of 202 proteins were detected. Pathway analysis revealed overexpression of proteins involved in double strand break repair (MRE11 and RAD50, apoptosis, L1 recycling, and repression of proteins involved in metabolism, tRNA aminoacylation, and gene expression. MSH3-silencing did not induce oncogenic transformation and DSBs increased 2-fold. CONCLUSIONS: MSH3-deficiency in human colon epithelial cells results in EMAST, formation of DSBs and significant changes of the proteome but lacks oncogenic transformation. Thus, MSH3-deficiency alone is unlikely to drive human colon

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.

Zinc Deficiency in Latin America and the Caribbean.

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Cediel, Gustavo; Olivares, Manuel; Brito, Alex; Cori, Héctor; López de Romaña, Daniel

2015-06-01

Zinc deficiency affects multiple vital functions in the life cycle, especially growth. Limited information is available on the magnitude of zinc deficiency in Latin America and the Caribbean. To examine the latest available information on both the prevalence of zinc deficiency and the risk of zinc deficiency in Latin America and the Caribbean. The prevalence of zinc deficiency was identified through a systematic review looking for the latest available data on serum zinc concentrations from surveys or studies with national representativeness conducted in Latin America and the Caribbean. The risk of zinc deficiency in Latin America and the Caribbean was estimated based on dietary zinc inadequacy (according to the 2011 National Food Balance Sheets) and stunting in children under 5 years of age. Only four countries had available national biochemical data. Mexican, Colombian, Ecuadorian, and Guatemalan children under 6 years of age and women 12 to 49 years of age had a high prevalence of zinc deficiency (19.1% to 56.3%). The countries with the highest risk of zinc deficiency (estimated prevalence of inadequate zinc intake > 25% plus prevalence of stunting > 20%) were Belize, Bolivia, El Salvador, Guatemala, Haiti, Honduras, Nicaragua, and Saint Vincent and the Grenadines. Zinc dietary inadequacy was directly correlated with stunting (r = 0.64, p zinc deficiency in children under 6 years of age and women 12 to 49 years of age. High rates of both estimated zinc dietary inadequacy and stunting were also reported in most Latin America and Caribbean countries.

Protein profile of Beta vulgaris leaf apoplastic fluid and changes induced by Fe deficiency and Fe resupply

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Laura eCeballos-Laita

2015-03-01

Full Text Available The fluid collected by direct leaf centrifugation has been used to study the proteome of the sugar beet apoplastic fluid as well as the changes induced by Fe deficiency and Fe resupply to Fe-deficient plants in the protein profile. Plants were grown in Fe-sufficient and Fe-deficient conditions, and Fe resupply was carried out with 45 μM Fe(III-EDTA for 24 h. Protein extracts of leaf apoplastic fluid were analyzed by two-dimensional isoelectric focusing-SDS-PAGE electrophoresis. Gel image analysis revealed 203 consistent spots, and proteins in 81% of them (164 were identified by nLC-MS/MS using a custom made reference repository of beet protein sequences. When redundant UniProt entries were deleted, a non-redundant leaf apoplastic proteome consisting of 109 proteins was obtained. TargetP and SecretomeP algorithms predicted that 63% of them were secretory proteins. Functional classification of the non-redundant proteins indicated that stress and defense, protein metabolism, cell wall and C metabolism accounted for approximately 75% of the identified proteome. The effects of Fe-deficiency on the leaf apoplast proteome were limited, with only five spots (2.5% changing in relative abundance, thus suggesting that protein homeostasis in the leaf apoplast fluid is well maintained upon Fe shortage. The identification of three chitinase isoforms among proteins increasing in relative abundance with Fe-deficiency suggests that one of the few effects of Fe deficiency in the leaf apoplast proteome includes cell wall modifications. Iron resupply to Fe deficient plants changed the relative abundance of 16 spots when compared to either Fe-sufficient or Fe-deficient samples. Proteins identified in these spots can be broadly classified as those responding to Fe-resupply, which included defense and cell wall related proteins, and non-responsive, which are mainly protein metabolism related proteins and whose changes in relative abundance followed the same trend as

Deficiência de ferro no feto e no recém-nascido Iron deficiency in the fetus and newborn

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Maria Renata T. Chopard

2010-06-01

Full Text Available A principal causa de anemia no feto é a doença hemolítica do recém-nascido (RN. As gestantes anêmicas na sua forma moderada não acarretam baixos estoques de ferro no concepto, porém podem evoluir para o trabalho de parto prematuro e RN com baixo peso ao nascer. O ferro é transportado para o feto por via transplacentária, principalmente durante o terceiro trimestre de gestação. A deficiência de ferro não ocorre no período neonatal, porém os prematuros e ou RN com baixo peso constituem o principal grupo de risco para desenvolver a deficiência de ferro. Nos RN nascidos a termo podemos observar uma deficiência de ferro naqueles que sofreram ressecção cirúrgica do duodeno devido à malformação congênita. A fim de evitarmos a deficiência de ferro neste grupo de risco, indica-se a suplementação de ferro a partir dos 30 dias de vida. A via de administração preferencial é a enteral, apesar de sabermos que no prematuro ocorre uma deficiência do controle da absorção do ferro. O complexo de ferro polimaltosado e o ferro aminoquelado são os de escolha para a profilaxia da deficiência de ferro em prematuros. A via endovenosa é segura e não acarreta piora das lesões causadas pela ação oxidativa do ferro em prematuros.The main cause of anemia in the fetus is hemolytic disease. Mildly anemic pregnant women may evolve with premature labor and have low birth weight babies, but the baby's iron status is not influenced by the mother's iron deficiency. Iron transportation through the placenta occurs in the third trimester of gestation and premature labor results in reduced iron stores. Iron deficiency anemia does not occur during the neonatal period, but premature and low birth weight babies are at risk of developing iron deficiency. In full-term babies iron deficiency can occur due to intestinal malformation that leads to duodenal resection. To avoid iron deficiency in at-risk babies, iron supplementation is recommended from

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...

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...

Restoration of adenosine deaminase-deficient human thymocyte development in vitro by inhibition of deoxynucleoside kinases.

Science.gov (United States)

Joachims, Michelle L; Marble, Patrick A; Laurent, Aletha B; Pastuszko, Peter; Paliotta, Marco; Blackburn, Michael R; Thompson, Linda F

2008-12-01

Mutations in the gene encoding adenosine deaminase (ADA), a purine salvage enzyme, lead to immunodeficiency in humans. Although ADA deficiency has been analyzed in cell culture and murine models, information is lacking concerning its impact on the development of human thymocytes. We have used chimeric human/mouse fetal thymic organ culture to study ADA-deficient human thymocyte development in an "in vivo-like" environment where toxic metabolites accumulate in situ. Inhibition of ADA during human thymocyte development resulted in a severe reduction in cellular expansion as well as impaired differentiation, largely affecting mature thymocyte populations. Thymocyte differentiation was not blocked at a discrete stage; rather, the paucity of mature thymocytes was due to the induction of apoptosis as evidenced by activation of caspases and was accompanied by the accumulation of intracellular dATP. Inhibition of adenosine kinase and deoxycytidine kinase prevented the accumulation of dATP and restored thymocyte differentiation and proliferation. Our work reveals that multiple deoxynucleoside kinases are involved in the phosphorylation of deoxyadenosine when ADA is absent, and suggests an alternate therapeutic strategy for treatment of ADA-deficient patients.

Crif1 Deficiency Reduces Adipose OXPHOS Capacity and Triggers Inflammation and Insulin Resistance in Mice

Science.gov (United States)

Ryu, Min Jeong; Kim, Soung Jung; Kim, Yong Kyung; Choi, Min Jeong; Tadi, Surendar; Lee, Min Hee; Lee, Seong Eun; Chung, Hyo Kyun; Jung, Saet Byel; Kim, Hyun-Jin; Jo, Young Suk; Kim, Koon Soon; Lee, Sang-Hee; Kim, Jin Man; Kweon, Gi Ryang; Park, Ki Cheol; Lee, Jung Uee; Kong, Young Yun; Lee, Chul-Ho; Chung, Jongkyeong; Shong, Minho

2013-01-01

Impaired mitochondrial oxidative phosphorylation (OXPHOS) has been proposed as an etiological mechanism underlying insulin resistance. However, the initiating organ of OXPHOS dysfunction during the development of systemic insulin resistance has yet to be identified. To determine whether adipose OXPHOS deficiency plays an etiological role in systemic insulin resistance, the metabolic phenotype of mice with OXPHOS–deficient adipose tissue was examined. Crif1 is a protein required for the intramitochondrial production of mtDNA–encoded OXPHOS subunits; therefore, Crif1 haploinsufficient deficiency in mice results in a mild, but specific, failure of OXPHOS capacity in vivo. Although adipose-specific Crif1-haploinsufficient mice showed normal growth and development, they became insulin-resistant. Crif1-silenced adipocytes showed higher expression of chemokines, the expression of which is dependent upon stress kinases and antioxidant. Accordingly, examination of adipose tissue from Crif1-haploinsufficient mice revealed increased secretion of MCP1 and TNFα, as well as marked infiltration by macrophages. These findings indicate that the OXPHOS status of adipose tissue determines its metabolic and inflammatory responses, and may cause systemic inflammation and insulin resistance. PMID:23516375

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...

Iron-Deficiency Anemia

Medline Plus

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 ...

De novo frameshift mutation in fibroblast growth factor 8 in a male patient with gonadotropin deficiency.

Science.gov (United States)

Suzuki, Erina; Yatsuga, Shuichi; Igarashi, Maki; Miyado, Mami; Nakabayashi, Kazuhiko; Hayashi, Keiko; Hata, Kenichirou; Umezawa, Akihiro; Yamada, Gen; Ogata, Tsutomu; Fukami, Maki

2014-01-01

Missense, nonsense, and splice mutations in the Fibroblast Growth Factor 8(FGF8) have recently been identified in patients with hypothalamo-pituitary dysfunction and craniofacial anomalies. Here, we report a male patient with a frameshift mutation in FGF8. The patient exhibited micropenis, craniofacial anomalies, and ventricular septal defect at birth. Clinical evaluation at 16 years and 8 months of age revealed delayed puberty, hyposmia, borderline mental retardation, and mild hearing difficulty. Endocrine findings included gonadotropin deficiency and primary hypothyroidism. Molecular analysis identified a de novo heterozygous p.S192fsX204 mutation in the last exon of FGF8. RT-PCR analysis of normal human tissues detected FGF8 expression in the genital skin, and whole-mount in situ hybridization analysis of mouse embryos revealed Fgf8 expression in the anlage of the penis. The results indicate that frameshift mutations in FGF8 account for a part of the etiology of hypothalamo-pituitary dysfunction. Micropenis in patients with FGF8 abnormalities appears to be caused by gonadotropin deficiency and defective outgrowth of the anlage of the penis.

