Sample records for hb viii proton-capture

  1. Microchromatography of hemoglobins. VIII. A general qualitative and quantitative method in plastic drinking straws and the quantitative analysis of Hb-F. (United States)

    Schroeder, W A; Pace, L A


    The microchromatographic procedure for the quantitative analysis of the hemoglobin components in a hemolysate uses columns of DEAE-cellulose in a plastic drinking straw with a glycine-KCN-NaCl developer. Not only may the method be used for the quantitative analysis of Hb-F but also for the analysis of the varied components in mixtures of hemoglobins.

  2. Measurement of proton capture reactions in the hot cycles: an evaluation of experimental methods

    Energy Technology Data Exchange (ETDEWEB)

    Leleux, P. [Inst. de Physique Nucleaire, Univ. Catholique de Louvain, Louvain-la-Neuve (Belgium)


    In the hot cycles, most of the proton capture reactions involve radioactive nuclei in the entrance and exit channels. This paper evaluates the specific methods that were designed to measure such reactions. (orig.)

  3. Systematic study of proton capture rates for Mo and Cd isotopes

    Energy Technology Data Exchange (ETDEWEB)

    Bajpeyi, Awanish; Shukla, A. [Rajiv Gandhi Institute of Petroleum Technology, Department of Physics, Raebareli (India); Koning, A.J. [Nuclear Research and Consultancy Group NRG, Petten (Netherlands); Aaberg, Sven [Lund University, Mathematical Physics, P.O. Box 118, Lund (Sweden)


    Proton capture reactions play a very important role in the understanding of nucleosynthesis. In the present work, p-capture reactions have been studied coherently with nuclear structure for the nuclei under consideration. We have calculated proton capture cross sections and S-factor for relevant isotopes of molybdenum and cadmium in the energy range 2.0 to 4.5 Mev. Calculated results for nuclear structure as well reaction rates are compared with the available experimental and theoretical results and are found to be in good agreement. (orig.)

  4. Systematic study of proton capture rates for Mo and Cd isotopes (United States)

    Bajpeyi, Awanish; Koning, A. J.; Shukla, A.; Åberg, Sven


    Proton capture reactions play a very important role in the understanding of nucleosynthesis. In the present work, p-capture reactions have been studied coherently with nuclear structure for the nuclei under consideration. We have calculated proton capture cross sections and S-factor for relevant isotopes of molybdenum and cadmium in the energy range 2.0 to 4.5 Mev. Calculated results for nuclear structure as well reaction rates are compared with the available experimental and theoretical results and are found to be in good agreement.

  5. p-process nucleosynthesis via proton-capture reactions in thermonuclear supernovae explosions

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    Endres Anne


    Full Text Available Model calculations within the framework of the so-called γ process show an underproduction of the p nucleus with the highest isotopic abundace 92Mo. This discrepancy can be narrowed by taking into account the alternative production site of a type Ia supernova explosion. Here, the nucleus 92Mo can be produced by a sequence of proton-capture reactions. The amount of 92Mo nuclei produced via this reaction chain is most sensitive to the reactions 90Zr(p,γ and 91Nb(p,γ. Both rates have to be investigated experimentally to study the impact of this nucleosynthesis aspect on the long-standing 92Mo-problem. We have already measured the proton-capture reaction on 90Zr using high-resolution in-beam γ-ray spectroscopy. In this contribution, we will present our preliminary results of the total cross sections as well as the partial cross sections. Furthermore, we plan to measure the 91Nb(p,γ reaction soon. Due to the radioactive target material, the 91Nb nuclei have to be produced prior to the experiment. The current status of this production will be presented in this contribution.

  6. Haemophilus influenzae biotype VIII.


    Sottnek, F O; Albritton, W L


    Six Haemophilus influenzae strains could not be classified as biotypes I through VII. The strains were indole, urease, and ornithine decarboxylase negative. We propose that they be classified as biotype VIII, a previously unreported biotype.

  7. Diagnosis of factor VIII deficiency.

    NARCIS (Netherlands)

    Verbruggen, B.; Meijer, P.; Novakova, I.; Heerde, W. Van


    The correct diagnosis of factor VIII deficiency and the assessment of severity of the disease are essential for a patient-tailored treatment strategy. An optimal diagnostic procedure comprises sensitive and specific screening methods and factor VIII activity assays. Different screening reagents show

  8. Contribution of Proton Capture Reactions to the Ascertained Abundance of Fluorine in the Evolved Stars of Globular Cluster M4, M22, 47 Tuc and NGC 6397 (United States)

    Mahanta, Upakul; Goswami, Aruna; Duorah, H. L.; Duorah, K.


    The origin of the abundance pattern and also the (anti)correlation present among the elements found in stars of globular clusters (GCs) remains unimproved until date. The proton-capture reactions are presently recognised in concert of the necessary candidates for that sort of observed behaviour in the second generation stars. We tend to propose a reaction network of a nuclear cycle namely carbon-nitrogen-oxygen-fluorine (CNOF) at evolved stellar condition since fluorine (^{19}F) is one such element which gets plagued by proton capture reactions. The stellar temperature thought about here ranges from 2× 107 to 10× 107 K and there has been an accretion occuring, with material density being 102 g/cm3 and 103 g/cm3. Such kind of temperature density conditions are probably going to be prevailing within the H-burning shell of evolved stars. The estimated abundances of ^{19}F are then matched with the info that has been determined for a few some metal-poor giants of GC M4, M22, 47 Tuc as well as NGC 6397. As far as the comparison between the observed and calculated abundances is concerned, it is found that the abundance of ^{19}F have shown an excellent agreement with the observed abundances with a correlation coefficent above 0.9, supporting the incidence of that nuclear cycle at the adopted temperature density conditions.

  9. Hb Cervantes, Hb Marañón, Hb La Mancha and Hb Goya: Description of 4 new haemoglobinopathies. (United States)

    de la Fuente-Gonzalo, Félix; Nieto, Jorge M; Ricard, Pilar; Anguita, Javier; Martínez, Rosalina; Cervera, Aurea; Villegas, Ana; González, Fernando A; Ropero, Paloma


    α-thalassemias are caused by a deficiency in or absence of synthesis of the α-chain of haemoglobin (Hb). In contrast, structural haemoglobinopathies are due to mutations that change the amino acid sequence of the protein chain. We report 4 newly identified α-chain Hb variants. Two variants were hyper-unstable, whereas the other 2 were structural variants with an altered electrophoretic mobility. The first 2 families were identified because of microcytosis and hypochromia with a normal Hb A2 and Hb F but without iron deficiency. The other 2 families came to scrutiny because of a peak of abnormal Hb during routine analytical assays. These Hb variants were characterized by specific sequencing. The hyper-instability of Hb Cervantes is probably due to its lower affinity for the alpha chain haemoglobin-stabilizing protein (AHSP). Hb Marañón is another unstable Hb variant that produces an α-thalassemia phenotype. For the identification of Hb La Mancha, a molecular characterization by sequencing was required. Finally, Hb Goya was found to have the same electrophoretic mobility as Hb J. A lower percentage of the variant was obtained due to a possible component of instability, though the patient did not show evidence of anaemia. These variants of Hb add to the variety and complexity of disorders of the genes that encode Hb. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  10. Diagnosis of factor VIII deficiency. (United States)

    Verbruggen, B; Meijer, P; Novákova, I; Van Heerde, W


    The correct diagnosis of factor VIII deficiency and the assessment of severity of the disease are essential for a patient-tailored treatment strategy. An optimal diagnostic procedure comprises sensitive and specific screening methods and factor VIII activity assays. Different screening reagents show variable characteristics and receiver operator characteristic curves are presented showing the relation between sensitivity and specificity of eleven activated partial thromboplastin time reagents. The details of the three methods for factor VIII activity assay, one-stage and two-stage assay and chromogenic assays, are discussed. The chromogenic assay seems to be more sensitive than the one-stage assay with regard to the detection of severe haemophilia. Discrepant results obtained with one-stage and two-stage assays are reviewed and discussed.

  11. Measuring the partial width of the 56Ni proton-capture resonance through (d,n) with VANDLE and MoNA-LISA (United States)

    Peters, William; Grzywacz, R.; Madurga, M.; Paulauskas, S.; Taylor, S.; Allen, J.; Cizewski, J. A.; Manning, B.; Howard, M. E.; Bardayan, D. W.; Pain, S. D.; Clement, R. C. C.; Ilyushkin, S.; O'Malley, P. D.; Ikeyama, R.; Kozub, R. L.; Long, K. D.; Bergstrom, Z. J.; Deyoung, P. A.; Rogers, W. F.; Smith, J.; Jones, M.; Baumann, T.; Thoennessen, M.; Vandle; Mona Collaboration


    Due to the long half-life of 56Ni and the low proton threshold of 57Cu, the (p, γ) reaction on 56Ni is the linchpin reaction for heavier elements in the rp process of explosive nucleosynthesis. A new attempt to measure the proton partial width of the excited 1/2- state in 57Cu and to indirectly extract the proton-capture resonance strength was performed at the National Superconducting Cyclotron Laboratory using the Versatile Array of Neutron Detectors at Low Energy (VANDLE) along with the MoNA-LISA neutron array. The VANDLE setup of digitizing electronics was event-matched to the MoNA-LISA-Sweeper data acquisition system. After a test run with a stable 40Ca beam, a beam of 56Ni impinged onto a deuterated polyethylene target inducing (d,n) transfer reactions to predominantly single-proton states in 57Cu. These experiments were the commissioning experiments for VANDLE with a transfer reaction. Details of the unique experimental setup will be presented as well as current analysis of the data with both 40Ca and 56Ni beams. Work supported in part by the USDoE Office of Science and the National Nuclear Security Administration Stewardship Science Academic Alliance and the National Science Foundation.

  12. Compound heterozygosity for Hb S and Hb S-Oman (United States)

    Venugopal, Suresh; Shaju, Alphonsa; Dhuri, Suchata; Al-Harthy, Thuraiya; Jabal, Khalid B


    The haematological and clinical findings of a three year old Omani girl, phenotypically compound heterozygote for Hb S and Hb S Oman, are presented, further substantiated by family studies. The necessity of reviewing cases with sickle cell haemoglobin in Oman is stressed. PMID:21748082

  13. Reactions of sulfur-nitrosyl iron complexes of "g=2.03" family with hemoglobin (Hb): kinetics of Hb-NO formation in aqueous solutions. (United States)

    Sanina, N A; Syrtsova, L A; Shkondina, N I; Rudneva, T N; Malkova, E S; Bazanov, T A; Kotel'nikov, A I; Aldoshin, S M


    NO-donating ability of nitrosyl [Fe-S] complexes, namely, mononuclear dinitrosyl complexes of anionic type [Fe(S2O3)2(NO)2]-(I) and neutral [Fe2(SL1)2(NO)2] with L1=1H-1,2,4-triazole-3-yl (II); tetranitrosyl binuclear neutral complexes [Fe2(SL2)2(NO)4] with L2=5-amino-1,2,4-triazole-3-yl (III); 1-methyl-1H-tetrazole-5-yl (IV); imidazole-2-yl (V) and 1-methyl-imidazole-2-yl (VI) has been studied. In addition, Roussin's "red salt" Na2[Fe2S2(NO)4] x 8H2O (VII) and Na2[Fe(CN)5NO] x H2O (VIII) have been investigated. The method for research has been based on the formation of Hb-NO adduct upon the interaction of hemoglobin with NO generated by complexes I-VIII in aqueous solutions. Kinetics of NO formation was studied by registration of absorption spectra of the reaction systems containing Hb and the complex under study. For determination of HbNO concentration, the experimental absorption spectra were processed during the reaction using standard program MATHCAD to determine the contribution of individual Hb and HbNO spectra in each spectrum. The reaction rate constants were obtained by analyzing kinetic dependence of Hb interaction with NO donors under study. All kinetic dependences for complexes I-VI were shown to be described well in the frame of formalism of pseudo first-order reactions. The effective first-order rate constants for the studied reactions have been determined. As follows from the values of rate constants, the rate of interaction of sulfur-nitrosyl iron complexes (I-VI) with Hb is limited by the stage of NO release in the solution.

  14. Baseline Report on HB2320 (United States)

    State Council of Higher Education for Virginia, 2015


    Staff provides this baseline report as a summary of its preliminary considerations and initial research in fulfillment of the requirements of HB2320 from the 2015 session of the General Assembly. Codified as § 23-7.4:7, this legislation compels the Education Secretary and the State Council of Higher Education for Virginia (SCHEV) Director, in…

  15. Effects of hemoglobin (Hb) E and HbD traits on measurements of glycated Hb (HbA1c) by 23 methods. (United States)

    Little, Randie R; Rohlfing, Curt L; Hanson, Steve; Connolly, Shawn; Higgins, Trefor; Weykamp, Cas W; D'Costa, Mario; Luzzi, Veronica; Owen, William E; Roberts, William L


    Glycohemoglobin (GHB), reported as hemoglobin (Hb) A(1c), is a marker of long-term glycemic control in patients with diabetes and is directly related to risk for diabetic complications. HbE and HbD are the second and fourth most common Hb variants worldwide. We investigated the accuracy of HbA(1c) measurement in the presence of HbE and/or HbD traits. We evaluated 23 HbA(1c) methods; 9 were immunoassay methods, 10 were ion-exchange HPLC methods, and 4 were capillary electrophoresis, affinity chromatography, or enzymatic methods. An overall test of coincidence of 2 least-squares linear regression lines was performed to determine whether the presence of HbE or HbD traits caused a statistically significant difference from HbAA results relative to the boronate affinity HPLC comparative method. Deming regression analysis was performed to determine whether the presence of these traits produced a clinically significant effect on HbA(1c) results with the use of +/-10% relative bias at 6% and 9% HbA(1c) as evaluation limits. Statistically significant differences were found in more than half of the methods tested. Only 22% and 13% showed clinically significant interference for HbE and HbD traits, respectively. Some current HbA(1c) methods show clinically significant interferences with samples containing HbE or HbD traits. To avoid reporting of inaccurate results, ion-exchange chromatograms must be carefully examined to identify possible interference from these Hb variants. For some methods, manufacturers' instructions do not provide adequate information for making correct decisions about reporting results.

  16. Stark broadening parameter tables for Ar VIII

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    Dimitrijević M.S.


    Full Text Available Using a semiclassical approach, we have calculated electron−, proton−, and He III−impact line widths and shifts for 9 Ar VIII transitions as a function of temperature and perturber density.

  17. Stark broadening parameter tables for Kr VIII

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    Dimitrijević M.S.


    Full Text Available Using a semiclassical approach, we have calculated electron−, proton−, and He III−impact line widths and shifts for 6 Kr VIII multiplets as a function of temperature and perturber density.

  18. Physicochemical characterisation of rVIII-SingleChain, a novel recombinant single-chain factor VIII. (United States)

    Schmidbauer, Stefan; Witzel, Reinhild; Robbel, Lars; Sebastian, Petra; Grammel, Nicolas; Metzner, Hubert J; Schulte, Stefan


    rVIII-SingleChain is a novel recombinant single-chain factor VIII (FVIII) construct, comprising covalently bonded heavy and light chains. Post-translational modifications of FVIII affect physicochemical parameters, including hydrophobicity and charge. The most relevant post-translational modifications of FVIII products are N-glycosylation of asparagine residues and tyrosine sulphations. Here, the physicochemical properties, thrombin cleavage products and post-translational modifications of rVIII-SingleChain were investigated and compared against commercially available recombinant FVIII (rFVIII) products with a predominant two-chain structure (B-domain deleted rFVIII and full-length rFVIII). rVIII-SingleChain was expressed in Chinese hamster ovary (CHO) cells and purified by chromatographic methods. Physicochemical properties of rVIII-SingleChain or thrombin-derived cleavage products were assessed using size-exclusion chromatography, reversed-phase chromatography and sodium dodecyl sulphate polyacrylamide gel electrophoresis. Analysis of the respective carbohydrate structures was performed after release of N-glycans by PNGase F followed by fluorescence labelling and high-performance liquid chromatography. Proteolysis by trypsin generated the corresponding peptides, which were analysed for sulphated tyrosines by liquid chromatography-electrospray ionisation time of flight-mass spectrometry. rVIII-SingleChain was shown to be of high purity and homogeneity, and presented a well-defined single-chain molecule with predominant β-sheet conformation. The coagulation-relevant thrombin-activation products of rVIII-SingleChain were comparable with those obtained by activation of commercially available rFVIII products. rVIII-SingleChain post-translational modifications were similar to other CHO cell-derived rFVIII products for N-glycopattern and tyrosine sulphation. In conclusion, rVIII-SingleChain is of high homogeneity and purity, and provides an expected cleavage pattern on

  19. Blood coagulation factor VIII: An overview

    Indian Academy of Sciences (India)

    Factor VIII (FVIII) functions as a co-factor in the blood coagulation cascade for the proteolytic activation of factor X by factor IXa. Deficiency of FVIII causes hemophilia A, the most commonly inherited bleeding disorder. This review highlights current knowledge on selected aspects of FVIII in which both the scientist and the ...

  20. Hemoglobin (Hb) Val de Marne (Hb Footscray) in Brazil: the first case report. (United States)

    Okumura, J V; Shimauti, E L T; Silva, D G H; Torres, L S; Belini-Junior, E; Oliveira, R G; Patussi, E V; Herrero, J C M; Bonini-Domingos, C R


    Hemoglobin (Hb) variants involving alpha-chains are less common in the global population than Hb variants resulting from beta-chain alterations. Generally, alpha-chain Hb variants are caused by point mutations affecting alpha-1 and/or alpha-2 genes of the alpha-globin cluster (HBA1 and HBA2). In Brazil, the most prevalent alpha-chain Hb variant is Hb Hasharon. In this study, we present the first case of an Hb Val de Marne variant in the Americas, specifically in Brazil.

  1. Biosynthesis and characterization of polyhydroxyalkanoate block copolymer P3HB-b-P4HB. (United States)

    Hu, Die; Chung, Ah-Leum; Wu, Lin-Ping; Zhang, Xin; Wu, Qiong; Chen, Jin-Chun; Chen, Guo-Qiang


    Polyhydroxyalkanoates (PHA) synthesis genes phbC and orfZ cloned from Ralstonia eutropha H16 were transformed into beta-oxidation weakened Pseudomonas putida KTOY08ΔGC, a mutant of P. putida KT2442. The recombinant P. putida strain termed KTHH06 was able to produce a short-chain-length PHA block copolymer consisting of poly(3-hydroxybutyrate) (P3HB) as one block and poly(4-hydroxybutyrate) (P4HB) as another block. One-dimensional and two-dimensional nuclear magnetic resonance (NMR) clearly indicated the polymer was a diblock copolymer consisting of 20 mol % P3HB as one block and 80 mol % P4HB as another one. Differential scanning calorimetric (DSC) showed that P3HB block melting temperatures (T(m)) in the block copolymer P3HB-b-P4HB was shift to low temperature compared with homopolymer P3HB and a blend of P3HB and P4HB. The block copolymer with a number average molecular weight of 50000 Da and a polydispersity of 3.1 demonstrated a better yield and tensile strength compared with that of its related random copolymer and blend of homopolymers of P3HB and P4HB.

  2. Heat transfer burnout of Mark VIII fuel

    Energy Technology Data Exchange (ETDEWEB)

    Bernath, L.


    The operating conditions to which the special Mark VIII quatrefoils will be exposed during the proposed piloting program have been compared with the conditions required to cause burnout, using an established method of calculating these conditions. The results of this comparison permit the following conclusions to be drawn: (1) With normal flow of coolant through the special elements the heat flux to be encountered in the R-8 cycle (1400 MW) will be 70% or that required to cause burnout (30% margin from burnout). (2) With a reduction of coolant flow to 82% of normal through one tube of a special element, burnout of that fuel column is possible in the R-8 cycle. (3) In the R-6 cycle (1280 MW), the margin from burnout in the special Mark VIII quatrefoils is 42% with full flow and 20% with the above reduced coolant flow. A similar comparison of operating conditions predicted for the L-3 cycle (full Mark VIII charge) shows that, even at the highest power level (1250 MW), the margin from burnout is greater than 55% with normal flow and 40% with reduced flow.

  3. Hb Melusine and Hb Athens-Georgia: potentially underreported in the Belgian population? Four cases demonstrating the lack of detection using common CE-HPLC methods either for glycated hemoglobin (HbA1C) analysis or Hb variant screening. (United States)

    Peeters, Bart; Brandt, Inger; Desmet, Koenraad; Harteveld, Cornelis L; Kieffer, Davy


    Suspected hemoglobin (Hb) variants, detected during HbA1C measurements should be further investigated, determining the extent of the interference with each method. This is the first report of Hb Melusine and Hb Athens-Georgia in Caucasian Belgian patients. Intervention & Technique: Since common CE-HPLC methods for HbA1C analysis or Hb variant screening are apparently unable to detect these Hb variants, their presence might be underestimated. HbA1C analysis using CZE, however, alerted for their presence. Moreover, in case of Hb Melusine, even Hb variant screening using CZE was unsuccessful in its detection. Fortunately, carriage of Hb Melusine or Hb Athens-Georgia variants has no clinical implications and, as shown in this report, no apparent difference in HbA1C should be expected.

  4. HbD Punjab/HbQ India compound heterozygosity: An unusual association.

    Directory of Open Access Journals (Sweden)

    Stacy Colaco


    Full Text Available Background: Haemoglobinopathies are the commonest hereditary disorders in India and pose a major health problem. Both beta thalassaemia and structural haemoglobin variants are relatively common in north western India. Here we report a 29 year old Sindhi female who was referred to us for a haemoglobinopathy work up and genetic counseling since her spouse was a classical beta thalassaemia carrier. Method: A complete blood count was done on an automated cell counter. Haemoglobin analysis was carried out using HPLC Variant Haemoglobin Testing System.  The cellulose acetate electrophoresis was carried out [pH 8.9]. Confirmation of mutations was done by automated DNA sequencing. Results: HPLC analysis showed four major peaks, HbA0, a peak in the HbD window, an unknown peak [retention time 4.74 minutes] and a peak in the HbC window. The HbA2 level was 2.2% and the HbF level was 0.7%.Cellulose acetate electrophoresis at alkaline pH, a slow moving band was seen at the HbS/D position along with a prominent band at the HbA2 position. DNA sequencing of the β and α genes showed presence of the 2 hemoglobin variants :Hb D [b 121GAA à CAA] and Hb Q [a 64 AAG à GAG]. The δ globin gene was normal. The additional peak in the HbC window was due to the formation of a heterodimer hybrid. Conclusion: Both HbD Punjab and HbQ India are relatively common in India but their co-inheritance has not been described in the country. This is the second report of compound heterozygosity for HbQ India/HbD Punjab haemoglobinopathy globally, and the first one from India.

  5. Hb variants in Korea: effect on HbA1c using five routine methods. (United States)

    Yun, Yeo-Min; Ji, Misuk; Ko, Dae-Hyun; Chun, Sail; Kwon, Gye Cheol; Lee, Kyunghoon; Song, Sang Hoon; Seong, Moon Woo; Park, Sung Sup; Song, Junghan


    Quantification of glycated hemoglobin (HbA1c) is a challenge in patients with hemoglobin (Hb) variants. We evaluated the impact of various Hb variants on five routine HbA1c assays by comparing with the IFCC reference measurement procedure (RMP). Whole blood samples showing warning flags or no results on routine HPLC HbA1c assays were confirmed for Hb variants and were submitted to HbA1c quantification using Sebia Capillarys 2 Flex Piercing, Roche Tina-quant HbA1c Gen. 2, Bio-Rad Variant II Turbo 2.0, ADAMS HA-8180, Tosoh G8 standard mode, and IFCC RMP using LC-MS. Among 114 samples, the most common variants were Hb G-Coushatta (n=47), Queens (n=41), Ube-4 (n=11), Chad (n=4), Yamagata (n=4), G-His-Tsou (n=2), G-Taipei (n=1), Fort de France (n=1), Hoshida (n=1), and two novel variants (Hb α-globin, HBA 52 Gly>Cys and Hb β-globin, HBB 146 His>Asn). In terms of control samples, all the result of HbA1c were "acceptable", within the criteria of ±7% compared to IFCC RMP target values. However, percentage of "unacceptable" results of samples with Hb variants were 16% for Capillarys 2, 7% for Tina-quant, 51% for Variant II Turbo 2.0, 95% for G8 standard mode, and 89% for HA-8180. The Capillarys 2 and HA-8180 assay did not provide the results in 5 and 40 samples with Hb variants, respectively. HbA1c results from five routine assays in patients with relatively common Hb variants in Korea showed various degrees of bias compared to those of IFCC RMP. Therefore, laboratories should be aware of the limitation of their methods with respect to interference from Hb variants found commonly in their local population and suggest an alternative HbA1c quantification method.

  6. Comparison of the characteristics of two hemoglobin variants, Hb D-Iran and Hb E, eluting in the Hb A2 window. (United States)

    Dass, Jasmita; Gupta, Aastha; Mittal, Suchi; Saraf, Amrita; Langer, Sabina; Bhargava, Manorama


    Cation exchange-high performance liquid chromatography (CE-HPLC) is most commonly used to evaluate hemoglobin (Hb) variants, which elute in the Hb A2 window. This study aimed to assess prevalence of an uncommon Hb variant, Hb D-Iran, and compare its red cell parameters and peak characteristics with those of Hb E that commonly elutes in the Hb A2 window. Generally, we assess abnormal Hb using CE-HPLC as the primary technique along with alkaline and acid electrophoresis. All cases with Hb A2 window >9%, as assessed by CE-HPLCs during 2009-2013, were selected. Twenty-nine cases with Hb D-Iran variant were identified-25 heterozygous, 2 homozygous, 1 compound heterozygous Hb D-Iran/β-thalassemia, and 1 Hb D-Iran/Hb D-Punjab. Overall prevalence of Hb D-Iran was 0.23%. Compared to patients with Hb E, those with Hb D-Iran had significantly higher Hb (12.1 vs. 11.3 g/dL, P=0.03), MCV (82.4 vs. 76.4 fL, P=0.0044), MCH (27.9 vs. 25.45 pg, P =0.0006), and MCHC (33.9 vs. 33.3 g/dL, P=0.0005). Amount of abnormal Hb (40.7 vs. 26.4%, P=0.0001) was significantly higher while retention time (3.56 vs. 3.70 min, P=0.0001) was significantly lower in Hb D-Iran than in Hb E. Hb D-Iran peak can be easily missed if area and retention time of the Hb A2 window are not carefully analyzed. To distinguish between variants, careful analysis of peak area and retention time is sufficient in most cases and may be further confirmed by the second technique-alkaline electrophoresis.

  7. HB+ inserted into the CMS Solenoid

    CERN Multimedia

    Tejinder S. Virdee, CERN


    The first half of the barrel hadron calorimeter (HB+) has been inserted into the superconducting solenoid of CMS, in preparation for the magnet test and cosmic challenge. The operation went smoothly, lasting a couple of days.

  8. Preparing for ENDF/B-VIII (United States)

    Brown, David


    Although the next major release of the ENDF/B library is not due until the 2017-2018 time frame, ENDF/B-VIII is already positioned to become the most important release of the library in some time. ENDF/B-VIII will be built around the Neutron Reaction Standards as well as the 1H, 16O, 56Fe, 235U, 238U and 239Pu evaluations developed as part of the Coordinated International Evaluation Library Organization (CIELO) pilot project. In this contribution, we summarize these improvements as well as the many other improvements to ENDF that have already been made or are scheduled to be made in the next year. Improvements already included in the ENDF/B-VIII beta releases: • Aggressive use of the flexible and physically correct LRF=7 resolved resonance format in 12 updated evaluations (35,37Cl, 40Ca, 54,56,57Fe, 63,65Cu and 182,183,184,186W) • Thermal capture gammas from the EGAF project (6,7Li, 11B, 19F, 23Na, 27Al, 28Si, 35,37Cl) • Thermal Scattering Law evaluations from NCSU (α and β phase SiO2, SiC, lucite, BeO, and polyethylene) and from the CAB-CNL collaboration (heavy and light water) • Many new evaluations in the neutron sublibrary (n, 12,13C, 40Ar, 54,57,58Fe, 58,59,60,61,62,64Ni, 63,65Cu, 73As, 120Sn, 236m1Np) Inclusion of Red Cullen's EPICS2014 library, updating the photo-atomic, electron and atomic-relaxation sublibraries. Many improvements are planned in the next year including new evaluations such as charged particle evaluations translated from LLNL's ECPL. In addition to these major changes, ENDF/B-VIII will be the first official library released simultaneously in the legacy ENDF-6 and the newly developed Generalized Nuclear Data (GND) formats.

  9. Acquired Factor VIII Inhibitors: Three Cases

    Directory of Open Access Journals (Sweden)

    Tay Za Kyaw


    Full Text Available Acquired hemophilia A is a rare, but devastating bleeding disorder caused by spontaneous development of autoantibodies directed against coagulation factor VIII. In 40%-50% of patients it is associated with such conditions as the postpartum period, malignancy, use of medications, and autoimmune diseases; however, its cause is unknown in most cases. Acquired hemophilia A should be suspected in patients that present with a coagulation abnormality, and a negative personal and family history of bleeding. Herein we report 3 patients with acquired hemophilia A that had different underlying pathologies, clinical presentations, and therapeutic responses. Factor VIII inhibitor formation in case 1 occurred 6 months after giving birth; underlying disorders were not identified in cases 2 or 3. The bleeding phenotype in these patients’ ranged from no bleeding tendency with isolated prolongation of APTT (activated partial thromboplastin time to severe intramuscular hematoma and hemarthrosis necessitating recombinant activated factor VII infusion and blood components transfusion. Variable responses to immunosuppressive treatment were also observed.

  10. 12 CFR 611.1137 - Title VIII service corporations. (United States)


    ... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Title VIII service corporations. 611.1137 Section 611.1137 Banks and Banking FARM CREDIT ADMINISTRATION FARM CREDIT SYSTEM ORGANIZATION Service... authorities granted under title VIII of the Act to act as an agricultural mortgage marketing facility. (b) How...

  11. The influence of prophylactic factor VIII in severe hemophilia A (United States)

    Gissel, Matthew; Whelihan, Matthew F; Ferris, Lauren A; Mann, Kenneth G; Rivard, Georges E; Brummel-Ziedins, Kathleen E


    Introduction Hemophilia A individuals displaying a similar genetic defect have heterogeneous clinical phenotypes. Aim To evaluate the underlying effect of exogenous factor (f)VIII on tissue factor (Tf)-initiated blood coagulation in severe hemophilia utilizing both empirical and computational models. Methods We investigated twenty-five clinically severe hemophilia A patients. All individuals were on fVIII prophylaxis and had not received fVIII from 0.25 to 4 days prior to phlebotomy. Coagulation was initiated by the addition of Tf to contact-pathway inhibited whole blood ± an anti-fVIII antibody. Aliquots were quenched over 20 min and analyzed for thrombin generation and fibrin formation. Coagulation factor levels were obtained and used to computationally predict thrombin generation with fVIII set to either zero or its value at the time of the draw. Results Due to prophylactic fVIII, at the time of the blood draw, the individuals had fVIII levels that ranged from hemophilia A. The combination of each individual's coagulation factors (outside of fVIII) determine each individual's baseline thrombin potential and may affect bleeding risk. PMID:21899664

  12. Radiative proton capture on He-6

    NARCIS (Netherlands)

    Sauvan, E.; Marqués, F.M.; Wilschut, H.W.; Orr, N.A.; Angelique, J.C.; Borcea, C.; Catford, W.N.; Clarke, N.M.; Descouvemont, P.; Diaz, J.; Grevy, S.; Kugler, A.; Kravchuk, V.; Labiche, M.; Le Brun, C.; Lienard, E.; Löhner, H.; Mittig, W.; Ostendorf, R.W.; Pietri, S.; Roussel-Chomaz, P.; Saint Laurent, M.G.; Savajols, H.; Wagner, V.; Yahlali, N.


    Radiative capture of protons is investigated as a probe of clustering in nuclei far from stability. The first such measurement on a halo nucleus is reported here for the reaction He-6(p, gamma) at 40 MeV. Capture into Li-7 is observed as the strongest channel. In addition, events have been recorded

  13. Polarization measurements of proton capture gamma rays

    NARCIS (Netherlands)

    Suffert, M.; Endt, P.M.; Hoogenboom, A.M.


    The linear polarization has been measured of eight different gamma rays of widely differing energies (Eγ = 0.8 - 8.0 MeV) emitted at resonances in the 24Mg(p, γ)25Al, 30Si(p, γ)31P, and 32S(p, γ)33Cl reactions. The gamma rays emitted at 90° to the proton beam were Compton scattered in a 2″ NaI

  14. A novel double heterozygous Hb Fontainebleau/HbD Punjab hemoglobinopathy. (United States)

    Rodríguez-Capote, Karina; Estey, Mathew P; Barakauskas, Vilte; Bordeleau, Pierre; Christensen, Cathie-Lou; Zuberbuhler, Peter; Higgins, Trefor N


    To report the finding of a novel double heterozygous hemoglobinopathy, the coinheritance of Hb Fontainebleau (α-chain variant) with HbD-Punjab (β-chain variant) discovered upon investigation of unexplained microcytosis in an infant. Hemoglobinopathy investigation was performed by high performance liquid chromatography (HPLC) using the β-thalassemia Short Program on the Bio-Rad Variant II(TM) followed by gel electrophoresis at alkaline and acid pH (Sebia Hydrasys 2 Electrophoresis System) and molecular diagnostic testing. This study complied with our institutional board ethics requirements. HPLC and electrophoresis suggested a complex α- and β-chain hemoglobinopathy with presumptive identification of the beta Hb variant as Hb D-Punjab. DNA sequencing analysis revealed the presence of a double heterozygous status for Hb Fontainebleau/Hb D-Punjab. In this paper we report the coinheritance of Hb Fontainebleau with Hb D-Punjab. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  15. Molecular characterization of HbEREBP2, a jasmonate- responsive ...

    African Journals Online (AJOL)



    Aug 29, 2011 ... HbEREBP2 expression. Effect of methyl jasmonate and ethephon on the expression of HbEREBP2. HbEREBP2 expression was rapidly and strongly up- regulated by methyl jasmonate, which was in contrast to the effect of tapping and mechanical wounding. The expression of HbEREBP2 was up-regulated ...

  16. HbA1c determination by HPLC: interference of hemoglobin variants HbS, HbC and HbF high concentration


    Maria das Graças Santos Menezes; Fábio David Couto; Lázaro Silveira Santos Junior; Elisângela Vitória Adôrno; Cynara Gomes Barbosa; Marilda de Souza Gonçalves; Ricardo David Couto


    INTRODUÇÃO: O diabetes mellitus (DM) é considerado um problema importante de saúde pública; possui prevalência elevada e nos últimos anos observa-se aumento progressivo na sua incidência. OBJETIVO: verificar possíveis variações na concentração de hemoglobina (Hb) glicada (HbA1c) na presença de Hbs S e C e avaliar o impacto da redução da HbA1c na avaliação clínica e no monitoramento do paciente diabético. MATERIAL E MÉTODOS: Foram incluídos no estudo, 150 indivíduos diabéticos oriundos da cida...

  17. Co-inheritance of α0 -thalassemia elevates Hb A2 level in homozygous Hb E: Diagnostic implications. (United States)

    Singha, K; Srivorakun, H; Fucharoen, G; Fucharoen, S


    Differentiation of homozygous hemoglobin (Hb) E with and without α0 -thalassemia is subtle on routine hematological ground. We examined in a large cohort of homozygous Hb E if the level of Hb A2 is helpful. A total of 592 subjects with homozygous Hb E were recruited from ongoing thalassemia screening program. Additionally, five couples at risk of having fetuses with Hb Bart's hydrops fetalis who were homozygous Hb E were also investigated. Hb analysis was performed using capillary electrophoresis system. Globin genotypes were defined by DNA analysis. Subjects were classified into four groups including pure homozygous Hb E (n=532), homozygous Hb E/α0 -thalassemia (n=48), Hb Constant Spring EE Bart's disease (n=8), and Hb EE Bart's disease (n=4). The levels of Hb A2 were found, respectively, to be 4.97±0.69, 6.64±1.02, 4.86±0.87, and 7.60±1.04%. Among five couples at risk, α0 -thalassemia was identified in three subjects with Hb A2 >6.0%. Increased Hb A2 level is a useful marker for differentiation of homozygous Hb E with and without α0 -thalassemia. This should lead to a significant reduction in number of referral cases of homozygous Hb E for molecular testing of α0 -thalassemia in routine practice. © 2017 John Wiley & Sons Ltd.

  18. Bilateral Renal Vein Thrombosis due to Elevated Factor VIII Levels. (United States)

    Patole, Shalom; Ramya, I


    Recent evidence has shown that high level of factor VIII is associated with increased risk of thromboembolism. High factor VIII levels are associated with a seven-fold increase in the risk of venous thrombosis. Renal vein thrombosis is usually associated with nephrotic syndrome, procoagulant state or oral contraceptive pills. We report a case of a lady who presented with bilateral renal vein thrombosis due to high factor VIII levels and oral contraceptive pills (OCP) use. © Journal of the Association of Physicians of India 2011.