UTV Expansion Pack: Special-Purpose Rank-Revealing Algorithms

DEFF Research Database (Denmark)

Fierro, Ricardo D.; Hansen, Per Christian

2005-01-01

This collection of Matlab 7.0 software supplements and complements the package UTV Tools from 1999, and includes implementations of special-purpose rank-revealing algorithms developed since the publication of the original package. We provide algorithms for computing and modifying symmetric rank-r...... values of a sparse or structured matrix. These new algorithms have applications in signal processing, optimization and LSI information retrieval.......This collection of Matlab 7.0 software supplements and complements the package UTV Tools from 1999, and includes implementations of special-purpose rank-revealing algorithms developed since the publication of the original package. We provide algorithms for computing and modifying symmetric rank......-revealing VSV decompositions, we expand the algorithms for the ULLV decomposition of a matrix pair to handle interference-type problems with a rank-deficient covariance matrix, and we provide a robust and reliable Lanczos algorithm which - despite its simplicity - is able to capture all the dominant singular...

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

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

Veganism as a cause of iodine deficient hypothyroidism.

Science.gov (United States)

Yeliosof, Olga; Silverman, Lawrence A

2018-01-26

Iodine deficiency is the most common cause of acquired hypothyroidism worldwide. Although uncommon in the Western world, the incidence of iodine deficiency may be rising due to the increased use of restrictive diets. We present a 23-month-old boy diagnosed with iodine deficiency hypothyroidism, induced by a vegan diet. This case highlights the risk for iodine deficiency in children on a vegan diet after discontinuation of breast/formula feeding that could lead to acquired hypothyroidism.

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.

Clinical, physiological and pathological characterisation of the sensory predominant peripheral neuropathy in copper deficiency.

Science.gov (United States)

Taylor, Sean W; Laughlin, Ruple S; Kumar, Neeraj; Goodman, Brent; Klein, Christopher J; Dyck, Peter J; Dyck, P James B

2017-10-01

Myelopathy is considered the most common neurological complication of copper deficiency. Concurrent peripheral neuropathy has been recognised in association with copper deficiency but has not been well characterised. To characterise the clinical, physiological and pathological features of copper-deficient peripheral neuropathy. Patients with simultaneous copper deficiency (peripheral neuropathy seen at the Mayo Clinic from 1985 to 2005 were identified. 34 patients were identified (median age 55 years, range 36-78) including 24 women and 10 men. Myelopathy was found in 21 patients. Median serum copper level was 0.11 μg/mL (range 0-0.58). The most frequent clinical and electrophysiological pattern of neuropathy was a sensory predominant length-dependent peripheral neuropathy (71%). Somatosensory evoked potentials demonstrated central slowing supporting myelopathy (96%). Quantitative sensory testing demonstrated both small and large fibre involvement (100%). Autonomic reflex screens (77%) and thermoregulatory sweat test (67%) confirmed sudomotor dysfunction. 14 cutaneous nerve biopsies revealed loss of myelinated nerve fibres (86%), increased regenerative clusters (50%), increased rates of axonal degeneration (91%) and increased numbers of empty nerve strands (73%). 71% of biopsies demonstrated epineurial perivascular inflammation. An axonal, length-dependent sensory predominant peripheral neuropathy causing sensory ataxia is characteristic of copper deficiency usually co-occurring with myelopathy. Neurophysiological testing confirms involvement of large, greater than small fibres. The pathological findings suggest axonal degeneration and repair. Inflammatory infiltrates are common but are small and of doubtful pathological significance. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Clinicopathological report of retinitis pigmentosa with vitamin E deficiency caused by mutation of the alpha-tocopherol transfer protein gene.

Science.gov (United States)

Pang, J; Kiyosawa, M; Seko, Y; Yokota, T; Harino, S; Suzuki, J

2001-01-01

To discuss the clinicopathological findings in a patient with retinitis pigmentosa (RP) accompanied by a vitamin E deficiency caused by an H101Q mutation in the alpha-tocopherol transfer protein (alpha-TTP) gene. The clinical course of this patient was followed by conventional ophthalmological examinations over a 3-year period. After the patient died from pancreatic cancer, the eyes were obtained, and examined by light and electron microscopy. The patient complained of night blindness subsequent to adult-onset ataxia, although the ataxia was very mild. His visual acuity was 0.6 OU, and ophthalmoscopy revealed RP sine pigmento. Ring scotomas were detected, and the electroretinography, electro-oculography, and dark-adaptation were altered. Fluorescein angiography showed granular hyperfluorescence around the macula. No progression of the visual and neurological symptoms was observed during the 10 years he was taking oral vitamin E. Histopathological examination revealed the loss of the outer and inner segments of the photoreceptors in the area corresponding to the ring scotoma, as well as a disorganization and shortening of the outer segments in the peripheral retina. We conclude that the clinical and pathological findings in the eyes of this patient having RP with vitamin E deficiency caused by an H101Q mutation are similar to those of common autosomal recessive RP. However, special attention is required in making a diagnosis of RP with vitamin E deficiency because RP with vitamin E deficiency is medically treatable. The mild Friedreich-type ataxia accompanying the RP may be helpful in identifying this disease.

Is vitamin D deficiency a public health concern for low middle income countries? A systematic literature review.

Science.gov (United States)

Cashman, Kevin D; Sheehy, Tony; O'Neill, Colette M

2018-01-17

Vitamin D deficiency has been receiving increasing attention as a potential public health concern in low and lower-middle income countries (LMICs), of which there are currently 83. We aimed to conduct a comprehensive systematic literature review (SLR) of available data on vitamin D status and prevalence of vitamin D deficiency in all 83 LMICs. We followed the general methodology for SLRs in the area of serum 25-hydroxyvitamin D. Highest priority was placed on identifying relevant population-based studies, followed by cross-sectional studies, and to a lesser extent case-control studies. We adopted the public health convention that a prevalence of vitamin D deficiency (serum 25-hydroxyvitamin D  20% in the entire population and/or at-risk population subgroups (infants, children, women of child-bearing age, pregnancy) constitutes a public health issue that may warrant intervention. Our SLR revealed that of the 83 LMICs, 65% (n = 54 countries) had no published studies with vitamin D data suitable for inclusion. Using data from the remaining third, a number of LMICs had evidence of excess burden of vitamin D deficiency in one or more population subgroup(s) using the above convention (Afghanistan, Pakistan, India, Tunisia and Mongolia) as well as possibly other LMICs, albeit with much more limited data. Several LMICs had no evidence of excess burden. Vitamin D deficiency is a public health issue in some, but certainly not all, LMICs. There is a clear need for targeting public health strategies for prevention of vitamin D deficiency in those LMICs with excess burden.

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.

Iron-Deficiency Anemia

Medline Plus

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 ...

Iron-Deficiency Anemia

Medline Plus

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 ...

Association of glucose-6-phosphate dehydrogenase deficiency and X-linked chronic granulomatous disease in a child with anemia and recurrent infections

OpenAIRE

Agudelo-Florez, P.; Costa-Carvalho, Beatriz Tavares [UNIFESP; Lopez, J. A.; Redher, J.; Newburger, P. E.; Alla-Saad, S. T.; Condino-Neto, A.

2004-01-01

Patients with severe leukocyte G6PD deficiency may present with impairment of NADPH oxidase activity and a history of recurrent infections, mimicking the phenotype of chronic granulomatous disease. We report herein a child with recurrent infections who initially received the diagnosis of G6PD deficiency. His erythrocyte G6PD activity was reduced: 1.8 U/g Hb (normal: 12.1 +/- 2.1 U/g Hb). Further studies revealed that G6PD activity in neutrophils, mononuclear leukocytes, and Epstein-Barr virus...

Facile Aluminum Reduction Synthesis of Blue TiO2 with Oxygen Deficiency for Lithium-Ion Batteries.

Science.gov (United States)

Zheng, Jing; Ji, Guangbin; Zhang, Peng; Cao, Xingzhong; Wang, Baoyi; Yu, Linghui; Xu, Zhichuan J

2015-12-07

An ultrafacile aluminum reduction method is reported herein for the preparation of blue TiO2 nanoparticles (donated as Al-TiO2 , anatase phase) with abundant oxygen deficiency for lithium-ion batteries. Under aluminum reduction, the morphology of the TiO2 nanosheets changes from well-defined rectangular into uniform round or oval nanoparticles and the particle size also decreases from 60 to 31 nm, which can aggressively accelerate the lithium-ion diffusion. Electron paramagnetic resonance (EPR) and positron annihilation lifetime spectroscopy (PALS) results reveal that plentiful oxygen deficiencies relative to the Ti(3+) species were generated in blue Al-TiO2 ; this effectively enhances the electron conductivity of the TiO2 . X-ray photoelectron spectrometry (XPS) analysis indicates that a small peak is observed for the Al-O bond, which probably plays a very important role in the stabilization of the oxygen deficiencies/Ti(3+) species. As a result, the blue Al-TiO2 possesses significantly higher capacity, better rate performance, and a longer cycle life than the white pure TiO2 . Such improvements can be attributed to the decreased particle size, as well as the existence of the oxygen deficiencies/Ti(3+) species. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Biochemical Assessment of Coenzyme Q10 Deficiency

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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.

MutLα Heterodimers Modify the Molecular Phenotype of Friedreich Ataxia

Science.gov (United States)

Ezzatizadeh, Vahid; Sandi, Chiranjeevi; Sandi, Madhavi; Anjomani-Virmouni, Sara; Al-Mahdawi, Sahar; Pook, Mark A.

2014-01-01

Background Friedreich ataxia (FRDA), the most common autosomal recessive ataxia disorder, is caused by a dynamic GAA repeat expansion mutation within intron 1 of FXN gene, resulting in down-regulation of frataxin expression. Studies of cell and mouse models have revealed a role for the mismatch repair (MMR) MutS-heterodimer complexes and the PMS2 component of the MutLα complex in the dynamics of intergenerational and somatic GAA repeat expansions: MSH2, MSH3 and MSH6 promote GAA repeat expansions, while PMS2 inhibits GAA repeat expansions. Methodology/Principal Findings To determine the potential role of the other component of the MutLα complex, MLH1, in GAA repeat instability in FRDA, we have analyzed intergenerational and somatic GAA repeat expansions from FXN transgenic mice that have been crossed with Mlh1 deficient mice. We find that loss of Mlh1 activity reduces both intergenerational and somatic GAA repeat expansions. However, we also find that loss of either Mlh1 or Pms2 reduces FXN transcription, suggesting different mechanisms of action for Mlh1 and Pms2 on GAA repeat expansion dynamics and regulation of FXN transcription. Conclusions/Significance Both MutLα components, PMS2 and MLH1, have now been shown to modify the molecular phenotype of FRDA. We propose that upregulation of MLH1 or PMS2 could be potential FRDA therapeutic approaches to increase FXN transcription. PMID:24971578

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.

Iron-Deficiency Anemia

Medline Plus

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 ...