  19. Factoring in Factor VIII With Acute Ischemic Stroke. (United States)

    Siegler, James E; Samai, Alyana; Albright, Karen C; Boehme, Amelia K; Martin-Schild, Sheryl


    There is growing research interest into the etiologies of cryptogenic stroke, in particular as it relates to hypercoagulable states. An elevation in serum levels of the procoagulant factor VIII is recognized as one such culprit of occult cerebral infarctions. It is the objective of the present review to summarize the molecular role of factor VIII in thrombogenesis and its clinical use in the diagnosis and prognosis of acute ischemic stroke. We also discuss the utility of screening for serum factor VIII levels among patients at risk for, or those who have experienced, ischemic stroke. © The Author(s) 2015.

  20. Detection of Co-inheritance of Hb Hope and Hb Constant Spring in Three Thai Samples by Capillary Electrophoresis. (United States)

    Panyasai, Sitthichai; Pornprasert, Sakorn


    The diagnosis of co-inheritance of Hb Hope [β136(H14)Gly → Asp, GGT > GAT] and Hb constant spring [Hb CS; α142, Term → Gln (TAA > CAA IN α2)] by high performance liquid chromatography (HPLC) is difficult because Hb Hope has a HPLC elution pattern similar to that of Hb Pyrgos, Hb New York, Hb Kodaira, and Hb Phimai. Moreover, the Hb CS mRNA, as well as the gene product, are unstable and present at a low level in peripheral blood. We report the use of a capillary electrophoresis (CE) for diagnosis of co-inheritance of Hb Hope and Hb CS in 3 Thai females who had mild anemia with Hb and Hct varying from 91-114 g/L to 0.28-0.36 L/L, respectively. Hb Hope eluted with a retention time of 125-140 s (Zone 10) of CE electrophoregram. Furthermore, the peak of Hb CS at the retention time of 245-250 s (Zone 2) was observed in these samples. In addition, the manual analysis by taking the non-black area under both peaks of HbA and Hb Hope (inverted V) into account provided the corrected Hb CS levels which are useful in screening of heterozygote or homozygote for Hb CS. Thus, the CE method provides an accurate diagnosis of Hb Hope and Hb CS which is useful in genetic counseling, prevention and control programs for these hemoglobinopathies.

  1. A Novel Double Heterozygous Hb D-Punjab/Hb J-Meerut Hemoglobinopathy. (United States)

    Chandra, Dinesh; Tyagi, Seema; Deka, Roopam; Chauhan, Richa; Seth, Tulika; Saxena, Renu; Pati, H P


    A comprehensive laboratory diagnosis of hemoglobinopathies forms an integral part in workup of disorders of globin chain synthesis. Clinical findings, complete blood counts, peripheral smear examination along with hemoglobin (Hb) electrophoresis and/or cation exchange high performance liquid chromatography findings and parental study helps to clinch a final diagnosis. Compound heterozygous hemoglobinopathy presents with variable clinical findings and some of them are picked up on screening tests done as part of routine antenatal workup. Here we report a rare double heterozygous hemoglobinopathy of Hb D-Punjab and Hb J-Meerut in a 35 year antenatal female.

  2. Identification of Hb Wayne and its effects on HbA1c measurement by 5 methods. (United States)

    Rodríguez-Capote, Karina; Estey, Mathew P; Barakauskas, Vilte E; Burton, Teralee; Holmes, Deborah; Krause, Richard; Higgins, Trefor N


    The World Health Organization and the American and Canadian Diabetes Associations approved HbA1c >6.5% as diagnostic for type 2 diabetes mellitus (T2DM). Hb variants and/or their chemically modified species can interfere with HbA1c measurements. We recently described a patient with Hb Wayne trait who was misdiagnosed with T2DM based on falsely elevated HbA1c. Hb Wayne is a clinically silent variant that exists as two isoforms: Hb Wayne I (Asn 139) and Hb Wayne II (Asp 139). Hemoglobinopathy investigation was performed by HPLC (Bio-Rad VARIANT-II), alkaline and acid electrophoresis (Sebia Hydrasis2), capillary zone electrophoresis (Sebia CAPILLARYS2™) and DNA sequencing. HbA1c was measured by five methods. Hb Wayne eluted as two small fractions with retention times of 1.0 and 1.46min on the HPLC (Bio-Rad VARIANT-II). Alkaline gel and capillary electrophoresis showed two small bands migrating faster than HbA. Hb Wayne generated spuriously high results on the Bio-Rad VARIANT-II Turbo 2.0, no results on the Tosoh G8, and did not interfere with either the Sebia CAPILLARYS2™ or immunoassays from Roche (tinaquant) and Siemens (Bayer DCA2000+). Based on the Hb Wayne HPLC profile of 3 patients, an algorithm was developed to facilitate its detection, which identified 9 additional patients with Hb Wayne trait. We characterize Hb Wayne by chromatographic and electrophoretic techniques and show the effect of Hb Wayne on five common HbA1c methodologies. We developed a quality assurance tool to assist in detecting Hb Wayne trait during HbA1c analysis on the Bio-Rad VARIANT-II™ Turbo 2.0. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  3. Stark broadening parameter tables for K VIII and K IX

    Directory of Open Access Journals (Sweden)

    Dimitrijević M.S.


    Full Text Available Using a semiclassical approach, we have calculated electron−, proton−, and He III−impact line widths and shifts for 4 K VIII and 30 K IX multiplets as a function of temperature and perturber density.

  4. Abnormal cerebellar development and ataxia in CARP VIII morphant zebrafish. (United States)

    Aspatwar, Ashok; Tolvanen, Martti E E; Jokitalo, Eija; Parikka, Mataleena; Ortutay, Csaba; Harjula, Sanna-Kaisa E; Rämet, Mika; Vihinen, Mauno; Parkkila, Seppo


    Congenital ataxia and mental retardation are mainly caused by variations in the genes that affect brain development. Recent reports have shown that mutations in the CA8 gene are associated with mental retardation and ataxia in humans and ataxia in mice. The gene product, carbonic anhydrase-related protein VIII (CARP VIII), is predominantly present in cerebellar Purkinje cells, where it interacts with the inositol 1,4,5-trisphosphate receptor type 1, a calcium channel. In this study, we investigated the effects of the loss of function of CARP VIII during embryonic development in zebrafish using antisense morpholino oligonucleotides against the CA8 gene. Knockdown of CA8 in zebrafish larvae resulted in a curved body axis, pericardial edema and abnormal movement patterns. Histologic examination revealed gross morphologic defects in the cerebellar region and in the muscle. Electron microscopy studies showed increased neuronal cell death in developing larvae injected with CA8 antisense morpholinos. These data suggest a pivotal role for CARP VIII during embryonic development. Furthermore, suppression of CA8 expression leads to defects in motor and coordination functions, mimicking the ataxic human phenotype. This work reveals an evolutionarily conserved function of CARP VIII in brain development and introduces a novel zebrafish model in which to investigate the mechanisms of CARP VIII-related ataxia and mental retardation in humans.

  5. Factor VIII/V C-domain swaps reveal discrete C-domain roles in factor VIII function and intracellular trafficking


    Ebberink, Eduard H T M; Bouwens, Eveline A. M.; Bloem, Esther; Boon-Spijker, Mariëtte; van den Biggelaar, Maartje; Voorberg, Jan; Alexander B. Meijer; Mertens, Koen


    Factor VIII C-domains are believed to have specific functions in cofactor activity and in interactions with von Willebrand factor. We have previously shown that factor VIII is co-targeted with von Willebrand factor to the Weibel-Palade bodies in blood outgrowth endothelial cells, even when factor VIII carries mutations in the light chain that are associated with defective von Willebrand factor binding. In this study, we addressed the contribution of individual factor VIII C-domains in intrace...

  6. Relationship between Hb and HbA1c in Japanese adults: an analysis of the 2009 Japan Society of Ningen Dock database. (United States)

    Takahashi, Eiko; Moriyama, Kengo; Yamakado, Minoru


    We investigated the effect of Hb on HbA1c levels in 265,427 Japanese individuals. The divergence between fasting plasma glucose (FPG) and HbA1c levels increased with lower Hb, resulting in HbA1c levels that were higher in relation to than the FPG levels. Similarly, the correlation between FPG and HbA1c levels, stratified by Hb, weakened as Hb decreased. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  7. Characterization of HbWRKY1, a WRKY transcription factor from Hevea brasiliensis that negatively regulates HbSRPP. (United States)

    Wang, Ying; Guo, Dong; Li, Hui-Liang; Peng, Shi-Qing


    Small rubber particle protein (SRPP) is a major component of Hevea brasiliensis (H. brasiliensis) latex, which is involved in natural rubber (NR) biosynthesis. However, little information is available on the regulation of SRPP gene (HbSRPP) expression. To study the transcriptional regulation of HbSRPP, the yeast one-hybrid experiment was performed to screen the latex cDNA library using the HbSRPP promoter as bait. One cDNA that encodes the WRKY transcription factor, designated as HbWRKY1, was isolated from H. brasiliensis. HbWRKY1 contains a 1437 bp open reading frame that encodes 478 amino acids. The deduced HbWRKY1 protein was predicted to possess two conserved WRKY domains and a C2H2 zinc-finger motif. HbWRKY1 was expressed at different levels, with the highest transcription in the flower, followed by the bark, latex, and leaf. Furthermore, the co-expression of pHbSRP::GUS with CaMV35S::HbWRKY1 significantly decreased the GUS activity in transgenic tobacco, indicating that HbWRKY1 significantly suppressed the HbSRPP promoter. These results suggested that HbWRKY1 maybe a negative transcription regulator of HbSRPP involved in NR biosynthesis in H. brasiliensis. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  8. AAV5-Factor VIII Gene Transfer in Severe Hemophilia A. (United States)

    Rangarajan, Savita; Walsh, Liron; Lester, Will; Perry, David; Madan, Bella; Laffan, Michael; Yu, Hua; Vettermann, Christian; Pierce, Glenn F; Wong, Wing Y; Pasi, K John


    Patients with hemophilia A rely on exogenous factor VIII to prevent bleeding in joints, soft tissue, and the central nervous system. Although successful gene transfer has been reported in patients with hemophilia B, the large size of the factor VIII coding region has precluded improved outcomes with gene therapy in patients with hemophilia A. We infused a single intravenous dose of a codon-optimized adeno-associated virus serotype 5 (AAV5) vector encoding a B-domain-deleted human factor VIII (AAV5-hFVIII-SQ) in nine men with severe hemophilia A. Participants were enrolled sequentially into one of three dose cohorts (low dose [one participant], intermediate dose [one participant], and high dose [seven participants]) and were followed through 52 weeks. Factor VIII activity levels remained at 3 IU or less per deciliter in the recipients of the low or intermediate dose. In the high-dose cohort, the factor VIII activity level was more than 5 IU per deciliter between weeks 2 and 9 after gene transfer in all seven participants, and the level in six participants increased to a normal value (>50 IU per deciliter) that was maintained at 1 year after receipt of the dose. In the high-dose cohort, the median annualized bleeding rate among participants who had previously received prophylactic therapy decreased from 16 events before the study to 1 event after gene transfer, and factor VIII use for participant-reported bleeding ceased in all the participants in this cohort by week 22. The primary adverse event was an elevation in the serum alanine aminotransferase level to 1.5 times the upper limit of the normal range or less. Progression of preexisting chronic arthropathy in one participant was the only serious adverse event. No neutralizing antibodies to factor VIII were detected. The infusion of AAV5-hFVIII-SQ was associated with the sustained normalization of factor VIII activity level over a period of 1 year in six of seven participants who received a high dose, with

  9. Idiopathic Acquired Hemophilia A with Undetectable Factor VIII Inhibitor

    Directory of Open Access Journals (Sweden)

    Nicholas B. Abt


    Full Text Available Objective. We present the case of a 73-year-old female, with no family or personal history of a bleeding disorder, who had a classic presentation for acquired hemophilia A. Factor VIII activity was low but detectable and a factor VIII inhibitor was undetectable. Methods. The patient’s plasma was comprehensively studied to determine the cause of the acquired coagulopathy. Using the Nijmegen modification of the Bethesda assay, no factor VIII autoantibody was measureable despite varying the incubation time from 1 to 3 hours. Results. The aPTT was prolonged at 46.8 seconds, which did not correct in the 4 : 1 mix but did with 1 : 1 mix. Using a one stage factor VIII activity assay, the FVIII activity was 16% and chromogenic FVIII activity was also 16%. The patient was treated with recombinant FVII and transfusion, significantly reducing bleeding. Long-term therapy was initiated with cyclophosphamide and prednisone with normalization of FVIII activity. Conclusions. Physicians can be presented with the challenging clinical picture of an acquired factor VIII inhibitor without a detectable inhibitor by the Bethesda assay. Standard therapy for an acquired hemophilia A should be considered.

  10. Igor Zabel 14. VIII 1958 - 23. VII 2005

    Index Scriptorium Estoniae


    Igor Zabel oli Ida-Euroopa tuntumaid kunstiteoreetikuid ja kuraatoreid. Töötas 1986. aastast Ljubljana moodsa kunsti muuseumi kuraatorina. 9. VIII avatakse seal viimane I. Zabeli kureeritud näitus "Territories, Identities, Nets-Slovene Art 1995-2005"

  11. What history tells us VIII. The progressive construction of a ...

    Indian Academy of Sciences (India)


    Feb 9, 2007 ... Home; Journals; Journal of Biosciences; Volume 32; Issue 2. What history tells us VIII. The progressive construction of a mechanism for prion diseases. Michel Morange. Series Volume 32 Issue 2 March 2007 pp 223-227. Fulltext. Click here to view fulltext PDF. Permanent link:

  12. The labour ward analgesic service at King Edward VIII Hospital ...

    African Journals Online (AJOL)

    dence of shivering9 and an improved sense of maternal well-being.lo. In summary, the study presented here shows that the analgesia service provided ro the labour ward at King. Edward VIII Hospital is at present grossly inadequate. In particular, a high proportion (76%) of mothers with a specific indication for epidural ...

  13. Functional regions in coagulation factor VIII explored by mass spectrometry

    NARCIS (Netherlands)

    Bloem, E.


    The molecular mechanisms behind the function of factor VIII (FVIII) have remained poorly understood. FVIII acts in the blood coagulation cascade as cofactor for activated factor IX (FIXa) in the membrane bound activated factor X generating (FXase) complex. A functional absence in FVIII leads to the

  14. Drugs affecting HbA1c levels

    Directory of Open Access Journals (Sweden)

    Ranjit Unnikrishnan


    Full Text Available Glycated hemoglobin (HbA1c is an important indicator of glycemic control in diabetes mellitus, based on which important diagnostic and therapeutic decisions are routinely made. However, there are several situations in which the level of HbA1c may not faithfully reflect the glycemic control in a given patient. Important among these is the use of certain non-diabetic medications, which can affect the HbA1c levels in different ways. This review focuses on the non-diabetic medications which can inappropriately raise or lower the HbA1c levels, and the postulated mechanisms for the same.

  15. Comparison of factor VIII transgenes bioengineered for improved expression in gene therapy of hemophilia A. (United States)

    Dooriss, Kerry L; Denning, Gabriela; Gangadharan, Bagirath; Javazon, Elisabeth H; McCarty, David A; Spencer, H Trent; Doering, Christopher B


    Successful gene therapy of hemophilia A depends on the sustained expression of therapeutic levels of factor VIII (fVIII). Because of mRNA instability, interactions with resident endoplasmic reticulum (ER) chaperones, and the requirement for carbohydrate-facilitated transport from the ER to the Golgi apparatus, fVIII is expressed at much lower levels from mammalian cells than other proteins of similar size and complexity. A number of bioengineered forms of B domain-deleted (BDD) human fVIII have been generated and shown to have enhanced expression. Previously, we demonstrated that recombinant BDD porcine fVIII exhibits high-level expression due to specific sequence elements that increase biosynthesis via enhanced posttranslational transit through the secretory pathway. In the current study, high-expression recombinant fVIII constructs were compared directly in order to determine the relative expression of the various bioengineered fVIII transgenes. The data demonstrate that BDD porcine fVIII expression is superior to that of any of the human fVIII variant constructs tested. Mean fVIII expression of 18 units/10(6) cells/24 hr was observed from HEK-293 cells expressing a single copy of the porcine fVIII transgene, which was 36- to 225-fold greater than that of any human fVIII transgene tested. Furthermore, greater than 10-fold higher expression was observed in human cells transduced with BDD porcine fVIII versus BDD human fVIII-encoding lentiviral vectors, even at low proviral copy numbers, supporting its use over other human fVIII variants in future hemophilia A gene therapy clinical trials.

  16. Dietary determinants for Hb-acrylamide and Hb-glycidamide adducts in Danish non-smoking women

    DEFF Research Database (Denmark)

    Outzen, Malene; Egeberg, Rikke; Dragsted, Lars


    in Hb-AA. Intakes of coffee and biscuits/crackers were statistically significantly associated with a 3 % per 200 g/d (95 % CI 1, 6; P = 0·005) and 12 % per 10 g/d (95 % CI 3, 23; P = 0·01) higher Hb-GA, respectively. This model explained 12 % of the variation in Hb-GA. In conclusion, only a few dietary...

  17. Phenotypic Diversity of Sickle Cell Disease in Patients with a Double Heterozygosity for Hb S and Hb D-Punjab. (United States)

    Torres, Lidiane S; Okumura, Jéssika V; Belini-Júnior, Édis; Oliveira, Renan G; Nascimento, Patrícia P; Silva, Danilo G H; Lobo, Clarisse L C; Oliani, Sonia M; Bonini-Domingos, Claudia R


    Phenotypic heterogeneity for sickle cell disease is associated to several genetic factors such as genotype for sickle cell disease, β-globin gene cluster haplotypes and Hb F levels. The coinheritance of Hb S (HBB: c.20A > T) and Hb D-Punjab (HBB: c.364G > C) results in a double heterozygosity, which constitutes one of the genotypic causes of sickle cell disease. This study aimed to assess the phenotypic diversity of sickle cell disease presented by carriers of the Hb S/Hb D-Punjab genotype and the Bantu [- + - - - -] haplotype. We evaluated medical records from 12 patients with sickle cell disease whose Hb S/Hb D-Punjab genotype and Bantu haplotype were confirmed by molecular analysis. Hb S and Hb D-Punjab levels were quantified by chromatographic analysis. Mean concentrations of Hb S and Hb D-Punjab were 44.8 ± 2.3% and 43.3 ± 1.8%, respectively. Painful crises were present in eight (66.7%) patients evaluated, representing the most common clinical event. Acute chest syndrome (ACS) was the second most prevalent manifestation, occurring in two individuals (16.7%). Three patients were asymptomatic, while another two exhibited greater diversity of severe clinical manifestations. Medical records here analyzed reported a significant clinical diversity in sickle cell disease ranging from the absence of symptoms to wide phenotypic variety. The sickle cell disease genotype, Bantu haplotype and hemoglobin (Hb) levels did not influence the clinical diversity. Thus, we concluded that the phenotypic variation in sickle cell disease was present within a specific genotype for disease regardless of the β-globin gene cluster haplotypes.

  18. First Case of a Compound Heterozygosity for Two Nondeletional α-Thalassemia mutations, Hb Constant Spring and Hb Quong Sze. (United States)

    Zhou, Jian-Ying; Yan, Jin-Mei; Li, Jian; Li, Dong-Zhi


    Nondeletional α-thalassemia (α-thal) is the result of point mutations in critical regions of the α-globin genes, affecting mRNA processing, mRNA translation, or α-globin stability. Hb Constant Spring (Hb CS, HBA2: c.427T > C) is the most common nondeletional α-thal that results from a nucleotide substitution at the termination codon of the α2-globin gene. Hb Quong Sze (Hb QS, HBA2: c.377T > C) is another nondeletional α-thal in South China with the missense mutation at codon 125 of the α2-globin gene making this hemoglobin (Hb) variant highly unstable. Although homozygosity for Hb CS (α(CS)α/α(CS)α) or Hb QS (α(QS)α/α(QS)α) has been reported, clinical pictures vary from severe hemolysis that developed early in life to only mild anemia, no clinical phenotypic data of compound heterozygosity for Hb CS/Hb QS (α(CS)α/α(QS)α) has been described. In this report we describe an adult case with such a compound heterozygosity who presented with a mild α-thal.

  19. Characterization of Hb Lepore variants in the UK population. (United States)

    Guo, Lina; Kausar, Anika; Old, John M; Henderson, Shirley J; Gallienne, Alice E


    A molecular study of Hb Lepore heterozygotes identified by the UK population screening program has revealed four out of the five known Lepore variants. The region of homologous δ- and β-globin gene sequence was determined in 58 unrelated Hb Lepore heterozygotes referred for confirmation of their carrier status by DNA analysis through the national thalassemia and sickle cell screening program over a period of 10 years. The most common variant found was Hb Lepore-Boston-Washington (Hb LBW, HBD: c.265 C > c.315 + 7 C) observed in 46 carriers (79.0%). Hb Lepore-Hollandia (HBD: c.69 A > c.92 + 16 A) was found in nine cases (16.0%); Hb Lepore-Baltimore (HBD: c.208 G > c.254 C) in two cases (4.0%) and Hb Lepore-ARUP (HBD: c.97 C > c.150 C) in one carrier (2.0%). Analysis of the hematological findings showed no significant differences between the four groups. The wide range of Hb Lepore variants observed in this study confirms the very diverse range of α- and β-globin gene mutations observed in the UK population by previous studies.

  20. The optical emission from the supernova remnant HB 3 (United States)

    Fesen, R. A.; Gull, T. R.


    The supernova remnant HB 3 was first detected as a radio source by Brown and Hazard (1953). On the basis of subsequent radio studies, it was concluded that the object was a supernova remnant (SNR). HB 3 is located at the far western edge of the H II region/molecular cloud complex W3-W4-W5 (IC 1795-1805-1848). However, a physical association of HB 3 with this complex is uncertain. In the present investigation, attention is called to the probability that HB 3 exhibits a more extensive optical emission structure than previously realized, and one which agrees well with both the position and morphology of the radio emission. It is found that narrow-passband optical images strongly suggest an almost complete optical emission shell for HB 3. Spectroscopic observations are, however, required to confirm that this emission is characteristic of a SNR.

  1. First Report of a Chinese Family Carrying a Double Heterozygosity for Hb Q-Thailand and Hb J-Bangkok. (United States)

    Jiang, Fan; Zhou, Jian-Ying; Yan, Jin-Mei; Lu, Yue-Cheng; Li, Dong-Zhi


    The double heterozygosity for α and β chain variants leads to the formation of abnormal heterodimer hybrids, which could render laboratory diagnostics in a routine setting difficult. The following is the first report of a double heterozygosity for Hb Q-Thailand [α74(EF3)Asp→His; HBA1: c.223G>C] with α(+)-thalassemia (α(+)-thal) and Hb J-Bangkok [β56(D7)Gly→Asp; HBB: c.170G>A] found in a Chinese family. Both subjects were healthy with normal or borderline hematological parameters. Hemoglobin (Hb) analyses showed a novel variant, Hb Q-Thailand and Hb J-Bangkok. Family studies helped in the initial recognition and in making presumptive diagnoses, but definitive diagnoses of these cases with complex α and β chain variants could only be obtained after DNA analysis.

  2. TT virus contaminates first-generation recombinant factor VIII concentrates. (United States)

    Azzi, A; De Santis, R; Morfini, M; Zakrzewska, K; Musso, R; Santagostino, E; Castaman, G


    Recombinant factor VIII and factor IX concentrates, human-plasma-derived albumin, and samples from previously untreated patients with hemophilia were examined for the presence of TT virus (TTV) by using polymerase chain reaction testing. Blood samples from the patients were obtained prospectively before and every 3 to 6 months after therapy was begun. TTV was detected in 23.5% of the recombinant-product lots and 55.5% of the albumin lots tested. Only first-generation factor VIII recombinant concentrates stabilized with human albumin were positive for TTV, whereas all second-generation (human protein-free) concentrates were negative for the virus. In 59% of patients treated with either first- or second-generation recombinant factor concentrates, TTV infection developed at some point after the initial infusion. Infection with TTV in these patients before and after treatment did not appear to be clinically important. Thus, first-generation recombinant factor VIII concentrates may contain TTV and the source of the viral contamination may be human albumin.

  3. Incidental detection of haemoglobin (Hb) variants during high performance liquid chromatography (HPLC) analysis of HbA1c: is it time for a standardised approach to reporting? (United States)

    Reeve, J; Blake, L; Griffin, D; O'Shea, P


    Haemoglobin (Hb) variants are genetic variations in the globin genes that code for an abnormal globin protein structure. The prevalence of Hb variants has increased in Ireland due to the number of emigrants from Africa and Southeast Asia. The rate of incidentally detected Hb variants, in laboratories employing HPLC to measure HbA1c, has increased in parallel. The presence of a Hb variant can compromise HbA1c measurement and interpretation. In such cases, HbA1c cannot be used to diagnose diabetes or to assess concordance with glycaemic targets. To establish the number of incidentally identified Hb variants during 10 months of routine HbA1c analysis, and the percentage of HbA1c reports alerting the requesting clinician to the presence of a Hb variant. The laboratory database was interrogated to extract all records of HbA1c requests and incidentally identified Hb variants from March to December 2012. A total of 32,636 HbA1c analyses were performed during the evaluation period. Seventy-three Hb variants were identified in a total of 46 patients. In 32.6% (15 of 46) the haemoglobinopathy status was known prior to testing and 97% of HbA1c reports communicated the presence of the Hb variant to the requesting clinician. Hb variants may invalidate the results of HbA1c analysis and could result in a missed diagnosis or a misdiagnosis of diabetes or mismanagement of a patient with diabetes mellitus. It is, therefore, imperative that a comment alerting the requesting clinician to the presence of the Hb variant is appended to the HbA1c result.

  4. Iron deficiency anemia interfering the diagnosis of compound heterozygosity for Hb constant spring and Hb Paksé: The first case report. (United States)

    Chiasakul, Thita; Uaprasert, Noppacharn


    Diagnosis of thalassemia or hemoglobinopathy concomitant with iron deficiency anemia (IDA) is challenging. We report a case of 43-year-old female whose diagnosis of compound heterozygosity for hemoglobin Constant Spring (HbCS) and Hb Paksé became apparent after the treatment of IDA. Prior to treatment, Hb analysis using isoelectric focusing (IEF) showed HbA 95.6%, HbA2 2.7%, and HbCS 1.7% compatible with heterozygous HbCS. After 4 months of oral iron therapy resulting in an improved Hb level, her HbCS level was substantially increased to 8.7% on IEF suggesting homozygous HbCS. Subsequent DNA analysis using multiplex amplification refractory mutation system analysis revealed compound heterozygosity for HbCS and Hb Paksé. This case demonstrated that IDA can significantly reduce HbCS/Hb Paksé levels and probably mask the diagnosis of homozygous HbCS, homozygous Hb Paksé or the compound heterozygosity for both hemoglobinopathies by hemoblogin analysis. The test should be repeated after resolution of IDA, or molecular testing should be performed to confirm the diagnosis. © 2017 Wiley Periodicals, Inc.

  5. Differential proteolytic activation of factor VIII-von Willebrand factor complex by thrombin

    Energy Technology Data Exchange (ETDEWEB)

    Hill-Eubanks, D.C.; Parker, C.G.; Lollar, P. (Univ. of Vermont, Burlington (USA))


    Blood coagulation factor VIII (fVIII) is a plasma protein that is decreased or absent in hemophilia A. It is isolated as a mixture of heterodimers that contain a variably sized heavy chain and a common light chain. Thrombin catalyzes the activation of fVIII in a reaction that is associated with cleavages in both types of chain. The authors isolated a serine protease from Bothrops jararacussu snake venom that catalyzes thrombin-like heavy-chain cleavage but not light-chain cleavage in porcine fVIII as judged by NaDodSO{sub 4}/PAGE and N-terminal sequence analysis. Using a plasma-free assay of the ability of activated {sup 125}I-fVIII to function as a cofactor in the activation of factor X by factor IXa, they found that fVIII is activated by the venom enzyme. The venom enzyme-activated fVIII was isolated in stable form by cation-exchange HPLC. von Willebrand factor inhibited venom enzyme-activated fVIII but not thrombin-activated fVIII. These results suggest that the binding of fVIII to von Willebrand factor depends on the presence of an intact light chain and that activated fVIII must dissociate from von Willebrand factor to exert its cofactor effect. Thus, proteolytic activation of fVIII-von Willebrand factor complex appears to be differentially regulated by light-chain cleavage to dissociate the complex and heavy-chain cleavage to activate the cofactor function.

  6. 40 CFR Appendix Viii to Part 600 - Fuel Economy Label Formats (United States)


    ... 40 Protection of Environment 29 2010-07-01 2010-07-01 false Fuel Economy Label Formats VIII... POLICY FUEL ECONOMY AND CARBON-RELATED EXHAUST EMISSIONS OF MOTOR VEHICLES Pt. 600, App. VIII Appendix VIII to Part 600—Fuel Economy Label Formats EC01MY92.117 EC01MY92.118 EC01MY92.119 EC01MY92.120...

  7. Localization of collagen type VIII in normal and pathological human cornea


    Zenklová, Kateřina


    The aim of this work was to localize collagen type VIII in different layers of the cornea and to compare it's localization in normal corneas with pathological corneas obtained from patients with Fuchs endothelial dystrophy, posterior polymorphous dystrophy or keratoconus.The only comercially available antibody did not proove sufficient specifiky for collagen type VIII. With use of the antibody 9H3 anti alCVIII was collagen VIII evidenced in the cornea. This antibody can be used for detection ...

  8. Comparative haematological parameters of HbAA and HbAS genotype children infected with Plasmodium falciparum malaria in Yemen. (United States)

    Albiti, Anisa H; Nsiah, Kwabena


    Sickle haemoglobin (HbS) is known to offer considerable protection against falciparum malaria. However, the mechanism of protection is not yet completely understood. In this study, we investigate how the presence of the sickle cell trait affects the haematological profile of AS persons with malaria, in comparison with similarly infected persons with HbAA. This study is based on the hypothesis that the sickle cell trait plays a protective role against malaria. Children from an endemic malaria transmission area in Yemen were enrolled in this study. Hematological parameters were estimated using manual methods, the percentage of parasite density on stained thin smear was calculated, haemoglobin genotypes were determined on paper electrophoresis, ferritin was measured using enzyme-linked immunosorbent assay, serum iron and TIBC were assayed using spectrophotometer, transferrin saturation index was calculated by dividing serum iron by TIBC and expressing the result as a percentage. Haematological parameters were compared in HbAA- and HbAS-infected children. Falciparum malaria parasitaemia was confirmed in the blood smears of 62 children, 44 (55.7%) of AA and 18 (37.5%) AS, so there was higher prevalence in HbAA children (P = 0.047). Parasite density was lower in HbAS- than HbAA-infected children (P = 0.003). Anaemia was prominent in malaria-infected children, with high proportions of moderate and severe forms in HbAA (P = 0.001). The mean levels of haemoglobin, packed cell volume, reticulocyte count, platelets count, lymphocytes, eosinophils, and serum iron were significantly lower while total leukocytes, immature granulocytes, monocytes, erythrocyte sedimentation rate, transferrin saturation, and serum ferritin were significantly higher in HbAA-infected children than HbAS-infected children. Infection with Plasmodium falciparum malaria caused more significant haematological alterations of HbAA children than HbAS. This study supports the observation that sickle cell trait

  9. Factors regulating Hb F synthesis in thalassemic diseases

    Directory of Open Access Journals (Sweden)

    Lerone Maria


    Full Text Available Abstract Background The thalassemic syndromes originate from mutations of the globin genes that cause, besides the characteristic clinical picture, also an increased Hb F amount. It is not yet clear if there are more factors, besides the beta globin genotype, determining the Hb F production. We have tried to find out if there are relations between total Hb and Hb F, between erythropoietin (Epo and Hb F, between Hb F and point mutations of the gamma gene promoters. Materials and Methods Hematologic parameters, iron status, alpha/non-alpha globin ratio, Epo level, and thalassemic defects of the alpha-, beta-, and gamma-globin genes were explored using standard methods in patients affected by thalassemic diseases. Ninety-five non thalassemic individuals have been examined as controls. Results Two clinical variants of beta-thalassemia intermedia referred to as beta-thal int sub-silent and evident are associated with distinct sets of mutations of the beta-globin gene. Silent beta thal mutations are invariably associated with sub-silent beta thal int; beta° or severe beta+ thal mutations are associated with evident beta thal int (88% and almost invariably (98% with thalassemia major. A positive correlation was observed between the severity of the disease and the Hb F level, but no correlation was found between the Hb F and erythropoietin (Epo level. The mutation Ggamma -158 C→T was detected in 26.9% of patients affected by beta-thal int sub-silent and evident, respectively, but only in 2% of patients with thalassemia major. Conclusions The severity of beta-thal int and the increased Hb F level are strictly dependent from the type of beta-globin gene mutations. No relation is found between Hb F synthesis and Epo secretion. The mutation Ggamma -158 C→T, common among patients affected by beta-thal int and very rare in thal major patients, does not seem, in this study, to influence the Hb F content in beta thal int patients.

  10. Differential proteolytic activation of factor VIII-von Willebrand factor complex by thrombin.


    Hill-Eubanks, D C; Parker, C G; Lollar, P


    Blood coagulation factor VIII (fVIII) is a plasma protein that is decreased or absent in hemophilia A. It is isolated as a mixture of heterodimers that contain a variably sized heavy chain and a common light chain. Thrombin catalyzes the activation of fVIII in a reaction that is associated with cleavages in both types of chain. We isolated a serine protease from Bothrops jararacussu snake venom that catalyzes thrombin-like heavy-chain cleavage but not light-chain cleavage in porcine fVIII as ...

  11. Hb TAYBE: clinical and morphological findings IN 43 patients. (United States)

    Koren, Ariel; Levin, Carina; Zalman, Luci; Palmor, Haya; Filon, Dvora; Chubar, Evgeny; Resnitzky, Peretz; Bennett, Michael


    Hereditary sequence variants in globin genes are usually silent and are rarer in α-globin chains than β-globin chains. Some may lead to an unstable protein with a hemolytic or thalassemic phenotype. Hb Taybe is an unstable α-chain hemoglobin variant caused by the deletion of a threonine residue at codon 38 or 39 of the α1 globin gene. This deletion results in a structural abnormality that affects the α1 β2 contact and the α1 β1 interface, producing a highly unstable Hb. We describe the clinical, laboratory, and morphological characteristics of 43 patients with Hb Taybe, sixteen of whom are heterozygous, eight are homozygous, and nineteen are double heterozygous for Hb Taybe and other α-gene mutations or deletions. The clinical presentation is very variable from a mild hemolytic anemia to the need for red cell transfusion. Morphological characteristics include erythroid hyperplasia, defective hemoglobin production, and dyserythropoietic features. On electron microscopy dyserythropoiesis and cytoplasmic precipitation of globin compatible optical dense material is seen. This is the largest report of Hb Taybe patients. Previous reported cohorts are not related to these cases. We conclude that patients carrying Hb Taybe have a unique hematological and clinical phenotype distinct from other hemoglobinopathies and from congenital dyserythropoietic anemia. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Rubber particle proteins, HbREF and HbSRPP, show different interactions with model membranes. (United States)

    Berthelot, Karine; Lecomte, Sophie; Estevez, Yannick; Zhendre, Vanessa; Henry, Sarah; Thévenot, Julie; Dufourc, Erick J; Alves, Isabel D; Peruch, Frédéric


    The biomembrane surrounding rubber particles from the hevea latex is well known for its content of numerous allergen proteins. HbREF (Hevb1) and HbSRPP (Hevb3) are major components, linked on rubber particles, and they have been shown to be involved in rubber synthesis or quality (mass regulation), but their exact function is still to be determined. In this study we highlighted the different modes of interactions of both recombinant proteins with various membrane models (lipid monolayers, liposomes or supported bilayers, and multilamellar vesicles) to mimic the latex particle membrane. We combined various biophysical methods (polarization-modulation-infrared reflection-adsorption spectroscopy (PM-IRRAS)/ellipsometry, attenuated-total reflectance Fourier-transform infrared (ATR-FTIR), solid-state nuclear magnetic resonance (NMR), plasmon waveguide resonance (PWR), fluorescence spectroscopy) to elucidate their interactions. Small rubber particle protein (SRPP) shows less affinity than rubber elongation factor (REF) for the membranes but displays a kind of "covering" effect on the lipid headgroups without disturbing the membrane integrity. Its structure is conserved in the presence of lipids. Contrarily, REF demonstrates higher membrane affinity with changes in its aggregation properties, the amyloid nature of REF, which we previously reported, is not favored in the presence of lipids. REF binds and inserts into membranes. The membrane integrity is highly perturbed, and we suspect that REF is even able to remove lipids from the membrane leading to the formation of mixed micelles. These two homologous proteins show affinity to all membrane models tested but neatly differ in their interacting features. This could imply differential roles on the surface of rubber particles. © 2013.