MHC class II expression through a hitherto unknown pathway supports T helper cell-dependent immune responses: implications for MHC class II deficiency.

Science.gov (United States)

Buch, Thorsten; Polic, Bojan; Clausen, Björn E; Weiss, Susanne; Akilli-Ozturk, Ozlem; Chang, Cheong-Hee; Flavell, Richard; Schulz, Ansgar; Jonjic, Stipan; Waisman, Ari; Förster, Irmgard

2006-02-15

MHC class II (MHCII) deficiency or bare lymphocyte syndrome (BLS) is a severe immunodeficiency characterized by deficient T helper (Th)-cell-dependent immunity. The disease is caused by defects of the MHCII promoter complex resulting in low or absent MHCII expression. We demonstrate in a murine model of MHCII deficiency (RFX5- or CIITA-deficient mice) that residual MHCII expression by professional antigen-presenting cells (APCs) is sufficient to support activation of adoptively transferred Th cells. Furthermore, upon transplantation of WT thymic epithelium, we observed development of endogenous Th cells with restoration of Th-cell-dependent antibody responses and immunity to cytomegalovirus infection, thus opening the possibility of an alternative treatment regimen for BLS. Residual MHCII expression was further induced by the presence of Th cells and also other stimuli. Analysis of CIITA/RFX5 double-deficient animals revealed that this inducible MHCII expression is genetically independent of the known promoter complex and thus constitutes an alternative MHCII expression pathway. In these experiments, we also detected a novel repressive function of the RFX complex in the absence of CIITA.

Isolated Cortisol Deficiency: A Rare Cause of Neonatal Cholestasis

Science.gov (United States)

Al-Hussaini, Abdulrahman; Almutairi, Awatif; Mursi, Alaaddin; Alghofely, Mohammed; Asery, Ali

2012-01-01

For decades, congenital panhypopituitarism has been recognized to cause infantile cholestasis. However, the identity of the hormone whose deficiency causes such derangement of the liver is not clear. Here, we report four cases of isolated severe cortisol deficiency presenting with neonatal cholestasis and hypoglycemia, of whom two had familial primary glucocorticoid deficiency and the other two had isolated adrenocorticotropin deficiency. The resolution of cholestasis by hydrocortisone replacement therapy suggests a causal relationship between cortisol deficiency and the development of neonatal cholestasis. In conclusion, the presentation of a young infant with cholestasis and hypoglycemia should alert pediatricians to the possibility of cortisol deficiency and prompt investigation of adrenal function should be undertaken. PMID:23006463

Screening for iron deficiency and iron deficiency anaemia in pregnancy: a structured review and gap analysis against UK national screening criteria.

Science.gov (United States)

Rukuni, Ruramayi; Knight, Marian; Murphy, Michael F; Roberts, David; Stanworth, Simon J

2015-10-20

Iron deficiency anaemia is a common problem in pregnancy despite national recommendations and guidelines for treatment. The aim of this study was to appraise the evidence against the UK National Screening Committee (UKNSC) criteria as to whether a national screening programme could reduce the prevalence of iron deficiency anaemia and/or iron deficiency in pregnancy and improve maternal and fetal outcomes. Search strategies were developed for the Cochrane library, Medline and Embase to identify evidence relevant to UK National Screening Committee (UKNSC) appraisal criteria which cover the natural history of iron deficiency and iron deficiency anaemia, the tests for screening, clinical management and evidence of cost effectiveness. Many studies evaluated haematological outcomes of anaemia, but few analysed clinical consequences. Haemoglobin and ferritin appeared the most suitable screening tests, although future options may follow recent advances in understanding iron homeostasis. The clinical consequences of iron deficiency without anaemia are unknown. Oral and intravenous iron are effective in improving haemoglobin and iron parameters. There have been no trials or economic evaluations of a national screening programme for iron deficiency anaemia in pregnancy. Iron deficiency in pregnancy remains an important problem although effective tests and treatment exist. A national screening programme could be of value for early detection and intervention. However, high quality studies are required to confirm whether this would reduce maternal and infant morbidity and be cost effective.

Bioenergetics of the calf muscle in Friedreich ataxia patients measured by 31P-MRS before and after treatment with recombinant human erythropoietin.

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Wolfgang Nachbauer

Full Text Available Friedreich ataxia (FRDA is caused by a GAA repeat expansion in the FXN gene leading to reduced expression of the mitochondrial protein frataxin. Recombinant human erythropoietin (rhuEPO is suggested to increase frataxin levels, alter mitochondrial function and improve clinical scores in FRDA patients. Aim of the present pilot study was to investigate mitochondrial metabolism of skeletal muscle tissue in FRDA patients and examine effects of rhuEPO administration by phosphorus 31 magnetic resonance spectroscopy (31P MRS. Seven genetically confirmed FRDA patients underwent 31P MRS of the calf muscles using a rest-exercise-recovery protocol before and after receiving 3000 IU of rhuEPO for eight weeks. FRDA patients showed more rapid phosphocreatine (PCr depletion and increased accumulation of inorganic phosphate (Pi during incremental exercise as compared to controls. After maximal exhaustive exercise prolonged regeneration of PCR and slowed decline in Pi can be seen in FRDA. PCr regeneration as hallmark of mitochondrial ATP production revealed correlation to activity of complex II/III of the respiratory chain and to demographic values. PCr and Pi kinetics were not influenced by rhuEPO administration. Our results confirm mitochondrial dysfunction and exercise intolerance due to impaired oxidative phosphorylation in skeletal muscle tissue of FRDA patients. MRS did not show improved mitochondrial bioenergetics after eight weeks of rhuEPO exposition in skeletal muscle tissue of FRDA patients.EU Clinical Trials Register2008-000040-13.

Clinical implications of vitamin D deficiency

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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.

Deficiência de ferro na criança Iron deficiency in infants and children

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Josefina A. P. Braga

2010-06-01

Full Text Available Estima-se que dois bilhões de indivíduos sejam anêmicos e que a deficiência de ferro ocorra em cerca de quatro bilhões de indivíduos, afetando a população de países desenvolvidos e, com mais intensidade, a dos países em desenvolvimento. No Brasil, estudos apontam elevada prevalência de anemia ferropriva em crianças dependendo da região e da faixa etária. A velocidade de crescimento aumentada, determinando maior necessidade de ferro, aliada a dieta inadequada em ferro e ao desmame precoce, contribuem para a elevada prevalência de anemia, principalmente nos dois primeiros anos de vida. Outros fatores de risco são apontados, como a prematuridade, o baixo peso ao nascer, a ligadura precoce do cordão umbilical e o abandono do aleitamento materno exclusivo. O impacto da deficiência de ferro no crescimento permanece controverso, uma vez que inúmeras outras variáveis poderiam contribuir para melhora ou piora do estado nutricional. Alterações no desenvolvimento psicomotor e neurocognitivo, nos lactentes deficientes com ferro, têm sido relatadas em diversos estudos, sendo controversa a recuperação após o tratamento. Há trabalhos que demonstram queda no rendimento intelectual e nas aquisições cognitivas também no período escolar e adolescência, com reversão após a terapia marcial. Entre as medidas preventivas, a educação nutricional é a forma ideal; entretanto, frente à elevada prevalência, outras formas de prevenção devem ser também utilizadas, como a suplementação com ferro e a fortificação de alimentos com ferro.Iron deficiency anemia afflicts an estimated two billion people and iron deficiency approximately 4 billion people in developed countries and is even more common in developing countries. In Brazil, depending on the region and age, studies point to high prevalences of iron-deficiency anemia in children. The high growth speed, which requires a greater amount of iron, connected with an inadequate iron

ATM-deficiency increases genomic instability and metastatic potential in a mouse model of pancreatic cancer.

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Drosos, Yiannis; Escobar, David; Chiang, Ming-Yi; Roys, Kathryn; Valentine, Virginia; Valentine, Marc B; Rehg, Jerold E; Sahai, Vaibhav; Begley, Lesa A; Ye, Jianming; Paul, Leena; McKinnon, Peter J; Sosa-Pineda, Beatriz

2017-09-11

Germline mutations in ATM (encoding the DNA-damage signaling kinase, ataxia-telangiectasia-mutated) increase Familial Pancreatic Cancer (FPC) susceptibility, and ATM somatic mutations have been identified in resected human pancreatic tumors. Here we investigated how Atm contributes to pancreatic cancer by deleting this gene in a murine model of the disease expressing oncogenic Kras (Kras G12D ). We show that partial or total ATM deficiency cooperates with Kras G12D to promote highly metastatic pancreatic cancer. We also reveal that ATM is activated in pancreatic precancerous lesions in the context of DNA damage and cell proliferation, and demonstrate that ATM deficiency leads to persistent DNA damage in both precancerous lesions and primary tumors. Using low passage cultures from primary tumors and liver metastases we show that ATM loss accelerates Kras-induced carcinogenesis without conferring a specific phenotype to pancreatic tumors or changing the status of the tumor suppressors p53, p16 Ink4a and p19 Arf . However, ATM deficiency markedly increases the proportion of chromosomal alterations in pancreatic primary tumors and liver metastases. More importantly, ATM deficiency also renders murine pancreatic tumors highly sensitive to radiation. These and other findings in our study conclusively establish that ATM activity poses a major barrier to oncogenic transformation in the pancreas via maintaining genomic stability.

Telomerase deficiency in bone marrow-derived cells attenuates angiotensin II-induced abdominal aortic aneurysm formation.

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Findeisen, Hannes M; Gizard, Florence; Zhao, Yue; Cohn, Dianne; Heywood, Elizabeth B; Jones, Karrie L; Lovett, David H; Howatt, Deborah A; Daugherty, Alan; Bruemmer, Dennis

2011-02-01

Abdominal aortic aneurysms (AAA) are an age-related vascular disease and an important cause of morbidity and mortality. In this study, we sought to determine whether the catalytic component of telomerase, telomerase reverse transcriptase (TERT), modulates angiotensin (Ang) II-induced AAA formation. Low-density lipoprotein receptor-deficient (LDLr-/-) mice were lethally irradiated and reconstituted with bone marrow-derived cells from TERT-deficient (TERT-/-) mice or littermate wild-type mice. Mice were placed on a diet enriched in cholesterol, and AAA formation was quantified after 4 weeks of Ang II infusion. Repopulation of LDLr-/- mice with TERT-/- bone marrow-derived cells attenuated Ang II-induced AAA formation. TERT-deficient recipient mice revealed modest telomere attrition in circulating leukocytes at the study end point without any overt effect of the donor genotype on white blood cell counts. In mice repopulated with TERT-/- bone marrow, aortic matrix metalloproteinase-2 (MMP-2) activity was reduced, and TERT-/- macrophages exhibited decreased expression and activity of MMP-2 in response to stimulation with Ang II. Finally, we demonstrated in transient transfection studies that TERT overexpression activates the MMP-2 promoter in macrophages. TERT deficiency in bone marrow-derived macrophages attenuates Ang II-induced AAA formation in LDLr-/- mice and decreases MMP-2 expression. These results point to a previously unrecognized role of TERT in the pathogenesis of AAA.

NHE1 deficiency in liver: Implications for non-alcoholic fatty liver disease

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Prasad, Vikram, E-mail: prasadvm@ucmail.uc.edu [Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine (United States); Chirra, Shivani [Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine (United States); Kohli, Rohit [Department of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children’s Hospital, University of Cincinnati, Cincinnati, OH 45267 (United States); Shull, Gary E. [Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine (United States)

2014-07-25

Highlights: • FXR, PGC1α and PPARγ levels are upregulated in NHE1 deficient livers. • NHE1 deficiency downregulates expression of pro-lipogenic genes in liver. • Chronic exposure to high-fat diet upregulates hepatic NHE1 expression. • Loss of NHE1 better preserves hepatic insulin signaling in high-fat diet-fed mice. - Abstract: Non-alcoholic fatty liver disease NAFLD is closely associated with the dysregulation of lipid homeostasis. Diet-induced hepatic steatosis, which can initiate NAFLD progression, has been shown to be dramatically reduced in mice lacking the electroneutral Na{sup +}/H{sup +} exchanger NHE1 (Slc9a1). In this study, we investigated if NHE1 deficiency had effects in liver that could contribute to the apparent protection against aberrant lipid accumulation. RT-PCR and immunoblot analyses of wild-type and NHE1-null livers revealed an expression profile that strongly suggested attenuation of both de novo lipogenesis and hepatic stellate cell activation, which is implicated in liver fibrosis. This included upregulation of the farnesoid X receptor FXR, peroxisome proliferator-activated receptor PPARγ, its co-activator PGC1α, and sestrin 2, an antioxidant protein involved in hepatic metabolic homeostasis. Furthermore, expression levels of the pro-lipogenic liver X receptor LXRα, and acetyl CoA carboxylases 1 and 2 were downregulated. These changes were associated with evidence of reduced cellular stress, which persisted even upon exposure to a high-fat diet, and the better preservation of insulin signaling, as evidenced by protein kinase B/Akt phosphorylation (Ser473). These results indicate that NHE1 deficiency may protect against NAFLD pathogenesis, which is significant given the availability of highly specific NHE1 inhibitors.

NHE1 deficiency in liver: Implications for non-alcoholic fatty liver disease

International Nuclear Information System (INIS)

Prasad, Vikram; Chirra, Shivani; Kohli, Rohit; Shull, Gary E.

2014-01-01

Highlights: • FXR, PGC1α and PPARγ levels are upregulated in NHE1 deficient livers. • NHE1 deficiency downregulates expression of pro-lipogenic genes in liver. • Chronic exposure to high-fat diet upregulates hepatic NHE1 expression. • Loss of NHE1 better preserves hepatic insulin signaling in high-fat diet-fed mice. - Abstract: Non-alcoholic fatty liver disease NAFLD is closely associated with the dysregulation of lipid homeostasis. Diet-induced hepatic steatosis, which can initiate NAFLD progression, has been shown to be dramatically reduced in mice lacking the electroneutral Na + /H + exchanger NHE1 (Slc9a1). In this study, we investigated if NHE1 deficiency had effects in liver that could contribute to the apparent protection against aberrant lipid accumulation. RT-PCR and immunoblot analyses of wild-type and NHE1-null livers revealed an expression profile that strongly suggested attenuation of both de novo lipogenesis and hepatic stellate cell activation, which is implicated in liver fibrosis. This included upregulation of the farnesoid X receptor FXR, peroxisome proliferator-activated receptor PPARγ, its co-activator PGC1α, and sestrin 2, an antioxidant protein involved in hepatic metabolic homeostasis. Furthermore, expression levels of the pro-lipogenic liver X receptor LXRα, and acetyl CoA carboxylases 1 and 2 were downregulated. These changes were associated with evidence of reduced cellular stress, which persisted even upon exposure to a high-fat diet, and the better preservation of insulin signaling, as evidenced by protein kinase B/Akt phosphorylation (Ser473). These results indicate that NHE1 deficiency may protect against NAFLD pathogenesis, which is significant given the availability of highly specific NHE1 inhibitors

Netherton Syndrome in a Neonate with Possible Growth Hormone Deficiency and Transient Hyperaldosteronism

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Chatziioannidis Ilias

2015-01-01

Full Text Available Netherton syndrome, a rare autosomal recessive genetic disorder, is classified as an ichthyosiform syndrome. In this report we present the case of a neonate with erythroderma shortly after birth, accompanied by severe hypernatremia, recurrent infections, transient hyperaldosteronism, and signs of growth hormone (GH deficiency. DNA molecular analysis in the SPINK5 gene revealed heterozygosity in our index patient for 238insG and 2468delA frameshift mutations in exons 4 and 26, respectively, in the maternal allele and 1431-12G>A splice-site mutation in intron 15 in the paternal allele as well as the missense variation E420K in homozygous state. Combination of the identified mutations along with transient hyperaldosteronism and possible GH deficiency have not been described before. Accordingly, the importance of early multidisciplinary approach is highlighted, in order to reach accurate diagnosis, initiate prompt treatment, and ensure survival with fewer disease complications.

Vitamin-A deficiency and its determinants among preschool children: a community based cross-sectional study in Ethiopia.

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Tariku, Amare; Fekadu, Abel; Ferede, Ayanaw Tsega; Mekonnen Abebe, Solomon; Adane, Akilew Awoke

2016-06-24

Vitamin A deficiency is the leading cause of preventable visual impairments in children. It is also an underlying cause for nearly one-fourth of global child mortality associated with measles, diarrhea, and malaria. The limited literature available in Ethiopia shows severe public health significance of vitamin-A deficiency. Hence the aim of the current study was to assess the prevalence and factors determining vitamin-A deficiency among preschool children in Dembia District, northwest Ethiopia. A community-based cross-sectional study was conducted among preschool children of Dembia District from January to February, 2015. A multi-stage sampling, followed by a systematic sampling technique was employed to select study participants. A structured interviewer-administered questionnaire was used to collect data. Using a binary logistic regression model, multivariable analysis was fitted to identify the associated factors of vitamin-A deficiency. The adjusted odds ratio (AOR) with a 95 % confidence interval was computed to assess the strength of the association, and variables with a p value of preschool children were included in the study, giving a response rate of 96.5 %. The overall prevalence of xerophthalmia was 8.6 %. The result of the multivariable analysis revealed that nonattendance at the antenatal care clinic [AOR 2.65,95 % CI (1.39,5.07)], being male [AOR 1.81, 95 % CI (1.01,3.24)], and in the age group of 49-59 months [AOR 3.00, 95 % CI (1.49,6.02)] were significantly associated with vitamin-A deficiency. Vitamin-A deficiency is a severe public health problem in the study area. Further strengthening antenatal care utilization and giving emphasis to preschool children will help to mitigate vitamin-A deficiency in the study area.

Radiochemical studies of neutron deficient actinide isotopes

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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

Dedicator of cytokinesis 8-deficient CD4+ T cells are biased to a TH2 effector fate at the expense of TH1 and TH17 cells.

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Tangye, Stuart G; Pillay, Bethany; Randall, Katrina L; Avery, Danielle T; Phan, Tri Giang; Gray, Paul; Ziegler, John B; Smart, Joanne M; Peake, Jane; Arkwright, Peter D; Hambleton, Sophie; Orange, Jordan; Goodnow, Christopher C; Uzel, Gulbu; Casanova, Jean-Laurent; Lugo Reyes, Saul Oswaldo; Freeman, Alexandra F; Su, Helen C; Ma, Cindy S

2017-03-01

Dedicator of cytokinesis 8 (DOCK8) deficiency is a combined immunodeficiency caused by autosomal recessive loss-of-function mutations in DOCK8. This disorder is characterized by recurrent cutaneous infections, increased serum IgE levels, and severe atopic disease, including food-induced anaphylaxis. However, the contribution of defects in CD4 + T cells to disease pathogenesis in these patients has not been thoroughly investigated. We sought to investigate the phenotype and function of DOCK8-deficient CD4 + T cells to determine (1) intrinsic and extrinsic CD4 + T-cell defects and (2) how defects account for the clinical features of DOCK8 deficiency. We performed in-depth analysis of the CD4 + T-cell compartment of DOCK8-deficient patients. We enumerated subsets of CD4 + T helper cells and assessed cytokine production and transcription factor expression. Finally, we determined the levels of IgE specific for staple foods and house dust mite allergens in DOCK8-deficient patients and healthy control subjects. DOCK8-deficient memory CD4 + T cells were biased toward a T H 2 type, and this was at the expense of T H 1 and T H 17 cells. In vitro polarization of DOCK8-deficient naive CD4 + T cells revealed the T H 2 bias and T H 17 defect to be T-cell intrinsic. Examination of allergen-specific IgE revealed plasma IgE from DOCK8-deficient patients is directed against staple food antigens but not house dust mites. Investigations into the DOCK8-deficient CD4 + T cells provided an explanation for some of the clinical features of this disorder: the T H 2 bias is likely to contribute to atopic disease, whereas defects in T H 1 and T H 17 cells compromise antiviral and antifungal immunity, respectively, explaining the infectious susceptibility of DOCK8-deficient patients. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. All rights reserved.

Sintomas visuais de deficiências nutricionais em pinhão-manso Visual symptoms of nutrient deficiency in physic nut

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Enilson de Barros Silva

2009-04-01

Full Text Available O objetivo deste trabalho foi avaliar o crescimento e caracterizar os sintomas de deficiências de macro e micronutrientes em mudas de pinhão-manso (Jatropha curcas. As mudas foram cultivadas em solução nutritiva completa e, também, em soluções com omissão de N, P, K, Ca, Mg, S, B, Cu, Fe, Mn ou Zn, pelo uso da técnica do elemento faltante. Foram avaliados os sintomas visuais de deficiência de nutrientes e a massa de matéria seca da parte aérea e das raízes, respectivamente aos 90 e 120 dias após a aplicação dos tratamentos. As omissões de macro e micronutrientes provocaram sintomas visuais de deficiência nutricional comuns a outras espécies. As deficiências limitaram a produção de massa de matéria seca na seguinte ordem: Ca>Mg>K>N>P>S, para macronutrientes; e Fe>Cu>Zn>Mn>B, para micronutrientes.The objectives of this work were to evaluate the growth of physic nut (Jatropha curcas and to characterize visual symptoms of macro and micronutrient deficiencies in seedlings. The seedlings were cultivated in nutritive solution containing all required macro and micronutrients and in solutions with omission of N, P, K, Ca, Mg, S, B, Cu, Fe, Mn or Zn, using the missing element technique. Visual deficiency symptoms and seedlings dry weight were evaluated at 90 and 120 days after treatments, respectively. The absences of macro and micronutrients in physic nut caused in nutritional deficiency visual symptoms known to other species. The deficiencies restricted the dry matter production according to the following order: Ca>Mg>K>N>P>S, for macronutrients, and Fe>Cu>Zn>Mn>B, for micronutrients.