  13. HB-Line Plutonium Oxide Data Collection Strategy

    Energy Technology Data Exchange (ETDEWEB)

    Watkins, R. [Savannah River Nuclear Solutions; Varble, J. [Savannah River Nuclear Solutions; Jordan, J. [Savannah River Nuclear Solutions


    HB-Line and H-Canyon will handle and process plutonium material to produce plutonium oxide for feed to the Mixed Oxide Fuel Fabrication Facility (MFFF). However, the plutonium oxide product will not be transferred to the MFFF directly from HB-Line until it is packaged into a qualified DOE-STD-3013-2012 container. In the interim, HB-Line will load plutonium oxide into an inner, filtered can. The inner can will be placed in a filtered bag, which will be loaded into a filtered outer can. The outer can will be loaded into a certified 9975 with getter assembly in compliance with onsite transportation requirement, for subsequent storage and transfer to the K-Area Complex (KAC). After DOE-STD-3013-2012 container packaging capabilities are established, the product will be returned to HB-Line to be packaged into a qualified DOE-STD-3013-2012 container. To support the transfer of plutonium oxide to KAC and then eventually to MFFF, various material and packaging data will have to be collected and retained. In addition, data from initial HB-Line processing operations will be needed to support future DOE-STD-3013-2012 qualification as amended by the HB-Line DOE Standard equivalency. As production increases, the volume of data to collect will increase. The HB-Line data collected will be in the form of paper copies and electronic media. Paper copy data will, at a minimum, consist of facility procedures, nonconformance reports (NCRs), and DCS print outs. Electronic data will be in the form of Adobe portable document formats (PDFs). Collecting all the required data for each plutonium oxide can will be no small effort for HB-Line, and will become more challenging once the maximum annual oxide production throughput is achieved due to the sheer volume of data to be collected. The majority of the data collected will be in the form of facility procedures, DCS print outs, and laboratory results. To facilitate complete collection of this data, a traveler form will be developed which

  14. War and peace: Factor VIII and the adaptive immune response. (United States)

    Georgescu, Maria T; Lai, Jesse D; Hough, Christine; Lillicrap, David


    The development of neutralizing anti-factor VIII (FVIII) antibodies (inhibitors) remains a major challenge for FVIII replacement therapy in hemophilia A patients. The adaptive immune response plays a crucial role in the development and maintenance of inhibitors. In this review, we focus on our current understanding of FVIII interactions with cells of the adaptive immune system and the phenotype of the resultant response. Additionally, we examine both current and novel FVIII tolerance induction methods that function at the level of the adaptive immune response. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Factor VIII therapy for hemophilia A: current and future issues. (United States)

    Aledort, Louis; Ljung, Rolf; Mann, Kenneth; Pipe, Steven


    Hemophilia A is a congenital, recessive, X-linked bleeding disorder that is managed with infusions of plasma-derived or recombinant factor (F) VIII. The primary considerations in FVIII replacement therapy today are the: 1) immunogenicity of FVIII concentrates, 2) role of longer-acting FVIII products, 3) prophylactic use of FVIII in children and adults with severe hemophilia A, and 4) affordability and availability of FVIII products. Improving patient outcomes by increasing the use of FVIII prophylaxis, preventing or eliminating FVIII inhibitors, and expanding access to FVIII concentrates in developing countries are the major challenges confronting clinicians who care for patients with hemophilia A.

  16. Factor VIII and transmissible spongiform encephalopathy: the case for safety. (United States)

    Cervenakova, L; Brown, P; Hammond, D J; Lee, C A; Saenko, E L


    Haemophilia A is the most common inherited bleeding disorder, caused by a deficiency in coagulation factor VIII (FVIII). Current treatment of haemophilia A is based on repeated infusions of plasma-derived FVIII concentrate or of recombinant FVIII, which may be exposed to plasma-derived material of human or animal origin used in its tissue culture production process. We review epidemiological and experimental studies relevant to blood infectivity in the transmissible spongiform encephalopathies (TSEs, or 'prion' diseases), and evaluate the hypothetical risk of TSE transmission through treatment with plasma-derived or recombinant FVIII.


    Directory of Open Access Journals (Sweden)

    Toni Hidayat


    Full Text Available This study was a classroom action research which aims to investigate how the implementation of guided discovery learning can improve students’ activeness and attainment in the class VIII of Laboraturium UM Senior High School Malang city. The study subject was Class VIII that consists of 36 students, year 2016/2017. This study consisted of two cycles, and the data was collected from the result of the final test, observation, and interview. Based on the research of cycle I, the students’ activeness with mean scores of the meeting I, II, III was 78.88%, 79%, 86.6% respectively. The students’ activeness on cycle II, the mean scores of analyst meeting V and VI were 89.22% and 92.24% respectively. The result of Mathematics learning was increased, it is shown on the test mean of the cycle I that was achieved by 36 students with the percentage of successful learning 83 %. On the cycle test II, the average of 36 gained 82 (score with 7.2 increased from the score mean of the cycle I and with classical mastery learning cycle II 88.88%. Penelitian ini merupakan Penelitian Tindakan Kelas (PTK yang bertujuan untuk mengetahui bagaimana penerapan metode penemuan terbimbing yang dapat meningkatan keaktifan dan hasil belajar siswa kelas VIII SMP Laboratorium UM Kota Malang. Subjek penelitian ini ialah siswa kelas VIII yang berjumlah 36 siswa tahun pelajaran 2016/2017. Penelitian ini terdiri atas dua siklus dan data dikumpulkan dari hasil tes akhir tindakan, observasi, dan wawancara. Berdasarakan hasil penelitian pada siklus I, keaktifan siswa siswa dengan skor rata-rata pertemuan I, II, III adalah 78,88% 79,%, dan 86,6%. Aktivitas siswa pada siklus II, rata-rata skor pengamat pertemuan V dan VI berturut-turut 89,22 % dan 92,24%. Hasil belajar matematika siswa meningkat, hal ini terlihat bahwa rata-rata tes siklus I yang diperoleh 36 siswa sebesar 74,8 dengan presentase keberhasilan belajar 83,33%. Pada tes siklus II rata-rata nilai menjadi 82 dengan

  18. A rare combination: Combined factor V and factor VIII deficiency

    Directory of Open Access Journals (Sweden)

    Başak Ünver Koluman


    Full Text Available Combined factor V (FV and factor VIII (FVIII deficiency is a rare factor deficiency with mild-moderate hemorrhage. It is an autosomal recessive coagulation disorder . Prolonged prothrombin time and partial thromboplastic time is characteristic, platelet count remains in normal ranges. The main stay of treatment is to control the hemorrhage. Fresh frozen plasma, desmopressin, specific FVIII concentrates (plasma- derived or recombinant may be used. Being very rare in the general population, we present a case with a combined FV and FVIII deficiency. J Clin Exp Invest 2014; 5 (2: 323-325

  19. Haemoglobin J-Baltimore can be detected by HbA1c electropherogram but with underestimated HbA1c value. (United States)

    Brunel, Valéry; Lahary, Agnčs; Chagraoui, Abdeslam; Thuillez, Christian


    Glycated haemoglobin (HbA(1c)) is considered the gold standard for assessing diabetes compensation and treatment. In addition, fortuitous detection of haemoglobin variants during HbA1c measurement is not rare. Recently, two publications reported different conclusions on accuracy of HbA(1c) value using capillary electrophoresis method in presence of haemoglobin J-Baltimore (HbJ).
Here we describe the fortuitous detection of unknown HbJ using capillary electrophoresis for measurement of HbA(1c). A patient followed for gestational diabetes in our laboratory presented unknown haemoglobin on Capillarys 2 Flex Piercing analyser which was identified as HbJ. HbJ is not associated with haematological abnormalities. High Performance Liquid Chromatography methods are known to possibly underestimate HbA(1c) value in the presence of this variant. This variant and its glycated form are clearly distinguished on electropherogram but HbJ was responsible for underestimating the true area of HbA(1c).
 Capillary electrophoresis is a good method for detecting HbJ but does not seem suitable for evaluation of HbA(1C) value in patients in presence of HbJ variant.

  20. Detection of compound heterozygous of hb constant spring and hb q-Thailand by capillary electrophoresis and high performance liquid chromatography. (United States)

    Pornprasert, Sakorn; Punyamung, Manoo


    A capillary electrophoresis (CE) has proven to be superior to a high performance liquid chromatography (HPLC) in the detection of hemoglobin Constant Spring (Hb CS). Thus the aim of this study was to analyze the efficacy of CE and HPLC for the detection of Hb CS in samples with compound heterozygous of Hb CS and Hb Q-Thailand. Hemoglobin analysis was performed in blood samples of 2 patients with compound heterozygous of Hb CS and Hb Q-Thailand by using HPLC and CE. The HPLC chromatogram and CE electrophoregram of the two techniques were compared. Hb CS was not found on HPLC chromatogram while Hb QA2 (α2 (QT)δ2), a derivative of Hb Q-Thailand, was presented at the retention time of 4.70-4.80 min and it was close to the retention time of Hb CS. On CE electrophoregram, Hb CS was presented at zone 2 (Z2) and it was distinctly separated from Hb QA2 which was presented at Z1. Therefore, CE was more efficient to the HPLC for diagnosis of compound heterozygous of Hb CS and Hb Q-Thailand.

  1. A method comparison study between two hemoglobinometer models (Hemocue Hb 301 and Hb 201+) to measure hemoglobin concentrations and estimate anemia prevalence among women in Preah Vihear, Cambodia. (United States)

    Rappaport, A I; Karakochuk, C D; Whitfield, K C; Kheang, K M; Green, T J


    Hemoglobin (Hb) concentration is often measured in global health and nutrition surveys to determine anemia prevalence using a portable hemoglobinometer such as the Hemocue® Hb 201+. More recently, a newer model was released (Hemocue Hb 301) utilizing slightly different methods to measure Hb as compared to the older model. The objective was to measure bias and concordance between Hb concentrations using the Hemocue Hb 301 and Hb 201+ models in a rural field setting. Hemoglobin (Hb) concentration was measured using one finger prick of blood (approximately 10 μL) from 175 Cambodian women (18-49 years) using three Hemocue Hb 201+ and three Hb 301 machines. Bias and concordance were measured and plotted. Overall, mean ± SD Hb concentration was 116 ± 13 g/L using the Hb 201+ and 118 ± 12 g/L using the Hb 301; and anemia prevalence (Hb < 120 g/L) was 58% (n = 102) and 58% (n = 101), respectively. Overall bias ± SD was 2.0 ± 10.5 g/L and concordance (95% CI) was 0.63 (0.54, 0.72). Despite the 2 g/L bias detected between models, anemia prevalence was very similar in both models. The two models measured anemia prevalence comparably in this population of women in rural Cambodia. © 2016 John Wiley & Sons Ltd.

  2. Why the DNA self-depurination mechanism operates in HB-β but not in β-globin paralogs HB-δ, HB-ɛ1, HB-γ1 and HB-γ2. (United States)

    Amosova, Olga; Alvarez-Dominguez, Juan R; Fresco, Jacques R


    The human β-globin, δ-globin and ɛ-globin genes contain almost identical coding strand sequences centered about codon 6 having potential to form a stem-loop with a 5'GAGG loop. Provided with a sufficiently stable stem, such a structure can self-catalyze depurination of the loop 5'G residue, leading to a potential mutation hotspot. Previously, we showed that such a hotspot exists about codon 6 of β-globin, with by far the highest incidence of mutations across the gene, including those responsible for 6 anemias (notably Sickle Cell Anemia) and β-thalassemias. In contrast, we show here that despite identical loop sequences, there is no mutational hotspot in the δ- or ɛ1-globin potential self-depurination sites, which differ by only one or two base pairs in the stem region from that of the β-globin gene. These differences result in either one or two additional mismatches in the potential 7-base pair-forming stem region, thereby weakening its stability, so that either DNA cruciform extrusion from the duplex is rendered ineffective or the lifetime of the stem-loop becomes too short to permit self-catalysis to occur. Having that same loop sequence, paralogs HB-γ1 and HB-γ2 totally lack stem-forming potential. Hence the absence in δ- and ɛ1-globin genes of a mutational hotspot in what must now be viewed as non-functional homologs of the self-depurination site in β-globin. Such stem-destabilizing variants appeared early among vertebrates and remained conserved among mammals and primates. Thus, this study has revealed conserved sequence determinants of self-catalytic DNA depurination associated with variability of mutation incidence among human β-globin paralogs. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Hemoglobin Constant Spring (Hb CS) Missed by HPLC in an Hb E Trait Pregnancy Resulting in Hb H-CS Disease in a Thai Girl: Utility of Capillary Electrophoresis. (United States)

    Pornprasert, Sakorn; Saoboontan, Supansa; Wiengkum, Thanatcha


    Hemoglobin Constant Spring [Hb CS; α142, Term→Gln (TAA>CAA IN α2)] is often missed by routine laboratory testing, especially in subjects with co-inheritance of β-thalassemia or β-variants. We reported the case of a 1-year-old female with Hb H-CS disease who was born from a father with heterozygous of α-thalassemia-1 Southeast Asian type deletion and a mother with the combination of Hb CS and Hb E [β26 (B8) Glu→Lys, GAG>AAG] trait. A very tiny peak of Hb CS of the mother was easily ignored on the high performance liquid chromatography chromatogram while it was clearly seen on the capillary electrophoresis (CE) electrophoregram. Therefore, the CE is useful in screening for heterozygous Hb CS in a person with Hb E trait. This is of potential benefit for prevention of new cases of Hb H-CS disease.

  4. Coinheritance of High Oxygen Affinity Hb Helsinki [HBB: c.248A>T; β82(EF6)Lys→Met] with Hb H Disease. (United States)

    Lee, Shir-Ying; Goh, Jia-Hui; Tan, Karen M L; Liu, Te-Chih


    Hb Helsinki [HBB: c.248A>T; β82(EF6)Lys→Met] is a high oxygen affinity hemoglobin (Hb) causing polycythemia, whereas Hb H (β4) disease causes mild to severe chronic hemolytic anemia. The clinical characteristics, gel electrophoresis, capillary electrophoresis (CE) and molecular genotyping of a case of Hb Helsinki coinherited with Hb H disease in an ethnic Malay is described, illustrating the interaction between the β-globin variant and coinheritance of three α gene deletions. The proband was asymptomatic, exhibited microcytosis and a normal with Hb value.

  5. Evidence for the formation of sodium hassate(VIII)

    Energy Technology Data Exchange (ETDEWEB)

    Zweidorf, A. von [Inst. fuer Kernchemie, Johannes Gutenberg-Univ. Mainz, Mainz (Germany); Gesellschaft fuer Schwerionenforschung mbH, Darmstadt (Germany); Angert, R.; Bruechle, W.; Buerger, S.; Eberhardt, K.; Eichler, R.; Hummrich, H.; Jaeger, E.; Kling, H.O.; Kratz, J.V.; Kuczewski, B.; Langrock, G.; Mendel, M.; Rieth, U.; Schaedel, M.; Schausten, B.; Schimpf, E.; Thoerle, P.; Trautmann, N.; Tsukada, K.; Wiehl, N.; Wirth, G.


    Hassium, element 108, was produced in the fusion reaction between {sup 26}Mg and {sup 248}Cm. The hassium recoils were oxidized in-situ to a highly volatile oxide, presumably HsO{sub 4}, and were transported in a mixture of He and O{sub 2} to a deposition and detection system. The latter consisted of 16 silicon PIN-photodiodes facing a layer of NaOH, which served, in the presence of a certain partial pressure of water in the transport gas, as reactive surface for the deposition of the volatile tetroxides. Six correlated {alpha}-decay chains of Hs were detected in the first 5 detectors centred around detection position 3. In analogy to OsO{sub 4}, which forms Na{sub 2}[OsO{sub 4}(OH){sub 2}], an osmate(VIII), with aqueous NaOH, HsO{sub 4} presumably was deposited as Na{sub 2}[HsO{sub 4}(OH){sub 2}], a hassate(VIII). (orig.)

  6. Aristóteles y las series causales infinitas en Física VII y VIII

    Directory of Open Access Journals (Sweden)

    Alberto Ross


    Full Text Available The aim of this paper is to show that we have at least two different arguments that prove the First Motor's existence. Even though there are coincidences between Physics VII 1 and VIII 5, their arguments are not identical. Physics VII argue the impossibility of an infinite movement in a finite time and VIII 5 the necessity of a "principal" cause.

  7. Effectiveness of Mind Mapping in English Teaching among VIII Standard Students (United States)

    Hallen, D.; Sangeetha, N.


    The aim of the study is to find out the effectiveness of mind mapping technique over conventional method in teaching English at high school level (VIII), in terms of Control and Experimental group. The sample of the study comprised, 60 VIII Standard students in Tiruchendur Taluk. Mind Maps and Achievement Test (Pretest & Posttest) were…

  8. 40 CFR Appendix Viii to Part 85 - Vehicle and Engine Parameters and Specifications (United States)


    .... a. Control parameters and calibrations. b. EGR valve flow calibration. 3. Catalytic converter system.... a. Control parameters and calibrations. b. EGR valve flow calibration. 3. Catalytic converter system... Specifications VIII Appendix VIII to Part 85 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED...

  9. 40 CFR Appendix Viii to Part 266 - Organic Compounds for Which Residues Must Be Analyzed (United States)


    ... AGENCY (CONTINUED) SOLID WASTES (CONTINUED) STANDARDS FOR THE MANAGEMENT OF SPECIFIC HAZARDOUS WASTES AND SPECIFIC TYPES OF HAZARDOUS WASTE MANAGEMENT FACILITIES Pt. 266, App. VIII Appendix VIII to Part 266... residues collected from areas downstream of the combustion chamber (e.g., ductwork, boiler tubes, heat...

  10. Hb Southern Italy: coexistence of two missence mutations (the Hb Sun Prairie 2 130 Ala Pro and Hb Caserta 2 26 Ala Thr) in a single HBA2 gene

    National Research Council Canada - National Science Library

    Passarello, Cristina; Giambona, Antonino; Prossomariti, Luciano; Ammirabile, Massimiliano; Pucci, Piero; Renda, Disma; Pagano, Leonilde; Maggio, Aurelio


    ... (Campania and Sicily). This new double mutant form of haemoglobin is called Hb Southern Italy and originated from the coexistence of two known mutations occurring in the same globin gene, HBA2 26 G→A (Hb Caserta) and HBA2 130 G→C (Hb Sun Prairie...