Deficient and Null Variants of SERPINA1 Are Proteotoxic in a Caenorhabditis elegans Model of α1-Antitrypsin Deficiency.

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Erin E Cummings

Full Text Available α1-antitrypsin deficiency (ATD predisposes patients to both loss-of-function (emphysema and gain-of-function (liver cirrhosis phenotypes depending on the type of mutation. Although the Z mutation (ATZ is the most prevalent cause of ATD, >120 mutant alleles have been identified. In general, these mutations are classified as deficient (<20% normal plasma levels or null (<1% normal levels alleles. The deficient alleles, like ATZ, misfold in the ER where they accumulate as toxic monomers, oligomers and aggregates. Thus, deficient alleles may predispose to both gain- and loss-of-function phenotypes. Null variants, if translated, typically yield truncated proteins that are efficiently degraded after being transiently retained in the ER. Clinically, null alleles are only associated with the loss-of-function phenotype. We recently developed a C. elegans model of ATD in order to further elucidate the mechanisms of proteotoxicity (gain-of-function phenotype induced by the aggregation-prone deficient allele, ATZ. The goal of this study was to use this C. elegans model to determine whether different types of deficient and null alleles, which differentially affect polymerization and secretion rates, correlated to any extent with proteotoxicity. Animals expressing the deficient alleles, Mmalton, Siiyama and S (ATS, showed overall toxicity comparable to that observed in patients. Interestingly, Siiyama expressing animals had smaller intracellular inclusions than ATZ yet appeared to have a greater negative effect on animal fitness. Surprisingly, the null mutants, although efficiently degraded, showed a relatively mild gain-of-function proteotoxic phenotype. However, since null variant proteins are degraded differently and do not appear to accumulate, their mechanism of proteotoxicity is likely to be different to that of polymerizing, deficient mutants. Taken together, these studies showed that C. elegans is an inexpensive tool to assess the proteotoxicity of

A case of succinic semialdehyde dehydrogenase deficiency with status epilepticus and rapid regression.

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Horino, Asako; Kawawaki, Hisashi; Fukuoka, Masataka; Tsuji, Hitomi; Hattori, Yuka; Inoue, Takeshi; Nukui, Megumi; Kuki, Ichiro; Okazaki, Shin; Tomiwa, Kiyotaka; Hirose, Shinichi

2016-10-01

Clinical phenotypic expression of SSADH deficiency is highly heterogeneous, and some infants may develop refractory secondary generalized seizures. A 9-month-old boy manifested partial seizures, developing severe status epilepticus, and conventional antiepileptic drugs were ineffective. Use of ketamine contributed to the control of status epilepticus, achieving a reduction in frequency of partial seizures, and improving EEG findings without apparent complications. Diffusion-weighted images showed hyperintensities in the bilateral basal ganglia and fornix, and multiple T2 hyperintensity lesions were detected. (123)I-iomazenil (IMZ) SPECT revealed a decrease in binding of (123)I-iomazenil predominantly in the left temporal region by the 18th day of hospitalization. However, repeated IMZ-SPECT on the 46th day of hospitalization demonstrated almost no accumulation across a broad region, sparing the left temporal region. The patient showed rapid regression, refractory myoclonus, and severe progressive brain atrophy. IMZ-SPECT findings demonstrated reduced benzodiazepine receptor binding and its dynamic changes in an SSADH-deficient patient. Considering the down regulation of the GABAA receptor, ketamine should be included in pharmacotherapeutic strategies for treatment of refractory status epilepticus in SSADH-deficient patients. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Deficient Circumferential Growth Is the Primary Determinant of Aortic Obstruction Attributable to Partial Elastin Deficiency.

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Jiao, Yang; Li, Guangxin; Korneva, Arina; Caulk, Alexander W; Qin, Lingfeng; Bersi, Matthew R; Li, Qingle; Li, Wei; Mecham, Robert P; Humphrey, Jay D; Tellides, George

2017-05-01

Williams syndrome is characterized by obstructive aortopathy attributable to heterozygous loss of ELN , the gene encoding elastin. Lesions are thought to result primarily from excessive smooth muscle cell (SMC) proliferation and consequent medial expansion, although an initially smaller caliber and increased stiffness of the aorta may contribute to luminal narrowing. The relative contributions of such abnormalities to the obstructive phenotype had not been defined. We quantified determinants of luminal stenosis in thoracic aortas of Eln -/- mice incompletely rescued by human ELN . Moderate obstruction was largely because of deficient circumferential growth, most prominently of ascending segments, despite increased axial growth. Medial thickening was evident in these smaller diameter elastin-deficient aortas, with medial area similar to that of larger diameter control aortas. There was no difference in cross-sectional SMC number between mutant and wild-type genotypes at multiple stages of postnatal development. Decreased elastin content was associated with medial fibrosis and reduced aortic distensibility because of increased structural stiffness but preserved material stiffness. Elastin-deficient SMCs exhibited greater contractile-to-proliferative phenotypic modulation in vitro than in vivo. We confirmed increased medial collagen without evidence of increased medial area or SMC number in a small ascending aorta with thickened media of a Williams syndrome subject. Deficient circumferential growth is the predominant mechanism for moderate obstructive aortic disease resulting from partial elastin deficiency. Our findings suggest that diverse aortic manifestations in Williams syndrome result from graded elastin content, and SMC hyperplasia causing medial expansion requires additional elastin loss superimposed on ELN haploinsufficiency. © 2017 American Heart Association, Inc.

Effects of betaine supplementation and choline deficiency on folate deficiency-induced hyperhomocysteinemia in rats.

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Liu, Ying; Liu, Yi-qun; Morita, Tatsuya; Sugiyama, Kimio

2012-01-01

The effect of betaine status on folate deficiency-induced hyperhomocysteinemia was investigated to determine whether folate deficiency impairs homocysteine removal not only by the methionine synthase (MS) pathway but also by the betaine-homocysteine S-methyltransferase (BHMT) pathway. For this purpose, we investigated the effect of dietary supplementation with betaine at a high level (1%) in rats fed a folate-deprived 10% casein diet (10C) and 20% casein diet (20C). We also investigated the effect of choline deprivation on folate deficiency-induced hyperhomocysteinemia in rats fed 20C. Supplementation of folate-deprived 10C and 20C with 1% betaine significantly suppressed folate deprivation-induced hyperhomocysteinemia, but the extent of suppression was partial or limited, especially in rats fed 10C, the suppression of plasma homocysteine increment being 48.5% in rats fed 10C and 69.7% in rats fed 20C. Although betaine supplementation greatly increased hepatic betaine concentration and BHMT activity, these increases did not fully explain why the effect of betaine supplementation was partial or limited. Folate deprivation markedly increased the hepatic concentration of N,N-dimethylglycine (DMG), a known inhibitor of BHMT, and there was a significant positive correlation between hepatic DMG concentration and plasma homocysteine concentration, suggesting that folate deficiency increases hepatic DMG concentration and thereby depresses BHMT reaction, leading to interference with the effect of betaine supplementation. Choline deprivation did not increase plasma homocysteine concentration in rats fed 20C, but it markedly enhanced plasma homocysteine concentration when rats were fed folate-deprived 20C. This indicates that choline deprivation reinforced folate deprivation-induced hyperhomocysteinemia. Increased hepatic DMG concentration was also associated with such an effect. These results support the concept that folate deficiency impairs homocysteine metabolism not only

Cobalamin C deficiency in an adolescent with altered mental status and anorexia.

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Rahmandar, Maria H; Bawcom, Amanda; Romano, Mary E; Hamid, Rizwan

2014-12-01

Although cobalamin (cbl) C deficiency is the most common inherited disorder of vitamin B12 metabolism, the late-onset form of the disease can be difficult to recognize because it has a broad phenotypic spectrum. In this report, we describe an adolescent female exposed to unknown illicit substances and sexual abuse who presented with psychosis, anorexia, seizures, and ataxia. The patient's diagnosis was delayed until a metabolic workup was initiated, revealing hyperhomocysteinemia, low normal plasma methionine, and methylmalonic aciduria. Ultimately, cblC deficiency was confirmed when molecular testing showed compound heterozygosity for mutations (c.271dupA and c.482G>A) in the MMACHC gene. This diagnosis led to appropriate treatment with hydroxocobalamin, betaine, and folate, which resulted in improvement of her clinical symptoms and laboratory values. This patient demonstrates a previously unrecognized presentation of late-onset cblC deficiency. Although neuropsychiatric symptoms are common in late-onset disease, seizures and cerebellar involvement are not. Furthermore, anorexia has not been previously described in these patients. This case emphasizes that inborn errors of metabolism should be part of the differential diagnosis for a teenager presenting with altered mental status, especially when the diagnosis is challenging or neurologic symptoms are unexplained. Correct diagnosis of this condition is important because treatment is available and can result in clinical improvement.(1.) Copyright © 2014 by the American Academy of Pediatrics.

Glucose-6-phosphate dehydrogenase deficiency in Nigerian children.

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Olatundun Williams

Full Text Available Glucose-6-phosphate dehydrogenase (G6PD deficiency is the most common human enzymopathy and in Sub-Saharan Africa, is a significant cause of infection- and drug-induced hemolysis and neonatal jaundice. Our goals were to determine the prevalence of G6PD deficiency among Nigerian children of different ethnic backgrounds and to identify predictors of G6PD deficiency by analyzing vital signs and hematocrit and by asking screening questions about symptoms of hemolysis. We studied 1,122 children (561 males and 561 females aged 1 month to 15 years. The mean age was 7.4 ± 3.2 years. Children of Yoruba ethnicity made up the largest group (77.5% followed by those Igbo descent (10.6% and those of Igede (10.2% and Tiv (1.8% ethnicity. G6PD status was determined using the fluorescent spot method. We found that the overall prevalence of G6PD deficiency was 15.3% (24.1% in males, 6.6% in females. Yoruba children had a higher prevalence (16.9% than Igede (10.5%, Igbo (10.1% and Tiv (5.0% children. The odds of G6PD deficiency were 0.38 times as high in Igbo children compared to Yoruba children (p=0.0500. The odds for Igede and Tiv children were not significantly different from Yoruba children (p=0.7528 and 0.9789 respectively. Mean oxygen saturation, heart rate and hematocrit were not significantly different in G6PD deficient and G6PD sufficient children. The odds of being G6PD deficient were 2.1 times higher in children with scleral icterus than those without (p=0.0351. In conclusion, we determined the prevalence of G6PD deficiency in Nigerian sub-populations. The odds of G6PD deficiency were decreased in Igbo children compared to Yoruba children. There was no association between vital parameters or hematocrit and G6PD deficiency. We found that a history of scleral icterus may increase the odds of G6PD deficiency, but we did not exclude other common causes of icterus such as sickle cell disease or malarial infection.

The Evidence-Based Evaluation of Iron Deficiency Anemia.

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Hempel, Eliana V; Bollard, Edward R

2016-09-01

Anemia is a prevalent disease with multiple possible etiologies and resultant complications. Iron deficiency anemia is a common cause of anemia and is typically due to insufficient intake, poor absorption, or overt or occult blood loss. Distinguishing iron deficiency from other causes of anemia is integral to initiating the appropriate treatment. In addition, identifying the underlying cause of iron deficiency is also necessary to help guide management of these patients. We review the key components to an evidence-based, cost-conscious evaluation of suspected iron deficiency anemia. Copyright © 2016 Elsevier Inc. All rights reserved.

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 ...

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.

Oxidative Olefination of Anilides with Unactivated Alkenes Catalyzed by an (Electron-Deficient η(5) -Cyclopentadienyl)Rhodium(III) Complex Under Ambient Conditions.

Science.gov (United States)

Takahama, Yuji; Shibata, Yu; Tanaka, Ken

2015-06-15

The oxidative olefination of sp(2) C-H bonds of anilides with both activated and unactivated alkenes using an (electron-deficient η(5) -cyclopentadienyl)rhodium(III) complex is reported. In contrast to reactions using this electron-deficient rhodium(III) catalyst, [Cp*RhCl2 ]2 showed no activity against olefination with unactivated alkenes. In addition, the deuterium kinetic isotope effect (DKIE) study revealed that the C-H bond cleavage step is thought to be the turnover-limiting step. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Vitamin D deficiency in early pregnancy.

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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.

Inflammatory Markers: C-Reactive Protein, Erythrocyte Sedimentation Rate, and Leukocyte Count in Vitamin D Deficient Patients with and without Chronic Kidney Disease

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Ibrahim Yildirim

2013-01-01

Full Text Available Although some studies revealed a positive relationship between vitamin D3 deficiency and inflammatory markers, there have been also many studies that failed to find this relationship. The aim of this large scaled study is to determine the association between the level of plasma 25 hydroxy vitamin D3 [25-(OH D3] and inflammatory markers in the general population without chronic kidney disease (CKD and in patients with CKD. Participants with simultaneously measured inflammatory markers and 25-(OH D3 levels were retrospectively analyzed (n=1897. The incidence of all-cause inflammation infection, hospitalization, chronic renal failure, and vitamin B12 deficiency was evaluated. The medians of serum creatinine levels in subjects without renal failure were lower in 25-(OH D3 deficient group. Patients with CKD were more likely to have vitamin D3 deficiency compared with normal GFR. 25-(OH D3 levels were associated with a greater incidence of all-cause hospitalization, hypoalbuminemia, and vitamin B12 deficiency. However, there was no relationship between inflammatory markers and vitamin D3 levels. In 25-(OH D3 deficient patients, inflammatory markers can be related to other inflammatory and infectious status such as malnutrition and cachexia. We believed that there must be a relationship between vitamin deficiency and inflammatory markers due to other causes than low 25-(OH D3 status.

Epidemiology of SHOX deficiency.

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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.

[Osteomalacia and vitamin D deficiency].

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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.

Hypopituitarism: growth hormone and corticotropin deficiency.

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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.

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 ...

Iron-Deficiency Anemia

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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 ...

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 ...

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...

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.

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)

Thyroid disorders in mild iodine deficiency.

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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.

LPIN1 deficiency with severe recurrent rhabdomyolysis and persistent elevation of creatine kinase levels due to chromosome 2 maternal isodisomy

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I.A. Meijer

2015-12-01

Full Text Available Fatty acid oxidation disorders and lipin-1 deficiency are the commonest genetic causes of rhabdomyolysis in children. We describe a lipin-1-deficient boy with recurrent, severe rhabdomyolytic episodes from the age of 4 years. Analysis of the LPIN1 gene that encodes lipin-1 revealed a novel homozygous frameshift mutation in exon 9, c.1381delC (p.Leu461SerfsX47, and complete uniparental isodisomy of maternal chromosome 2. This mutation is predicted to cause complete lipin-1 deficiency. The patient had six rhabdomyolytic crises, with creatine kinase (CK levels up to 300,000 U/L (normal, 30 to 200. Plasma CK remained elevated between crises. A treatment protocol was instituted, with early aggressive monitoring, hydration, electrolyte replacement and high caloric, high carbohydrate intake. The patient received dexamethasone during two crises, which was well-tolerated and in these episodes, peak CK values were lower than in preceding episodes. Studies of anti-inflammatory therapy may be indicated in lipin-1 deficiency.

T Cell Intrinsic USP15 Deficiency Promotes Excessive IFN-γ Production and an Immunosuppressive Tumor Microenvironment in MCA-Induced Fibrosarcoma

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Qiang Zou

2015-12-01

Full Text Available USP15 is a deubiquitinase that negatively regulates activation of naive CD4+ T cells and generation of IFN-γ-producing T helper 1 (Th1 cells. USP15 deficiency in mice promotes antitumor T cell responses in a transplantable cancer model; however, it has remained unclear how deregulated T cell activation impacts primary tumor development during the prolonged interplay between tumors and the immune system. Here, we find that the USP15-deficient mice are hypersensitive to methylcholantrene (MCA-induced fibrosarcomas. Excessive IFN-γ production in USP15-deficient mice promotes expression of the immunosuppressive molecule PD-L1 and the chemokine CXCL12, causing accumulation of T-bet+ regulatory T cells and CD11b+Gr-1+ myeloid-derived suppressor cells at tumor site. Mixed bone marrow adoptive transfer studies further reveals a T cell-intrinsic role for USP15 in regulating IFN-γ production and tumor development. These findings suggest that T cell intrinsic USP15 deficiency causes excessive production of IFN-γ, which promotes an immunosuppressive tumor microenvironment during MCA-induced primary tumorigenesis.

Factor V deficiency

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... 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 ...

Factor II deficiency

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... 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 ...

Factor X deficiency

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... 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 ...

Zinc deficiency-induced iron accumulation, a consequence of alterations in iron regulatory protein-binding activity, iron transporters, and iron storage proteins.

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Niles, Brad J; Clegg, Michael S; Hanna, Lynn A; Chou, Susan S; Momma, Tony Y; Hong, Heeok; Keen, Carl L

2008-02-22

One consequence of zinc deficiency is an elevation in cell and tissue iron concentrations. To examine the mechanism(s) underlying this phenomenon, Swiss 3T3 cells were cultured in zinc-deficient (D, 0.5 microM zinc), zinc-supplemented (S, 50 microM zinc), or control (C, 4 microM zinc) media. After 24 h of culture, cells in the D group were characterized by a 50% decrease in intracellular zinc and a 35% increase in intracellular iron relative to cells in the S and C groups. The increase in cellular iron was associated with increased transferrin receptor 1 protein and mRNA levels and increased ferritin light chain expression. The divalent metal transporter 1(+)iron-responsive element isoform mRNA was decreased during zinc deficiency-induced iron accumulation. Examination of zinc-deficient cells revealed increased binding of iron regulatory protein 2 (IRP2) and decreased binding of IRP1 to a consensus iron-responsive element. The increased IRP2-binding activity in zinc-deficient cells coincided with an increased level of IRP2 protein. The accumulation of IRP2 protein was independent of zinc deficiency-induced intracellular nitric oxide production but was attenuated by the addition of the antioxidant N-acetylcysteine or ascorbate to the D medium. These data support the concept that zinc deficiency can result in alterations in iron transporter, storage, and regulatory proteins, which facilitate iron accumulation.

Micronutrient deficiencies and gender: social and economic costs.

Science.gov (United States)

Darnton-Hill, Ian; Webb, Patrick; Harvey, Philip W J; Hunt, Joseph M; Dalmiya, Nita; Chopra, Mickey; Ball, Madeleine J; Bloem, Martin W; de Benoist, Bruno

2005-05-01

Vitamin and mineral deficiencies adversely affect a third of the world's people. Consequently, a series of global goals and a serious amount of donor and national resources have been directed at such micronutrient deficiencies. Drawing on the extensive experience of the authors in a variety of institutional settings, the article used a computer search of the published scientific literature of the topic, supplemented by reports and published and unpublished work from the various agencies. In examining the effect of sex on the economic and social costs of micronutrient deficiencies, the paper found that: (1) micronutrient deficiencies affect global health outcomes; (2) micronutrient deficiencies incur substantial economic costs; (3) health and nutrition outcomes are affected by sex; (4) micronutrient deficiencies are affected by sex, but this is often culturally specific; and finally, (5) the social and economic costs of micronutrient deficiencies, with particular reference to women and female adolescents and children, are likely to be considerable but are not well quantified. Given the potential impact on reducing infant and child mortality, reducing maternal mortality, and enhancing neuro-intellectual development and growth, the right of women and children to adequate food and nutrition should more explicitly reflect their special requirements in terms of micronutrients. The positive impact of alleviating micronutrient malnutrition on physical activity, education and productivity, and hence on national economies suggests that there is also an urgent need for increased effort to demonstrate the cost of these deficiencies, as well as the benefits of addressing them, especially compared with other health and nutrition interventions.

Leaf Volatile Compounds and Associated Gene Expression during Short-Term Nitrogen Deficient Treatments in Cucumis Seedlings

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Jie Deng

2016-11-01

Full Text Available Nitrogen (N is an important macronutrient for plant growth and development, but the regulatory mechanism of volatile compounds in response to N deficiency is not well understood, especially in cucumber, which consumes excessive N during growth. In this study, the major volatile compounds from cucumber leaves subjected to N deficiency were analyzed by GC-MS. A total of 24 volatile components were identified including 15 aldehydes, two ketones, two alkenes, and five other volatile compounds in 9930 leaves. Principal component analysis using volatile compounds from cucumber leaves provided good separation between N-sufficient and N-deficient treatments. The main volatiles in cucumber leaves were found to be C6 and C9 aldehydes, especially (E-2-hexanal and (E,Z-2,6-nonadienal. (E-2-hexanal belonged to the C6 aldehyde and was the most abundant compound, whereas (E,Z-2,6-nonadienal was the chief component of C9 aldehydes. During N-deficient treatment, short-chain volatile content was significantly improved at 5 day, other volatiles displayed significant reduction or no significantly changes in all sampling points. Improvement of short-chain volatiles was confirmed in the six other inbred lines at 5 day after N-deficient treatments. The expression analysis of 12 cucumber LOX genes and two HPL genes revealed that CsLOX19, CsLOX20, and CsLOX22 had common up-regulated expression patterns in response to N-deficient stress in most inbred lines; meanwhile, most sample points of CsHPL1 also had significant up-regulated expression patterns. This research focused on the relationship between volatiles in cucumber and different nitrogen environments to provide valuable insight into the effect of cultivation and management of the quality of cucumber and contributes to further research on volatile metabolism in cucumber.