  11. Incidence of hemoglobinopathies and thalassemias in Northern Alberta. Establishment of reference intervals for HbF and HbA2. (United States)

    Rodriguez-Capote, Karina; Higgins, Trefor N


    The aims of this study were to identify the incidence of hemoglobinopathies and thalassemias in Northern Alberta and calculate the reference intervals (RI) for hemoglobin (Hb) HbF and HbA2. A retrospective ad-hoc analysis of the structural Hb variants and thalassemias identified on patients who had a hemoglobinopathy/thalassemia investigation performed between February 1 to December 31, 2013. Results were extracted from the Laboratory Information System. Statistical analysis was performed using MedCalc® version for Windows software. 6616 hemoglobinopathy/thalassemia investigations and HbS screens were physician requested and 602 Hb variants were fortuitously found during HbA1c analysis. 3438 were interpreted as "normal" and 532 were classified as iron deficient. 3306 individuals, with age ranging from 3 to 92 years were included in the RI calculation. HbA2 RI was 2.3% to 3.4% and HbF 0.0% to 1.8%. 524 and 423 α and β thalassemia traits respectively were identified. Additionally ten δβ thalassemia traits and twelve cases of HbH disease were identified. Regarding hemoglobinopathies, 7% were classified as α-chain variants and 93% as β-chain variants with HbS (46%), HbE (16%), HbD Punjab (8%) and HbC (7%) traits being the most prevalent. We also documented 20 homozygous hemoglobinopathies and 36 compound/double heterozygous hemoglobinopathies. A wide diversity of hemoglobinopathies is found in the Northern Alberta population, 80% of the hemoglobinopathies were found as a reflex to HbA1c testing. Reference intervals for HbF and HbA2 were established. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  12. HB Puerta del Sol [HBA1:c.148A>C], HB Valdecilla [HBA2:c.3G>T], HB Gran Vía [HBA2:c.98T>G], HB Macarena [HBA2:c.358C>T] and HB El Retiro [HBA2:c.364_366dupGTG]: description of five new hemoglobinopathies. (United States)

    de la Fuente-Gonzalo, Félix; Nieto, Jorge M; Velasco, Diego; Cela, Elena; Pérez, Germán; Fernández-Teijeiro, Ana; Escudero, Antonio; Villegas, Ana; González-Fernández, Fernando A; Ropero, Paloma


    Structural hemoglobinopathies do not usually have a clinical impact, but they can interfere with the analytical determination of some parameters, such as the glycated hemoglobin in diabetic patients. Thalassemias represent a serious health problem in areas where their incidence is high. The defects in the post-translational modifications produce hyper-unstable hemoglobin that is not detected by most of electrophoretic or chromatographic methods that are available so far. We studied seven patients who belong to six unrelated families. The first two families were studied because they had peak abnormal hemoglobin (Hb) during routine analytical assays. The other four families were studied because they had microcytosis and hypochromia with normal HbA2 and HbF without iron deficiency. HbA2 and F quantification and abnormal Hb separation were performed by chromatographic and electrophoretic methods. The molecular characterization was performed using specific sequencing. The Hb Puerta del Sol presents electrophoretic mobility and elution in HPLC that is different from HbA and similar to HbS. The electrophoretic and chromatographic profiles of the four other variants are normal and do not show any anomalies, and their identification was only possible with sequencing. Some variants, such as Hb Valdecilla, Hb Gran Vía, Hb Macarena and Hb El Retiro, have significant clinical impact when they are associated with other forms of α-thalassemia, which could lead to more serious forms of this group of pathologies as for HbH disease. Therefore, it is important to maintain an adequate program for screening these diseases in countries where the prevalence is high to prevent the occurrence of severe forms.

  13. Detection of fetal hemoglobin (HbF) using the G8 glycohemoglobin analyzer. (United States)

    Jeon, Byung Ryul


    Abnormal HbF concentration has been proposed as a marker of solid tumor and myelodysplastic syndrome. As HbA1c is tested widely for glycemic control monitoring, some commercial glycated hemoglobin assays can provide additional information about these hemoglobin concentrations. However, few studies have investigated the clinical significance of increased HbF in current practice. Between January 2012 and December 2012, HbAlc results, tested in the Department of Laboratory Medicine at Soonchunhyang University Bucheon Hospital, were analyzed. HbAlc was measured using a G8 Glycohemoglobin Analyzer (Tosho Bioscience, Tokyo, Japan) in the 1.6 minutes HbAlc mode. A total of 13,866 specimens from 9,545 patients were tested. The median HbF concentration was 0.7%, the 99.5th percentile was 3.2%, and 73 samples from 56 patients were > 3.2%. Among these patients, 37.5% (21/56) had malignancies: 16 had solid cancer and 5 had hematologic malignancies. The maximum HbF observed was 8.2% and elevated HbF showed no evidence of interference with the HbAlc test. However, the minimum HbF and LA1C+ fraction increased with increasing HbAlc, suggesting interference by elevated HbAlc. Care must be taken when interpreting HbF concentrations in samples with high HbAlc values determined using the HbA1c mode of the G8 Glycohemoglobin Analyzer.

  14. Determinação de HbA1c por CLAE: interferência de variantes de hemoglobinas S e C e alta concentração de HbF HbA1c determination by HPLC: interference of hemoglobin variants HbS, HbC and HbF high concentration

    Directory of Open Access Journals (Sweden)

    Maria das Graças Santos Menezes


    Full Text Available INTRODUÇÃO: O diabetes mellitus (DM é considerado um problema importante de saúde pública; possui prevalência elevada e nos últimos anos observa-se aumento progressivo na sua incidência. OBJETIVO: verificar possíveis variações na concentração de hemoglobina (Hb glicada (HbA1c na presença de Hbs S e C e avaliar o impacto da redução da HbA1c na avaliação clínica e no monitoramento do paciente diabético. MATERIAL E MÉTODOS: Foram incluídos no estudo, 150 indivíduos diabéticos oriundos da cidade de Salvador, Bahia, de ambos os gêneros, com idade média de 56 anos. Foram determinadas a glicemia de jejum e a HbA1c por metodologia de oxidase-peroxidase e cromatografia líquida de alta eficiência (CLAE, respectivamente. RESULTADOS: Foram observadas variações na concentração da HbA1c em função da presença de variantes de Hb, como 7,85%, AA; 7,30%, AS e 7,15%, AC. DISCUSSÃO E CONCLUSÃO: A metodologia analítica a ser utilizada para determinação de HbA1c deve ser escolhida com base nas características gerais da população atendida e nas comorbidades associadas, pois a presença de Hbs S e C ocasiona reduções significativas de glicação. Essa redução pode levar a interpretações clínicas inadequadas relativas ao controle glicêmico dos pacientes.INTRODUCTION: Diabetes mellitus (DM is considered an important public health problem. It is highly prevalent and its incidence has progressively increased in recent years. OBJECTIVE: To verify possible variations of glycated hemoglobin (HbA1c concentration in the presence of Hb S and Hb C and to evaluate the impact of HbA1c reduction on clinical evaluation and monitoring of diabetic patients. MATERIAL AND METHODS: This study comprised 150 diabetic individuals from Salvador city, Bahia, from both genders and average age of 56 years old. Fast blood glucose and HbA1c were determined by oxidase-peroxidase and high-performance liquid chromatography (HPLC methods, respectively

  15. Preparation of hemoglobin (Hb) imprinted polymer by Hb catalyzed eATRP and its application in biosensor. (United States)

    Sun, Yue; Du, Hongying; Lan, Yuting; Wang, Wenjing; Liang, Yuejian; Feng, Chunliang; Yang, Mei


    Molecularly imprinted polymer (MIP) was prepared on the surface of Au electrode by electrochemically mediated atom transfer radical polymerization (eATRP) with hemoglobin (Hb) both as catalyst and template molecule. Firstly, the condition for eATRP such as the potential, time and Hb concentration were selected and determined to be -0.51 V, 120 min and 20mg/mL, respectively. Further, the electrode modified with MIP (MIP/Au) was carefully examined by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and scanning electron microscope (SEM). Finally, the MIP/Au electrode was used as a biosensor and successfully applied for the determination of Hb by differential pulse voltammetry (DPV) measurement. The results of experiments showed that the proposed biosensor displayed a broader linear range and a lower detection limit for Hb determination when it was compared to those Hb sensors based on MIP. The linear range was from 1.0 × 10(-10) to 1.0 × 10(1)mg/L with a detection limit of 7.8 × 10(-11)mg/L (S/N=3.3). In a word, the work of this paper established a useful way for the preparation and application of biosensor based on protein imprinted polymers. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Measurement of HbA1c and HbA2 by Capillarys 2 Flex Piercing HbA1c programme for simultaneous management of diabetes and screening for thalassemia


    Ke, Peifeng; Liu, Jiawei; Chao, Yan; Wu, Xiaobin; Xiong, Yujuan; Lin, Li; Wan, Zemin; Wu, Xinzhong; Xu, Jianhua; Zhuang, Junhua; Huang, Xianzhang


    Introduction: Thalassemia could interfere with some assays for haemoglobin A1c (HbA1c) measurement, therefore, it is useful to be able to screen for thalassemia while measuring HbA1c. We used Capillarys 2 Flex Piercing (Capillarys 2FP) HbA1c programme to simultaneously measure HbA1c and screen for thalassemia. Materials and methods: Samples from 498 normal controls and 175 thalassemia patients were analysed by Capillarys 2FP HbA1c programme (Sebia, France). For method comparison, ...

  17. HB+ prepares for insertion into the CMS solenoid

    CERN Multimedia

    Dave Barney, CERN


    With calibration of the first half of the barrel Hadron Calorimeter (HB+) complete (using a radioactive source), preparations begin for its insertion into the solenoid for the Magnet Test and Cosmic Challenge (MTCC). It was moved out of its alcove at the beginning of March - a non-trivial (but completely successful) operation due to the proximity of one of the barrel yoke rings (YB+1). The other half of the barrel Hadron Calorimeter (HB-) and one of the endcaps (HE+) should also be calibrated before the MTCC.

  18. Hb Tianshui (HBB: C.119A > G) in Compound Heterozygosity with Hb S (HBB: C.20A > T) from Odisha, India. (United States)

    Meher, Satyabrata; Dehury, Snehadhini; Mohanty, Pradeep Kumar; Patel, Siris; Pattanayak, Chinmayee; Bhattacharya, Subhra; Das, Kishalaya; Sarkar, Biswanath


    We describe here a rare β-globin gene variant, Hb Tianshui [β39(C5)Glu→Arg; HBB: c.119A > G], detected during routine screening in Odisha, India. This is the second report of Hb Tianshui and the first to describe the cation exchange high performance liquid chromatography (HPLC) and DNA studies of two cases of this variant. Both cases had coinherited Hb S (HBB: c.20A > T) but none presented with typical symptoms of sickle cell disease. One of the cases was heterozygous for a common α-thalassemia (α-thal) allele (-α(3.7)) (rightward) (NG_000006.1: g.34164_37967del3804) and marginally raised Hb F percentage, while the other Hb S/Hb Tianshui case was completely benign and healthy. An atypical Asian Indian haplotype [+ - + - +] could be assigned to the Hb Tianshui variant. Hb Tianshui seems to mimic a few other Hb variants in cation exchange HPLC. However, we report two specific patterns in the chromatograms that are characteristic to Hb Tianshui. Combining an alkaline electrophoresis result with cation exchange HPLC at screening would be preferred to detect this rare variant, especially in regions with considerable frequency of Hb E [β26(B8)Glu→Lys; HBB: c.79G > A] or Hb S.

  19. Maternally transferred anti-factor VIII IgG reduce the anti-factor VIII humoral immune response in factor VIII-deficient mice. (United States)

    Meslier, Yann; André, Sébastien; Teyssandier, Maud; Kaveri, Srinivas V; Lacroix-Desmazes, Sébastien


    Replacement therapy with exogenous factor VIII (FVIII) to treat haemorrhages or used in prophylaxis induces inhibitory anti-FVIII immunoglobulin G (IgG) in some patients with haemophilia A. Therapeutic strategies to prevent the onset of the deleterious anti-FVIII immune response are still lacking. Maternal IgG is transferred to the offspring during fetal and neonatal life. While protecting the offspring from bacterial and viral infections, maternal IgG may alter the repertoires of T and B lymphocytes, and may impair vaccination in early infancy. Using haemophilic mice, we demonstrate that the transfer of maternal anti-FVIII IgG modulates the onset of anti-FVIII inhibitory IgG in early adulthood. The protective effect is reproduced upon reconstitution of naive mice with anti-FVIII IgG, suggesting that the reduced ability to mount an anti-FVIII immune response is the result of an interference between circulating anti-FVIII IgG and the administered FVIII rather than to a profound remodelling of lymphocyte repertoires occurring during the ontogeny of the immune system. © 2010 The Authors. Immunology © 2010 Blackwell Publishing Ltd.

  20. Acquired factor VIII inhibitor syndrome: A rare cause of hematuria

    Directory of Open Access Journals (Sweden)

    Muthuvel Seral Kannan


    Full Text Available A 50-year-old woman presented with gross hematuria for 1 month. Clinical examinations, laboratory investigations, ultrasound and contrast computed tomography were normal, except anemia. Cystoscopy revealed bloody efflux from the right side. Retrograde pyelogram showed filling defect in the renal pelvis and biopsy was inconclusive. Renal angiogram was normal. She developed ecchymosis on the right thigh and arm with elevated activated partial thromboplastin time. The partial thromboplastin time correction study and Bethesda study confirmed the presence of acquired factor VIII inhibitor (acquired hemophilia. With flexible ureterorenoscopy, the mass in the renal pelvis was removed and its histopathology revealed clotted blood. The patient was subsequently managed with steroids and Factor eight inhibitor bypass activity.

  1. A bispecific antibody mimicking factor VIII in hemophilia A therapy. (United States)

    Nogami, Keiji


    Serious issues in current hemostatic treatment of hemophilia A are the requirement for frequent intravenous administrations of factor (F) VIII, FVIII inhibitor development, and hemostatic treatment for patients with this inhibitor. For the purpose of overcoming these challenges, the FVIIIa-substituting bispecific antibody against FIXa/FX (ACE910, INN emicizumab) was produced. Emicizumab demonstrated marked hemostatic effects on both ongoing and spontaneous joint bleeding in the acquired hemophilia A primate model. The clinical phase 1 study designed to assess the pharmacokinetics, pharmacodynamics and safety of emicizumab has been initiated. Severe emicizumab-related adverse events were minimal. The t1/2 was approximately 30 days, and bleeding events were significantly decreased by weekly subcutaneous administration in severe hemophilia A patients, independently of the presence of the inhibitor. Currently, the phase 1/2 extension study is ongoing. We anticipate that emicizumab will show the benefits of prophylactic efficacy with subcutaneous administration at a much lower frequency.

  2. Molecular characterization of HbEREBP2, a jasmonateresponsive ...

    African Journals Online (AJOL)

    Transcription factors of AP2/ERF superfamily are generally involved in defense responses of plants to biotic and abiotic stresses. Although, defense proteins are present in abundance in laticifers of rubber tree, little is known about their transcriptional regulation. In this study, a full length cDNA, referred to as HbEREBP2 was ...


    African Journals Online (AJOL)

    increase in haemoglobin F inhibits polymerization of sickle haemoglobin. The varying levels of foetal haemoglobin in erythro- cytes account for a larger part of clinical heterogene-. FOETAL HAEMOGLOBIN (HbF) STATUS IN ADULT SICKLE CELL ANAEMIA. PATIENTS IN IBADAN, NIGERIA. *J.A. Olaniyi; +O.G Arinola; ...

  4. Thermo-mechanical model optimization of HB-LED packaging

    NARCIS (Netherlands)

    Yuan, C.A.; Erinc, M.; Gielen, A.W.J.; Waal, A. van der; Driel, W. van; Zhang, K.


    Lighting is an advancing phenomenon both on the technology and on the market level due to the rapid development of the solid state lighting technology. The efforts in improving the efficacy of high brightness LED's (HB-LED) have concentrated on the packaging architecture. Packaging plays a

  5. Registration of Food Barley (Hordeum vulgare L.) Variety HB 1307 ...

    African Journals Online (AJOL)

    Six-rowed food type barley, HB 1307, was developed by Holetta Agricultural Research Center (HARC) from a cross between a landrace line and exotic germplasm (Awra gebs-1 x IBON93/91) and released in 2006 for mid and high altitude areas. The three consecutive years\\' (2002-2004) tests proved its superiority in grain ...

  6. Agnostic Stacking of Intergalactic Doublet Absorption: Measuring the Ne VIII Population (United States)

    Frank, Stephan; Pieri, Matthew M.; Mathur, Smita; Danforth, Charles W.; Michael Shull, J.


    We present a blind search for doublet intergalactic metal absorption with a method dubbed `agnostic stacking'. Using a forward-modelling framework we combine this with direct detections in the literature to measure the overall metal population. We apply this novel approach to the search for Ne VIII absorption in a set of 26 high-quality COS spectra. We probe to an unprecedented low limit of log N>12.3 at 0.47≤z ≤1.34 over a pathlength Δz = 7.36. This method selects apparent absorption without requiring knowledge of its source. Stacking this mixed population dilutes doublet features in composite spectra in a deterministic manner, allowing us to measure the proportion corresponding to Ne VIII absorption. We stack potential Ne VIII absorption in two regimes: absorption too weak to be significant in direct line studies (12.3 13.7). We do not detect Ne VIII absorption in either regime. Combining our measurements with direct detections, we find that the Ne VIII population is reproduced with a power law column density distribution function with slope β = -1.86+0.18-0.26 and normalisation log f_{13.7} = -13.99+0.20-0.23, leading to an incidence rate of strong Ne VIII absorbers dn/dz =1.38+0.97-0.82. We infer a cosmic mass density for Ne VIII gas with 12.3 constituting 4% of the total baryonic mass.