The effects of ionizing radiation in the rat's mandibular bone freeding the hypernomic calcium-deficient diet

International Nuclear Information System (INIS)

Hasegawa, Gen; Kurita, Akihiko; Nasu, Masanori; Furumoto, Keiichi

1994-01-01

The mandibles of rats in a group maintained on the Ca-deficient diet for a long period were irradiated with 30 Gy. To study the effects of radiation, serum Ca and inorganic phosphorus levels were determined for 3 weeks, and the data were compared with findings obtained from rats maintained on a standard diet by autoradiography using 45 Ca and microradiography. The serum Ca level tended to decrease with time after irradiation in the irradiated group maintained on the Ca-deficient diet, but there was no significant difference between the group maintained on the Ca-deficient diet and the group maintained on the standard diet. The serum inorganic phosphorus levels were almost constant throughout the observation period in both the non-irradiated and radiated groups regardless of diet. Uptake of 45 Ca was examined by autoradiography. Both the non-irradiated and irradiated groups maintained on the Ca-deficient diet showed intense 45 Ca uptake, there was almost no difference between these groups in photographic density or in weekly changes after irradiation. The microradiographic study of bone trabeculae revealed only slight changes in the bone cortex after irradiation in the group maintained on the standard diet. On day 3 after irradiation both thinning and roughness of the trabeculae were observed in the interradicular septa and incisal inferior margin and on day 7 in cancellous bone. In the groups maintained on the Ca-deficient diet, marked thinning and roughness of the trabeculae were observed mainly in the cancellous bone. (author)

Reference: 475 [Arabidopsis Phenome Database[Archive

Lifescience Database Archive (English)

Full Text Available n higher plants, we analyze two knock-out and one knock-down T-DNA insertion mutants. The knock...-out mutants present an embryo-lethal phenotype, indicating an essential role for frataxin. The knock

Clinical, Immunological, and Molecular Findings in Five Patients with Major Histocompatibility Complex Class II Deficiency from India

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Jahnavi Aluri

2018-02-01

Full Text Available Major histocompatibility complex (MHC class II deficiency is a rare autosomal recessive form of primary immunodeficiency disorder (PID characterized by the deficiency of MHC class II molecules. This deficiency affects the cellular and humoral immune response by impairing the development of CD4+ T helper (Th cells and Th cell-dependent antibody production by B cells. Affected children typically present with severe respiratory and gastrointestinal tract infections. Hematopoietic stem cell transplantation (HSCT is the only curative therapy available for treating these patients. This is the first report from India wherein we describe the clinical, immunological, and molecular findings in five patients with MHC class II deficiency. Our patients presented with recurrent lower respiratory tract infection as the most common clinical presentation within their first year of life and had a complete absence of human leukocyte antigen-antigen D-related (HLA-DR expression on B cells and monocytes. Molecular characterization revealed novel mutations in RFAXP, RFX5, and CIITA genes. Despite genetic heterogeneity, these patients were clinically indistinguishable. Two patients underwent HSCT but had a poor survival outcome. Detectable level of T cell receptor excision circles (TRECs were measured in our patients, highlighting that this form of PID may be missed by TREC-based newborn screening program for severe combined immunodeficiency.

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 ...

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 ...

Toll-like receptor 2 deficiency leads to delayed exacerbation of ischemic injury

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Bohacek Ivan

2012-08-01

Full Text Available Abstract Background Using a live imaging approach, we have previously shown that microglia activation after stroke is characterized by marked and long-term induction of the Toll-like receptor (TLR 2 biophotonic signals. However, the role of TLR2 (and potentially other TLRs beyond the acute innate immune response and as early neuroprotection against ischemic injury is not well understood. Methods TLR2−/− mice were subjected to transient middle cerebral artery occlusion followed by different reperfusion times. Analyses assessing microglial activation profile/innate immune response were performed using in situ hybridization, immunohistochemistry analysis, flow cytometry and inflammatory cytokine array. The effects of the TLR2 deficiency on the evolution of ischemic brain injury were analyzed using a cresyl violet staining of brain sections with appropriate lesion size estimation. Results Here we report that TLR2 deficiency markedly affects post-stroke immune response resulting in delayed exacerbation of the ischemic injury. The temporal analysis of the microglia/macrophage activation profiles in TLR2−/− mice and age-matched controls revealed reduced microglia/macrophage activation after stroke, reduced capacity of resident microglia to proliferate as well as decreased levels of monocyte chemotactic protein-1 (MCP-1 and consequently lower levels of CD45high/CD11b+ expressing cells as shown by flow cytometry analysis. Importantly, although acute ischemic lesions (24 to 72 h were smaller in TLR2−/− mice, the observed alterations in innate immune response were more pronounced at later time points (at day 7 after initial stroke, which finally resulted in delayed exacerbation of ischemic lesion leading to larger chronic infarctions as compared with wild-type mice. Moreover, our results revealed that TLR2 deficiency is associated with significant decrease in the levels of neurotrophic/anti-apoptotic factor Insulin-like growth factor-1 (IGF-1

SECONDARY LACTASE DEFICIENCY AND ITS CORRECTION IN INFANTS ILL WITH ROTAVIRUS INFECTION

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Kirsanova TA

2016-12-01

Full Text Available Introduction. Cardinal changes in medicine during recent years have made the problem of disorders in digestion and carbohydrate absorption one of the most crucial. Lactose intolerance (lactase deficiency is a clinically revealed inability of intestinal enzymatic systems to break down lactose, where secondary lactose deficiency results from damage of erythrocytes against a background of some disease, including that of an infectious origin, particularly in viral intestinal infections. Purpose of the study. To study the efficacy of taking lactase preparations by infants during the first year of their life, who are breast fed and ill with rotavirus infection. Materials and methods. The study involved 28 naturally fed infants of the first year of life with rotavirus infection. The diagnosis was made by revealing the virus antigen in the patients’ faeces and antibodies to it in their blood. Besides the standard methods of examination the faeces were analysed for carbohydrates and pH values. The patients were divided into two groups: the first group of infants did not receive lactase-containing drugs in their combined therapy; the second group took them. Results. Damage of the gastrointestinal tract of the retrovirus aetiology was characterized by the following signs: vomiting, abdominal distention, diarrhoea with watery frothy stool having sour odour and undigested boluses. In the group of infants, whose combined therapy used lactase-containing drugs, regression of their clinical signs passed reliably more rapidly than in the group of infants, who did not receive the above medicines. Conclusion. The use of lactase-containing preparations in the treatment of infants, who are breast fed and ill with rotavirus infection, is undoubtedly effective in order to correct lactase deficiency, since it causes a more rapid disappearance of clinical manifestations of the disease, thereby making it possible to examine the possible inclusion of these drugs into the

Sulfur amino acids metabolism in magnesium deficient rats

Energy Technology Data Exchange (ETDEWEB)

Tojo, H.; Kosokawa, Y.; Yamaguchi, K.

1984-01-01

Effect of magnesium (Mg) deficiency on sulfur amino acid metabolism was investigated in rats. Young male rats were fed on the diet containing either 2.26 (deficient rats) or 63.18 mg Mg/100g diet (control and low protein rats) for 2 weeks. A remarkable decrease of body weight gain, serum Mg contents and a slight decreases in the hematological parameters such as Hb, Ht and RBC was observed, while the hepatic Mg and Ca was not significantly changed. Erythema and cramps were observed 5 days after feeding on the Mg-depleted diet. The hepatic glutathione and cysteine contents increased in Mg-deficient rats. However, no significant change of cysteine dioxygenase (CDO) activity and taurine content in Mg-deficient rat liver was observed. These results suggest that Mg deficiency affects the utilization and biosynthesis of hepatic glutathione but not the cysteine catabolism.

Environmental Stresses of Field Growth Allow Cinnamyl Alcohol Dehydrogenase-Deficient Nicotiana attenuata Plants to Compensate for their Structural Deficiencies1[C][W][OA

Science.gov (United States)

Kaur, Harleen; Shaker, Kamel; Heinzel, Nicolas; Ralph, John; Gális, Ivan; Baldwin, Ian T.

2012-01-01

The organized lignocellulosic assemblies of cell walls provide the structural integrity required for the large statures of terrestrial plants. Silencing two CINNAMYL ALCOHOL DEHYDROGENASE (CAD) genes in Nicotiana attenuata produced plants (ir-CAD) with thin, red-pigmented stems, low CAD and sinapyl alcohol dehydrogenase activity, low lignin contents, and rubbery, structurally unstable stems when grown in the glasshouse (GH). However, when planted into their native desert habitat, ir-CAD plants produced robust stems that survived wind storms as well as the wild-type plants. Despite efficient silencing of NaCAD transcripts and enzymatic activity, field-grown ir-CAD plants had delayed and restricted spread of red stem pigmentation, a color change reflecting blocked lignification by CAD silencing, and attained wild-type-comparable total lignin contents. The rubbery GH phenotype was largely restored when field-grown ir-CAD plants were protected from wind, herbivore attack, and ultraviolet B exposure and grown in restricted rooting volumes; conversely, it was lost when ir-CAD plants were experimentally exposed to wind, ultraviolet B, and grown in large pots in growth chambers. Transcript and liquid chromatography-electrospray ionization-time-of-flight analysis revealed that these environmental stresses enhanced the accumulation of various phenylpropanoids in stems of field-grown plants; gas chromatography-mass spectrometry and nuclear magnetic resonance analysis revealed that the lignin of field-grown ir-CAD plants had GH-grown comparable levels of sinapaldehyde and syringaldehyde cross-linked into their lignins. Additionally, field-grown ir-CAD plants had short, thick stems with normal xylem element traits, which collectively enabled field-grown ir-CAD plants to compensate for the structural deficiencies associated with CAD silencing. Environmental stresses play an essential role in regulating lignin biosynthesis in lignin-deficient plants. PMID:22645069

Hepatic lipidosis associated with cobalt deficiency in Omani goats.

Science.gov (United States)

Johnson, E H; Muirhead, D E; Annamalai, K; King, G J; Al-Busaidy, R; Hameed, M S

1999-06-01

Livers from 36 of 684 (5.3%) apparently healthy goats examined at an abattoir in the greater Muscat area of Oman exhibited gross pathological findings characterized by extremely pale, friable, fatty livers encompassing the entire organ. Histopathologically, diffuse hepatic lipidosis and occasional bile duct proliferation were observed. Periodic acid Schiff-positive, diastase-resistant pigment was observed in the macrophages lining the sinusoids. These histopathological lesions were consistent with those characteristic of ovine white liver disease. Cobalt analysis revealed that normal livers had six times more cobalt and a 3-fold less fat content than those measured in the fatty livers. This is the first report of an association between cobalt deficiency and hepatic lipidosis in Omani goats.

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

Clinical, genetic, and structural basis of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency.

Science.gov (United States)

Khattab, Ahmed; Haider, Shozeb; Kumar, Ameet; Dhawan, Samarth; Alam, Dauood; Romero, Raquel; Burns, James; Li, Di; Estatico, Jessica; Rahi, Simran; Fatima, Saleel; Alzahrani, Ali; Hafez, Mona; Musa, Noha; Razzghy Azar, Maryam; Khaloul, Najoua; Gribaa, Moez; Saad, Ali; Charfeddine, Ilhem Ben; Bilharinho de Mendonça, Berenice; Belgorosky, Alicia; Dumic, Katja; Dumic, Miroslav; Aisenberg, Javier; Kandemir, Nurgun; Alikasifoglu, Ayfer; Ozon, Alev; Gonc, Nazli; Cheng, Tina; Kuhnle-Krahl, Ursula; Cappa, Marco; Holterhus, Paul-Martin; Nour, Munier A; Pacaud, Daniele; Holtzman, Assaf; Li, Sun; Zaidi, Mone; Yuen, Tony; New, Maria I

2017-03-07

Congenital adrenal hyperplasia (CAH), resulting from mutations in CYP11B1 , a gene encoding 11β-hydroxylase, represents a rare autosomal recessive Mendelian disorder of aberrant sex steroid production. Unlike CAH caused by 21-hydroxylase deficiency, the disease is far more common in the Middle East and North Africa, where consanguinity is common often resulting in identical mutations. Clinically, affected female newborns are profoundly virilized (Prader score of 4/5), and both genders display significantly advanced bone ages and are oftentimes hypertensive. We find that 11-deoxycortisol, not frequently measured, is the most robust biochemical marker for diagnosing 11β-hydroxylase deficiency. Finally, computational modeling of 25 missense mutations of CYP11B1 revealed that specific modifications in the heme-binding (R374W and R448C) or substrate-binding (W116C) site of 11β-hydroxylase, or alterations in its stability (L299P and G267S), may predict severe disease. Thus, we report clinical, genetic, hormonal, and structural effects of CYP11B1 gene mutations in the largest international cohort of 108 patients with steroid 11β-hydroxylase deficiency CAH.

GM2-ganglioside metabolism in hexosaminidase A deficiency states: determination in situ using labeled GM2 added to fibroblast cultures

International Nuclear Information System (INIS)

Raghavan, S.S.; Krusell, A.; Krusell, J.; Lyerla, T.A.; Kolodny, E.H.

1985-01-01

To clarify the relationship between hexosaminidase A (HEX A) activity and GM2-ganglioside hydrolysis in atypical clinical situations of HEX A deficiency, we have developed a simple method to assess GM2-ganglioside metabolism in cultured fibroblasts utilizing GM2 labeled with tritium in the sphingosine portion of the molecule. The radioactive lipid is added to the media of cultured skin fibroblasts, and after 10 days the cells are thoroughly washed, then harvested, and their lipid composition analyzed by HPLC. The degree of hydrolysis of the ingested GM2 is determined by comparing the amount of radioactive counts recovered in undegraded substrate with total cellular radioactivity. A deficiency in GM2-ganglioside hydrolysis was demonstrated in seven HEX A-deficient adults with neurological signs and in two healthy-appearing adolescents with older affected siblings. In each case, an analysis of endogenous monosialoganglioside composition revealed an increase in GM2-ganglioside, confirming the presence of a block in the metabolism of GM2. No defect in GM2-catabolism was found in four other healthy individuals with HEX A deficiency. This method of assay is especially helpful in the evaluation of atypical cases of HEX A deficiency for the definitive diagnosis of GM2-gangliosidosis

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

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 ...

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 ...

Increased uracil misincorporation in lymphocytes from folate-deficient rats

OpenAIRE

Duthie, S J; Grant, G; Narayanan, S

2000-01-01

The development of certain human cancers has been linked with inadequate intake of folates. The effects of folate deficiency in vivo on DNA stability (strand breakage, misincorporated uracil and oxidative base damage) in lymphocytes isolated from rats fed a diet deficient in folic acid was determined. Because the metabolic pathways of folate and other methyl donors are closely coupled, the effects of methionine and choline deficiency alone or in combination with folate deficiency were determi...

Homocysteine and vitamin B 12 status and iron deficiency anemia in female university students from Gaza Strip, Palestine

Directory of Open Access Journals (Sweden)

Mahmoud Mohammed Sirdah

2014-06-01

Full Text Available OBJECTIVE: Nutritional deficiencies are very significant to the overall health of humans at all ages and for both genders, yet in infants, children and women of childbearing age these deficiencies can seriously affect growth and development. The present work is aimed to assess homocysteine and vitamin B12 status in females with iron deficiency anemia from the Gaza Strip.METHODS: Venous blood samples were randomly collected from 240 female university students (18-22 years old and parameters of the complete blood count, serum ferritin, homocysteine and vitamin B12 were measured. Statistical analysis included the t-test and analysis of variance (ANOVA using the IBM SPSS software (version 18. Statistical significance was set for p-values <0.05.RESULTS: The results revealed that 20.4% of the students have iron deficiency anemia. The mean serum vitamin B12 level in females with iron deficiency anemia (212.9 ± 62.8 pg/mL was significantly lower than in normal controls (286.9 ± 57.1 pg/mL and subjects with microcytic anemia and normal ferritin (256.7 ± 71.1 pg/mL. Significantly higher serum homocysteine levels were reported in the iron deficiency anemia group (27.0 ± 4.6 µmol/L compared to normal controls (15.5 ± 2.9 µmol/L and in subjects with microcytic anemia and normal ferritin (18.1 ± 2.7 µmol/L. Statistically significant negative correlations were reported for serum homocysteine with serum ferritin, vitamin B12, hemoglobin, and hematocrit levels.CONCLUSION: Important associations were found between serum homocysteine and markers of iron deficiency. Monitoring homocysteine levels might be essential to understand the development of different clinical conditions including anemia. It seems necessary to conduct prospective trials to determine whether treating anemia ameliorates homocysteine levels.

Investigation of ferromagnetism in oxygen deficient hafnium oxide thin films

Energy Technology Data Exchange (ETDEWEB)

Hildebrandt, Erwin; Kurian, Jose; Krockenberger, Yoshiharu; Alff, Lambert [Institut fuer Materialwissenschaft, TU Darmstadt (Germany); Suter, Andreas [PSI, Villingen (Switzerland); Wilhelm, Fabrice; Rogalev, Andrei [ESRF, Grenoble (France)

2008-07-01

Oxygen deficient thin films of hafnium oxide were grown on single crystal r-cut and c-cut sapphire by reactive molecular beam epitaxy. RF-activated oxygen was used for the in situ oxidation of hafnium oxide thin films. Oxidation conditions were varied substantially in order to create oxygen deficiency in hafnium oxide films intentionally. The films were characterized by X-ray and magnetic measurements. X-ray diffraction studies show an increase in lattice parameter with increasing oxygen deficiency. Oxygen deficient hafnium oxide thin films also showed a decreasing bandgap with increase in oxygen deficiency. The magnetisation studies carried out with SQUID did not show any sign of ferromagnetism in the whole oxygen deficiency range. X-ray magnetic circular dichroism measurements also confirmed the absence of ferromagnetism in oxygen deficient hafnium oxide thin films.

[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.

Estudo de prevalência em recém-nascidos por deficiência de biotinidase Neonatal screening for biotinidase deficiency

Directory of Open Access Journals (Sweden)

Anna L. R. Pinto

1998-04-01

Full Text Available INTRODUÇÃO: A deficiência de biotinidase é um erro inato do metabolismo caracterizado principalmente por ataxia, crise convulsiva retardo mental, dermatites, alopécia e susceptibilidade a infecções. É atribuída a esta deficiência enzimática a forma tardia de deficiência múltipla das carboxilases. Com o objetivo de verificar a prevalência da deficiência de biotinidase e validar o teste de triagem neonatal considerando a relação custo/benefício, elaborou-se estudo prospectivo na população de recém-nascidos no Estado do Paraná. MATERIAL E MÉTODO: Em um período de 8 meses foram triados 125.000 recém-nascidos. A amostra sangüínea foi a mesma obtida para os testes de triagem para fenilcetonúria e hipotireoidismo congênito, submetida ao teste semiquantitativo colorimétrico para atividade de biotinidase. As amostras consideradas suspeitas foram repetidas em duplicatas do mesmo cartão de papel de filtro, e as que permaneceram alteradas solicitou-se novo cartão. O teste quantitativo colorimétrico da doença foi realizado nos casos em que a segunda amostra testada em duplicata sugeriu deficiência de biotinidase. RESULTADOS: A taxa de repetição em duplicata variou de 0,9% a 0,5% do total de exames realizados por mês. A taxa de reconvocação do segundo cartão foi de 0,17%, sendo que destes 212 casos, 30% não retornaram o segundo cartão solicitado. Foram identificados 2 casos, um de deficiência total de biotinidase e outro de deficiência parcial. A prevalência da doença na população de estudo foi de 1:62.500 nascidos-vivos. A sensibilidade do teste semiquantativo colorimétrico foi calculada em 100% e a especificidade 99,88%. CONCLUSÃO: A prevalência da doença no Estado do Paraná foi de 1:125.000 nascidos-vivos para deficiência total da enzima, levando-se em consideração que 30% de casos suspeitos que repetiram novo teste. O teste semiquantitativo colorimétrico foi considerado efetivo em identificar os

Characterization and Selection of Phosphorus Deficiency Tolerant Rice Genotypes in Sri Lanka

Directory of Open Access Journals (Sweden)

Y.C. Aluwihare

2016-07-01

Full Text Available Phosphorus (P deficiency in soil is a major constrain for rice production. An important set of rice genotypes (landraces, old improved and new improved varieties were screened for P deficiency tolerance in two major cropping seasons of Sri Lanka, in 2012. The Ultisol soil, which was collected from a plot cultivated with rice without fertilizer application for past 40 years (P0 at the Rice Research and Development Institute (RRDI, Bathalagoda, Sri Lanka, was used as the potting medium for greenhouse trials. Two field trials were conducted in the same plots at RRDI. Both P0 and P30 (30 mg/kg P2O5 conditions were used in the two greenhouse trials. At the early vegetative (three weeks after transplanting, late vegetative (six weeks after transplanting and flowering stages, plant height and number of tillers per plant were recorded. At the flowering stage, shoots were harvested and shoot dry weight, shoot P concentration, shoot P uptake and P utilization efficiency were measured. All data were statistically analyzed using analysis of variance, regression and cluster procedures. The measured parameters were significantly different between P0 and P30 conditions (P < 0.05. Higher shoot dry weight was reported by the rice genotypes H4 and Marss under P0 conditions. The regression analysis between shoot dry weight and P utilization efficiency revealed that the studied rice genotypes could be categorized to three P deficiency tolerance classes. A total of 13 genotypes could be considered as highly tolerant and 4 genotypes as sensitive for P deficiency. These results could be used to select parental genotypes for breeding and genetic studies and also to select interesting varieties or landraces for organic rice production.

Iron-Deficiency Anemia

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