  7. Laboratory parameters provided by Advia 2120 analyser identify structural haemoglobinopathy carriers and discriminate between Hb S trait and Hb C trait. (United States)

    Velasco-Rodríguez, Diego; Alonso-Domínguez, Juan-Manuel; González-Fernández, Fernando-Ataúlfo; Muriel, Alfonso; Abalo, Lorena; Sopeña, María; Villarrubia, Jesús; Ropero, Paloma; Plaza, María Paz; Tenorio, María; Jiménez-Martín, Ana; Moreno, Gemma; Martínez-Nieto, Jorge; de la Fuente-Gonzalo, Félix; Fernández-Escribano, Marina; López-Jiménez, Francisco Javier; Cava, Fernando


    Haemoglobinopathies have spread owing to human migration, and the number of people needing diagnosis and management of these conditions is increasing. Clinicians need to accurately identify carriers and provide adequate genetic counselling in order to prevent the occurrence of homozygous or compound heterozygous offspring. To identify red blood cell (RBC) laboratory parameters that discriminate between structural haemoglobinopathy carriers and healthy subjects, and to compare RBC laboratory indices between HbAS and HbAC individuals. Samples of 500 variant Hb carriers (355 HbAS, 104 HbAC, 19 HbAD, 7 HbAE, 7 HbAO-Arab, 4 α-chain variants and 4 Hb Lepore) and 251 normal controls were run on an Advia 2120 analyser (Siemens). Classic haematological parameters and RBC populations were assessed in all subjects. A multivariable binary logistic regression model was created to predict the probability of a subject carrying any structural haemoglobinopathy. HbAS (n=355, 71%) and HbAC (n=104, 20.8%) subjects were compared. A clinical prediction rule was developed by assigning one point to each of the most efficient variables: mean corpuscular volume (MCV) 13.4%, percentage of microcytic RBCs (%MICRO) >0.7% and the ratio of microcytic RBCs to hypochromic RBCs >0.8. A score of 0, 1, 2, 3 or 4, resulted in a probability of 9.6%, 36.3%, 66.7%, 85.2% or 98.3%, respectively. Among the most frequent variant Hb, HbAC subjects had lower values of parameters related to cell size (MCV, %MICRO) and higher values of parameters related to haemoglobin concentration (MCHC, %HYPER) than HbAS subjects. Coexistence of α-thalassaemia in both HbAS and HbAC individuals resulted in decreased Hb, MCV, MCH and MCHC. Structural haemoglobinopathy should be investigated in subjects belonging to ethnic groups with high prevalence of variant Hb and with a score of 3 or 4. Erythrocytes of HbAC subjects are smaller and denser than those of HbAS subjects. Published by the BMJ Publishing Group Limited. For

  8. Type VIII collagen is elevated in diseases associated with angiogenesis and vascular remodeling

    DEFF Research Database (Denmark)

    Hansen, N. U. B.; Willumsen, N.; Bülow Sand, Jannie Marie


    Objectives Type VIII collagen is involved in angiogenesis and remodeling of arteries. We hypothesized that type VIII collagen was upregulated in diseases associated with vascular remodeling, e.g. pulmonary fibrosis and cancer. In this paper we present the development and validation of a competitive...... performance, and in relevant disease cohorts. The developed ELISA was applied for the assessment of type VIII collagen in serum from patients diagnosed with chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF) and various cancers. Results The C8-C ELISA was technically stable...

  9. Detection of Hb Constant Spring (HBA2: c.427T>C) Heterozygotes in Combination with β-Thalassemia or Hb E Trait by Capillary Electrophoresis. (United States)

    Pornprasert, Sakorn; Saoboontan, Supansa; Punyamung, Manoo


    Hb Constant Spring (Hb CS; HBA2: c.427T>C) is often missed by routine laboratory testing as its mRNA as well as gene product are unstable and presented at a low level in peripheral blood. This study aimed to analyze the efficacy of capillary electrophoresis (CE) for detecting and quantifying of Hb CS in β-thalassemia (β-thal) trait or Hb E (HBB: c.79G>A) trait samples with reduced β-globin chain expression. Thalassemia diagnostic data were reviewed in 2524 blood samples that were submitted to the laboratory of the Associated Medical Sciences Clinical Service Center, Chiang Mai, Thailand for hemoglobinopathy and thalassemia diagnosis. DNA analysis for Hb CS was performed in 322 β-thal trait and 397 Hb E trait samples using the amplification refractory mutation system (ARMS). The CE electropherogram of Hb CS at zone 2 was observed in all five samples with β-thal trait and nine samples with Hb E trait with levels varying from 0.1-2.8 and 0.1-2.3%, respectively. Thus, the CE method proved useful for screening of Hb CS in samples with β-thal trait or Hb E trait, which is essential for providing accurate diagnosis, genetic counseling, prevention and control programs of Hb H-CS disease.

  10. Characterization of a Novel Anti-Human HB-EGF Monoclonal Antibody Applicable for Paraffin-Embedded Tissues and Diagnosis of HB-EGF-Related Cancers. (United States)

    Iwamoto, Ryo; Takagi, Mika; Akatsuka, Jun-Ichi; Ono, Ken-Ichiro; Kishi, Yoshiro; Mekada, Eisuke


    Heparin-binding EGF-like growth factor (HB-EGF) is a member of the EGF family of growth factors that bind to and activate the EGF receptor (EGFR/ErbB1) and ErbB4. HB-EGF plays pivotal roles in pathophysiological processes, including cancer. Thus, monoclonal antibodies (mAbs) for HB-EGF detection could be an important tool in the therapeutic diagnosis of HB-EGF-related cancers and other diseases. However, few mAbs, especially those applicable for immunohistochemistry (IHC), have been established to date. In this study, we generated a clone of hybridoma-derived mAb 2-108 by immunizing mice with recombinant human HB-EGF protein expressed by human cells. The mAb 2-108 specifically bound to human HB-EGF but not to mouse HB-EGF and was successful in immunoblotting, even under reducing conditions, immunoprecipitation, and immunofluorescence for unfixed as well as paraformaldehyde-fixed cells. Notably, this mAb was effective in IHC of paraffin-embedded tumor specimens. Epitope mapping analysis showed that mAb 2-108 recognized the N-terminal prodomain in HB-EGF. These results indicate that this new anti-HB-EGF mAb 2-108 would be useful in the diagnosis of HB-EGF-related cancers and would be a strong tool in both basic and clinical research on HB-EGF.

  11. Contribution of Proton Capture Reactions to the Ascertained ...

    Indian Academy of Sciences (India)

    Upakul Mahanta


    Nov 27, 2017 ... the CMDs have revealed that the GC M4 possesses broadened red giant branches (Marino et al. 2008). On the other hand GC M22 have shown a metallicity unfold and a sophisticated chemical enrichment. More- over M22 is among the most massive galactic globular clusters and its colour-magnitude ...

  12. Microscopic study of proton-capture reactions on unstable nuclei

    CERN Document Server

    Descouvemont, P


    The sup 8 B(p,gamma) sup 9 C, sup 1 sup 1 C(p,gamma) sup 1 sup 2 N and sup 1 sup 3 N(p,gamma) sup 1 sup 4 O capture cross sections are investigated in a microscopic cluster model, with a full p-shell description of the target nuclei. For the sup 8 B(p,gamma) sup 9 C reaction and its mirror, the E1 and E2 components are analyzed. The present model confirms previous microscopic calculations for sup 8 B(p,gamma) sup 9 C and sup 1 sup 3 N(p,gamma) sup 1 sup 4 O, but yields a significant reduction of the sup 1 sup 1 C(p,gamma) sup 1 sup 2 N reaction rate. In each case, the sensitivity with respect to the nucleon-nucleon interaction is evaluated, and shown to be weak.

  13. Contribution of Proton Capture Reactions to the Ascertained ...

    Indian Academy of Sciences (India)

    Such kind of temperature density conditions are probably going to be prevailing within the H-burning shell of evolved stars. The estimated abundances of 19F are then matched with the info that has been determined for a few some metal-poor giants of GC M4, M22,47 Tuc as well as NGC 6397. As far as the comparison ...

  14. HB D Los Angeles in a Brazilian family Hb D Los Angeles em família brasileira

    Directory of Open Access Journals (Sweden)

    Guilherme G. Leoneli


    Full Text Available Inherited disorders of hemoglobin, the most common monogenic disease, are now well understood at the molecular level, knowledge, which has led to considerable improvements in their control and management. The Brazilian population is multiethnic, and the correct characterization of the Hb D is important, mainly because the method available for detection of abnormal hemoglobins, present a migration in the same zone at alkaline pH, for Hb S, D, and G for example. In this paper we studied a family with an abnormal hemoglobin like S in alkaline electrophoresis, by appropriated methods including HPLC and molecular analysis, characterized as hemoglobin D Los Angeles.As doenças hereditária da hemoglobina são as mais comuns doenças monogênicas e atualmente bem conhecidas do ponto de vista molecular, fato este que propiciou um avanço no seu controle e manuseio. A população brasileira caracteriza-se pela multiplicidade étnica e a caracterização da Hb D torna-se importante por este dado, associado ao fato de que os métodos de detecção das hemoglobinopatias comumente não identificam esta fração anormal que apresenta a peculiaridade de migração eletroforéticia em pH alcalino na mesma zona observada nas Hb S e G. Neste relato é apresentado um estudo familiar no qual é empregada metodologia adequada, o HLPC, que permite a identificação da Hb D.

  15. The significance of disulfide bonding in biological activity of HB-EGF, a mutagenesis approach


    Hoskins, J.T.; Zhou, Z.; Harding, P A


    A site-directed mutagenesis approach was taken to disrupt each of 3 disulfide bonds within human HB-EGF by substituting serine for both cysteine residues that contribute to disulfide bonding. Each HB-EGF disulfide analogue (HB-EGF-Cys/Ser108/121, HB-EGF-Cys/Ser116/132, and HB-EGF-Cys/Ser134/143) was cloned under the regulation of the mouse metallothionein (MT) promoter and stably expressed in mouse fibroblasts. HB-EGF immunoreactive proteins with Mr of 6.5, 21 and 24kDa were observed from lys...

  16. Historia y globalización. VIII Conversaciones Internacionales de Historia [Reseña


    Olábarri-Gortázar, I. (Ignacio)


    Reseña de Francisco Javier Caspistegui (ed.), Historia y globalización. VIII Conversaciones Internacionales de Historia. Universidad de Navarra. Pamplona, 7-9 de octubre de 2010, Pamplona, EUNSA, 2012. 318 pp. ISBN: 9788431328801.


    Directory of Open Access Journals (Sweden)

    Barbara Faganel


    Full Text Available Background. The inhibitors to F VIII are unusual in case of a mild haemophilia because the replacement therapy is seldom necessary. In case of severe trauma, when prolonged replacement therapy of F VIII is needed, the appearance of the inhibitors is more frequent. The mild form of the disease becomes a severe one and the haemorrhages are frequent.Patient and methods. In case of our patient with mild form of haemophilia, the inhibitors to F VIII developed after prolonged replacement therapy for treatement of subdural haemorrhage. In the article we describe recurrent haemorrhages and treatement of them with FEIBA and rF VIIa.Conclusions. Due to poor compliance of an elder patient we didn’t decide to treat the inhibitors for F VIII actively.

  18. Expression Profiles, Characterization and Function of HbTCTP in Rubber Tree (Hevea brasiliensis). (United States)

    Deng, Zhi; Chen, Jiangshu; Leclercq, Julie; Zhou, Zhuangzhi; Liu, Changren; Liu, Hui; Yang, Hong; Montoro, Pascal; Xia, Zhihui; Li, Dejun


    As a highly conserved protein, the translationally controlled tumor protein (TCTP) carries out vital roles in various life processes. In rubber tree, two TCTP genes, HbTCTP and HbTCTP1, were cloned, but only HbTCTP1 was studied in details. In this study, cis-acting regulatory elements, expression patterns, subcellular localization, interacting proteins, and antioxidant activity of HbTCTP were systematically analyzed. Besides the common cis-acting regulatory elements, HbTCTP promoter also harbored various known cis-elements that respond to hormone/stresses. Being consistent with the aforementioned results, HbTCTP was regulated by drought, low temperature, high salt, ethylene (ET), wounding, H2O2, and methyl jasmonate (MeJA) treatments. HbTCTP was expressed throughout different tissues and developmental stages of leaves. In addition, HbTCTP was associated with tapping panel dryness (TPD). HbTCTP was localized in the membrane, cytoplasm and the nucleus, and interacted with four proteins rubber elongation factor (REF), 17.5 kDa heat shock family protein, annexin, and REF-like stress related protein 1. Being similar to HbTCTP1, HbTCTP also indicated antioxidant activity in metal-catalyzed oxidation (MCO) system. Our results are useful for further understanding the molecular characterization and expression profiles of HbTCTP, but also lay a solid foundation for elucidating the function of HbTCTP in rubber tree.

  19. Cell model for the study of receptor and regulatory functions of human proHB-EGF

    Directory of Open Access Journals (Sweden)

    N. V. Korotkevych


    Full Text Available Developing of new models and approaches, particularly with fluorescent techniques, for investigation of intracellular transport of proHB-EGF and its ligand-receptor complexes is strongly required. In order to create a model for studying proHB-EGF functions the genetic construction pEGFP-N1-proHB-EGF, encoding proHB-EGF-EGFP which is fluorescent-labeled form of proHB-EGF with enhanced green fluorescent protein EGFP in the cytoplasmic terminus of the molecule, was obtained. Eukaryotic cells expressing fusion protein proHB-EGF-EGFP on the cell surface were obtained by transfection with pEGFP-N1-proHB-EGF. Expressed in the Vero cells proHB-EGF-EGFP could bind fluorescent derivative of nontoxic receptor-binding subunit B of diphtheria toxin mCherry-SubB. After stimulation of transfected cells with TPA (12-O-Tetradecanoylphorbol-13-acetate, proHB-EGF-EGFP formed a fluorescentl-labeled C-terminal fragment of the molecule – CTF-EGFP. Thus, the obtained genetic construction pEGFP-N1-proHB-EGF could be helpful in visualization of molecules proHB-EGF and CTF in cells, may open new possibilities for the studying of their functions, such as receptor function of proHB-EGF for diphtheria toxin, intracellular translocation of CTF and provide possibilities for natural proHB-EGF ligands search.

  20. [Cell model for the study of receptor and regulatory functions of human proHB-EGF]. (United States)

    Korotkevych, N V; Labyntsev, A Iu; Manoĭlov, K Iu; Krynina, O I; Diachenko, K V; Kolybo, D V; Komisarenko, S V


    Developing of new models and approaches, particularly with fluorescent techniques, for investigation of intracellular transport of proHB-EGF and its ligand-receptor complexes is strongly required. In order to create a model for studying proHB-EGF functions the genetic construction pEGFP-N1-proHB-EGF, encoding proHB-EGF-EGFP which is fluorescent-labeled form of proHB-EGF with enhanced green fluorescent protein EGFP in the cytoplasmic terminus of the molecule, was obtained. Eukaryotic cells expressing fusion protein proHB-EGF-EGFP on the cell surface were obtained by transfection with pEGFP-N1-proHB-EGF. Expressed in the Vero cells proHB-EGF-EGFP could bind fluorescent derivative of nontoxic receptor-binding subunit B of diphtheria toxin mCherry-SubB. After stimulation oftransfected cells with TPA (12-O-Tet-radecanoylphorbol-13-acetate), proHB-EGF-EGFP formed a fluorescentl-labeled C-terminal fragment of the molecule - CTF-EGFP. Thus, the obtained genetic construction pEGFP-N1-proHB-EGF could be helpful in visualization of molecules proHB-EGF and CTF in cells, may open new possibilities for the studying of their functions, such as receptor function of proHB-EGF for diphtheria toxin, intracellular translocation of CTF and provide possibilities for natural proHB-EGF ligands search.

  1. Rare hemoglobin variants: Hb G-Szuhu (HBB: c.243C>G), Hb G-Coushatta (HBB: c.68A>C) and Hb Mizuho (HBB: c.206T>C) in Sri Lankan families. (United States)

    Perera, P Shiromi; Silva, Ishari; Hapugoda, Menaka; Wickramarathne, Merita N; Wijesiriwardena, Indira; Efremov, Dimitar G; Fisher, Christopher A; Weatherall, David J; Premawardhena, Anuja


    In this short communication, we describe the clinical presentation of unusual hemoglobin (Hb), variants in three Sri Lankan cases under study for β-thalassemia intermedia (β-TI). We believe this is the first report on their occurrence in Sri Lanka as well as from the Indian subcontinent. During a molecular study performed on β-TI patients, we identified three unusual Hb variants as Hb G-Szuhu (HBB: c.243C>G), Hb G-Coushatta (HBB: c.68A>C) and Hb Mizuho (HBB: c.206T>C) in three unrelated families. Hb G-Szuhu and Hb G-Coushatta were found in combination with the common β-thalassemia (β-thal) mutation, IVS-I-5 (G>C). Both probands had mild anemia with greatly reduced red cell indices and had non palpable livers and spleens, however, by ultrasound, both were observed to be enlarged. The final Hb variant, Hb Mizuho, was identified as a heterozygous mutation found in both proband and his mother. Both family members had severe anemia and were regularly transfused and had increased red cell parameters.

  2. A Cranial Trauma was the Cause of Death of Charles VIII of France (1470-1498). (United States)

    Markatos, Konstantinos; Karamanou, Marianna; Arkoudi, Konstantina; Konstantinidi, Apostolia; Androutsos, Georgios


    This article summarizes the reign, life and death, of Charles VIII of France. Also we intend to investigate current views on his cause of death, contradictions and opinions of his biographers. Poisoning, disease, and injury are the possible causes of his death but, according to the literature, cranial trauma was the most probable cause of death of the King Charles VIII of France. Copyright © 2017 Elsevier Inc. All rights reserved.



    sudyastuti sudyastuti; heru mugiarso


    This research was conducted based on the phenomenon that happens to grade VIII SMPIT Bina Amal Semarang which has the social conformity low. The purpose of this research is to proof  the influence of counseling service groups towards the conformity. The type of this research is experimental research. The research was conducted with seven times the grant of preferential treatment on grade VIII SMPIT Bina Amal Semarang, research subject with 8 students. The data collection method used is the ps...

  4. Type VIII collagen has a restricted distribution in specialized extracellular matrices



    A pepsin-resistant triple helical domain (chain 50,000 Mr) of type VIII collagen was isolated from bovine corneal Descemet's membrane and used as an immunogen for the production of mAbs. An antibody was selected for biochemical and tissue immunofluorescence studies which reacted both with Descemet's membrane and with type VIII collagen 50,000-Mr polypeptides by competition ELISA and immunoblotting. This antibody exhibited no crossreactivity with collagen types I-VI by competition ELISA. The m...

  5. Complex structure of the supernova remnant HB 3 (United States)

    Leahy, D. A.; Venkatesan, D.; Long, K. S.; Naranan, S.


    HB 3 is an old, large (84 pc diameter) supernova remnant associated with the W3 H II region/molecular cloud complex. Observations of the imaging proportional counter (IPC) onboard the Einstein X-ray astronomy satellite have been reprocessed to yield a contour map of X-ray brightness and spectra of various regions of this remnant. The measured IPC flux is 2.4 x 10 to the -11th ergs per sq cm per s, giving a 0.2-4 keV luminosity of 1.6 x 10 to the 35th ergs/s for a column densityof 6 x 10 to the 21st per sq cm. The measured X-ray temperatures reveal a decrease from center to limb of the remnant of 1-0.3 keV. HB 3 is in the late adiabatic blast-wave phase of evolution, 30,000 to 50,000 yr old and with an initial blast energy of 3 x 10 to the 50th ergs. The X-ray map is compared with available radio and optical images. In X-rays, HB 3 has two components - a diffuse emission inside the 84 pc radio remnant and a ring of emission at the center of 30 pc in diameter. The diffuse emission is similar to that from other supernova remnants which are moderately obscured (column density, nH approximately 10 to the 22nd per sq cm). Three possibilities for the origin of the ring are explored: (1) a second supernova remnant, (2) a shocked shell in the interstellar medium surrounding HB 3, and (3) reverse-shock heated ejecta. There is no hot neutron star within the remnant.

  6. Glutathione Redox System in β-Thalassemia/Hb E Patients

    Directory of Open Access Journals (Sweden)

    Ruchaneekorn W. Kalpravidh


    Full Text Available β-thalassemia/Hb E is known to cause oxidative stress induced by iron overload. The glutathione system is the major endogenous antioxidant that protects animal cells from oxidative damage. This study aimed to determine the effect of disease state and splenectomy on redox status expressed by whole blood glutathione (GSH/glutathione disulfide (GSSG and also to evaluate glutathione-related responses to oxidation in β-thalassemia/Hb E patients. Twenty-seven normal subjects and 25 β-thalassemia/Hb E patients were recruited and blood was collected. The GSH/GSSG ratio, activities of glutathione-related enzymes, hematological parameters, and serum ferritin levels were determined in individuals. Patients had high iron-induced oxidative stress, shown as significantly increased serum ferritin, a decreased GSH/GSSG ratio, and increased activities of glutathione-related enzymes. Splenectomy increased serum ferritin levels and decreased GSH levels concomitant with unchanged glutathione-related enzyme activities. The redox ratio had a positive correlation with hemoglobin levels and negative correlation with levels of serum ferritin. The glutathione system may be the body’s first-line defense used against oxidative stress and to maintain redox homeostasis in thalassemic patients based on the significant correlations between the GSH/GSSH ratio and degree of anemia or body iron stores.

  7. Implications of an updated ultraviolet background for the ionization mechanisms of intervening Ne VIII absorbers (United States)

    Hussain, Tanvir; Khaire, Vikram; Srianand, Raghunathan; Muzahid, Sowgat; Pathak, Amit


    Ne VIII absorbers seen in QSO spectra are useful tracers of warm ionized gas, when collisional ionization is the dominant ionization process. While photoionization by the ultraviolet background (UVB) is a viable option, it tends to predict large line-of-sight thickness for the absorbing gas. Here, we study the implications of the recently updated UVB at low z to understand the ionization mechanisms of intervening Ne VIII absorbers. With the updated UVB, one typically needs higher density and metallicity to reproduce the observed ionic column densities under photoionization. Both reduce the inferred line-of-sight thicknesses of the absorbers. We find a critical density of ≥5 × 10-5 cm-3 above which the observed N({Ne VIII})/N({O VI}) can be reproduced by pure collisional processes. If the gas is of near solar metallicity (as measured for the low ions) then the cooling time-scales will be small (inferred low ion metallicity is near solar or supersolar. If we assume the Ne VIII phase to have similar metallicities then photoionization can reproduce the observed N({Ne VIII})/N({O VI}) without the line-of-sight thickness being unreasonably large and avoids cooling issues related to the collisional ionization at these metallicities. However, the indication of broad Lyα absorption in a couple of systems, if true, suggests that the Ne VIII phase is distinct from the low ion phase having much lower metallicity.

  8. Functional mapping of factor VIII C2 domain. (United States)

    Pellequer, Jean-Luc; Chen, Shu-wen W; Saboulard, Didier; Delcourt, Marc; Négrier, Claude; Plantier, Jean-Luc


    The factor VIII (FVIII) is a cofactor of the coagulation cascade. The FVIII C2 domain is a critical domain that participates in the interactions with the von Willebrand factor and the phospholipidic surfaces. To assess the importance of each residue of this domain in the maintenance of the structure and the function of FVIII, a number (n=139) of mutants were generated by substituting the original residues, from Ser2173 to Gly2325, by an alanine. Mutants were built within a complete B domain-deleted FVIII and expressed in COS-1 cells. Mutant antigen levels and procoagulant activities were measured. Two in silico analyses, a sliding average procedure and an analysis of the mutation energy cost were conducted in parallel on the FVIII structure. Both results were in agreement with the functional data, and illustrated the benefit of using such strategies prior to targeting specific residues in the aim of generating active recombinant molecules. The functional assays identify the residues that are important to maintaining the structure of the C2 domain, mainly those forming β-sheet, and those that can afford substitution, establishing a detailed functional relation with the available crystallographic data. This study provided a comprehensive functional mapping of the FVIII C2 domain and discussed the implication of specific residues in respect to the maintenance in the activity and structure stability, the efficiency in secretion, the binding to phospholipids and the formation of epitope.

  9. piggyBac-mediated phenotypic correction of factor VIII deficiency

    Directory of Open Access Journals (Sweden)

    Janice M Staber


    Full Text Available Hemophilia A, caused by a deficiency in factor VIII (FVIII, is the most severe inherited bleeding disorder. Hemophilia A is an attractive gene therapy candidate because even small increases in FVIII levels will positively alter the phenotype. While several vectors are under investigation, gene addition from an integrated transgene offers the possibility of long term expression. We engineered the DNA transposon-based vector, piggyBac (PB, to carry a codon-optimized B-domain deleted human FVIII cDNA. Evaluation of gene transfer efficiency in FVIII null mice demonstrated that PB containing the FVIII cDNA, delivered via hydrodynamic injection to immunocompetent hemophilia mice, conferred persistent gene expression, attaining mean FVIII activity of approximately 60% with 3/19 developing inhibitors. In addition to efficacious expression, a goal of gene transfer-based therapies is to develop vectors with low toxicity. To assess endoplasmic reticulum stress in hepatocytes stably expressing the transgene, we evaluated levels of ER stress markers via qPCR and found no evidence of cell stress. To evaluate phenotypic correction, a tail clip assay performed at the end of the study revealed reduced blood loss. These data demonstrate that PB can be used to achieve sustained FVIII expression and long-term therapeutic benefit in a mouse model.

  10. Inhibition of Hb Binding to GP1bα Abrogates Hb-Mediated Thrombus Formation on Immobilized VWF and Collagen under Physiological Shear Stress. (United States)

    Annarapu, Gowtham K; Singhal, Rashi; Peng, Yuandong; Guchhait, Prasenjit


    Reports including our own describe that intravascular hemolysis increases the risk of thrombosis in hemolytic disorders. Our recent study shows that plasma Hb concentrations correlate directly with platelet activation in patients with paroxysmal nocturnal hemoglobinuria (PNH). The binding of Hb to glycoprotein1bα (GP1bα) increases platelet activation. A peptide AA1-50, designed from N-terminal amino acid sequence of GP1bα significantly inhibits the Hb binding to GP1bα as well as Hb-induced platelet activation. This study further examined if the Hb-mediated platelet activation plays any significant role in thrombus formation on subendothelium matrix under physiological flow shear stresses and the inhibition of Hb-platelet interaction can abrogate the above effects of Hb. Study performed thrombus formation assay in vitro by perfusing whole blood over immobilized VWF or collagen type I in presence of Hb under shear stresses simulating arterial or venous flow. The Hb concentrations ranging from 5 to 10 μM, commonly observed level in plasma of the hemolytic patients including PNH, dose-dependently increased thrombus formation on immobilized VWF under higher shear stress of 25 dyne/cm2, but not at 5 dyne/cm2. The above Hb concentrations also increased thrombus formation on immobilized collagen under both shear stresses of 5 and 25 dyne/cm2. The peptide AA1-50 abrogated invariably the above effects of Hb on thrombus formation. This study therefore indicates that the Hb-induced platelet activation plays a crucial role in thrombus formation on immobilized VWF or collagen under physiological flow shear stresses. Thus suggesting a probable role of this mechanism in facilitating thrombosis under hemolytic conditions.

  11. Hb Papanui [α99(G8)Lys→Arg; HBA2: c.299A>G]: a novel silent substitution interfering in Hb A1c determination. (United States)

    Brennan, Stephen O; Chan, Tim


    We report a novel hemoglobin (Hb) mutation [Hb Papanui [α99(G8)Lys→Arg; HBA2: c.299A>G] that was identified in an individual with an inappropriately low Hb A1c value of 2.8% when using an ion exchange method. Although occurring at a well conserved site, the conservative substitution was not associated with any adverse clinical features.

  12. The Long and Winding Road to Optimal HbA1c Measurement (United States)

    Little, Randie R.; Rohlfing, Curt


    The importance of hemoglobin A1c (HbA1c) as an indicator of mean glycemia and risks for complications in patients with diabetes mellitus was established by the results of long-term clinical trials, most notably the Diabetes Control and Complications Trial (DCCT) and United Kingdom Prospective Diabetes Study (UKPDS), published in 1993 and 1998 respectively. However, clinical application of recommended HbA1c targets that were based on these studies was difficult due to lack of comparability of HbA1c results among assay methods and laboratories. Thus, the National Glycohemoglobin Standardization Program (NGSP) was initiated in 1996 with the goal of standardizing HbA1c results to those of the DCCT/UKPDS. HbA1c standardization efforts have been highly successful; however, a number of issues have emerged on the “long and winding road” to better HbA1c, including the development of a higher-order HbA1c reference method by the International Federation of Clinical Chemistry (IFCC), recommendations to use HbA1c to diagnose as well as monitor diabetes, and point-of-care (POC) HbA1c testing. Here, we review the past, present and future of HbA1c standardization and describe the current status of HbA1c testing, including limitations that healthcare providers need to be aware of when interpreting HbA1c results. PMID:23318564

  13. A patient with hyperglycaemia and normal HbA Ic due to impaired glycation

    NARCIS (Netherlands)

    Diekman, M. J. M.; Salden, H. J. M.; DeVries, J. H.


    A diabetic Caucasian woman presented with discrepantly low HbA Ic values compared with her glycaemia. High-performance liquid chromatography (HPLC) analysis disclosed 80% HbA and 20% HbI Philadelphia (I6alpha2 lys --> glut). The calculated glycosylation gap from the fructosamine level was 1.2%. The

  14. Nuclear translocation of the cytoplasmic domain of HB-EGF induces gastric cancer invasion (United States)


    Background Membrane-anchored heparin-binding epidermal growth factor-like growth factor (proHB-EGF) yields soluble HB-EGF, which is an epidermal growth factor receptor (EGFR) ligand, and a carboxy-terminal fragment of HB-EGF (HB-EGF-CTF) after ectodomain shedding. We previously reported that HB-EGF-CTF and unshed proHB-EGF which has the cytoplasmic domain of proHB-EGF (HB-EGF-C), translocate from the plasma membrane to the nucleus and regulate cell cycle after shedding stimuli. However, the significance of nuclear exported HB-EGF-C in human gastric cancer is unclear. Methods We investigated the relationship between intracellular localization of HB-EGF-C and clinical outcome in 96 gastric cancer patients treated with gastrectomy. Moreover, we established stable gastric cancer cell lines overexpressing wild-type HB-EGF (wt-HB-EGF) and mutated HB-EGF (HB-EGF-mC), which prevented HB-EGF-C nuclear translocation after shedding. Cell motility between these 2 gastric cancer cell lines was investigated using a transwell invasion assay and a wound healing assay. Results Of the 96 gastric cancer cases, HB-EGF-C immunoreactivity was detected in both the nucleus and cytoplasm in 19 cases (19.8 %) and in the cytoplasm only in 25 cases (26.0 %). The nuclear immunoreactivity of HB-EGF-C was significantly increased in stage pT3/4 tumors compared with pT1/2 tumors (T1/2 vs. T3/4: 11.1 % vs. 36.4 %, P HB-EGF- and HB-EGF-mC-expressing cells significantly increased compared with control cells, but the growth of HB-EGF-mC-expressing cells was significantly decreased compared with wt-HB-EGF-expressing cells. Gastric cancer cell invasion obviously increased in wt-HB-EGF-expressing cells, but invasion in HB-EGF-mC-expressing cells showed a slight increase compared with control cells. Moreover, wt-HB-EGF overexpression increased the effectiveness of wound healing, but had no significant effect in HB-EGF-mC-expressing cells. Conclusions Both the function of HB-EGF as an EGFR ligand

  15. Factor VIII and fibrinogen recovery in plasma after Theraflex methylene blue-treatment: effect of plasma source and treatment time. (United States)

    Rapaille, André; Reichenberg, Stefan; Najdovski, Tome; Cellier, Nicolas; de Valensart, Nicolas; Deneys, Véronique


    The quality of fresh-frozen plasma is affected by different factors. Factor VIII is sensitive to blood component storage processes and storage as well as pathogen-reduction technologies. The level of fibrinogen in plasma is not affected by the collection processes but it is affected by preparation and pathogen-reduction technologies. The quality of plasma from whole blood and apheresis donations harvested at different times and treated with a pathogen-reduction technique, methylene blue/light, was investigated, considering, in particular, fibrinogen and factor VIII levels and recovery. The mean factor VIII level after methylene blue treatment exceeded 0.5 IU/mL in all series. Factor VIII recovery varied between 78% and 89% in different series. The recovery of factor VIII was dependent on plasma source as opposed to treatment time. The interaction between the two factors was statistically significant. Mean levels of fibrinogen after methylene blue/light treatment exceeded 200 mg/dL in all arms. The level of fibrinogen after treatment correlated strongly with the level before treatment. There was a negative correlation between fibrinogen level before treatment and recovery. Pearson's correlation coefficient between factor VIII recovery and fibrinogen recovery was 0.58. These results show a difference in recovery of factor VIII and fibrinogen correlated with plasma source. The recovery of both factor VIII and fibrinogen was higher in whole blood plasma than in apheresis plasma. Factor VIII and fibrinogen recovery did not appear to be correlated.

  16. Potentiation of thrombin generation in hemophilia A plasma by coagulation factor VIII and characterization of antibody-specific inhibition.

    Directory of Open Access Journals (Sweden)

    Bhavya S Doshi

    Full Text Available Development of inhibitory antibodies to coagulation factor VIII (fVIII is the primary obstacle to the treatment of hemophilia A in the developed world. This adverse reaction occurs in 20-30% of persons with severe hemophilia A treated with fVIII-replacement products and is characterized by the development of a humoral and neutralizing immune response to fVIII. Patients with inhibitory anti-fVIII antibodies are treated with bypassing agents including recombinant factor VIIa (rfVIIa. However, some patients display poor hemostatic response to bypass therapy and improved treatment options are needed. Recently, we demonstrated that fVIII inhibitors display widely variable kinetics of inhibition that correlate with their respective target epitopes. Thus, it was hypothesized that for antibodies that display slow rates of inhibition, supplementation of rfVIIa with fVIII would result in improved thrombin generation and be predictive of clinical responses to this novel treatment regimen. In order to test this hypothesis, 10 murine monoclonal antibodies (MAbs with non-overlapping epitopes spanning fVIII, differential inhibition titers, and inhibition kinetics were studied using a thrombin generation assay. Of the 3 MAbs with high inhibitory titers, only the one with fast and complete (classically defined as "type I" kinetics displayed significant inhibition of thrombin generation with no improvement upon supplementation of rfVIIa with fVIII. The other two MAbs that displayed incomplete (classically defined as "type II" inhibition did not suppress the potentiation of thrombin generation by fVIII. All antibodies that did not completely inhibit fVIII activity demonstrated potentiation of thrombin generation by the addition of fVIII as compared to rfVIIa alone. In conclusion, fVIII alone or in combination with rfVIIa corrects the thrombin generation defect produced by the majority of anti-fVIII MAbs better than single agent rfVIIa. Therefore, combined fVIII

  17. The History of GalaFLEX P4HB Scaffold


    Williams, Simon F.; Martin, David P.; Moses, Arikha C.


    The GalaFLEX Scaffold (Galatea Surgical, Inc., Lexington, MA) for plastic and reconstructive surgery belongs to a new generation of products for soft tissue reinforcement made from poly-4-hydroxybutyrate (P4HB). Other members of this new family of products include MonoMax Suture (Aesculap AG, Tuttlingen, Germany) for soft tissue approximation, BioFiber Scaffold (Tornier, Inc., Edina, MN) for tendon repair, and Phasix Mesh (C.R. Bard, Inc., Murray Hill, NJ) for hernia repair. Each of these ful...

  18. Coinheritance of Hb D-Punjab and β-thalassemia: diagnosis and implications in prenatal diagnosis. (United States)

    Das, Sheila; Mashon, Ranjeet S


    Hb D-Punjab (HBB: c.364G>C) is an abnormal hemoglobin (Hb) associated with genetic risk in association with Hb S (HBB: c.20A>T). In addition, misdiagnosing homozygosis for hemizygosis may have implication for genetic risk assessment. We present the diagnostic utility of high performance liquid chromatography (HPLC) in differential diagnosis between the Hb D-Punjab homozygote and the Hb D-Punjab/β-thalassemia (β-thal) genotype. The Hb A2 level measurement may not be a reliable parameter to differentiate between the two conditions. In a screening program for risk prediction, the genotype should be confirmed by family study and/or molecular analysis. Misdiagnosis can have potentially adverse implications in a prenatal diagnosis (PND) program, particularly in areas where consanguinity is common and this Hb D-Punjab variant occurs.

  19. Recombinant factor VIII in the management of hemophilia A: current use and future promise

    Directory of Open Access Journals (Sweden)

    Jerry S Powell


    Full Text Available Jerry S PowellDivision of Hematology and Oncology, University of California Davis Cancer Center, Sacramento, CA, USAAbstract: Hemophilia A is a rare inherited bleeding disorder due to mutation of the gene that encodes the coagulation protein factor VIII. Historically, prior to the availability of treatment with factor VIII preparations, most boys died from uncontrolled bleeding, either spontaneous bleeding or after injury, before reaching 20 years of age. One of the most impressive triumphs of modern medicine is that with current recombinant factor VIII replacement therapy, a boy born in the 21st century with severe hemophilia A can anticipate a normal life expectancy with essentially no permanent complications from bleeding. For severe hemophilia A, current optimal treatment should have two goals: first, to provide sufficient factor VIII to prevent spontaneous bleeding, and second, to provide sufficient factor VIII to have normal coagulation function after any trauma. However, the replacement therapy requires tremendous resources for effective use, and remains extraordinarily expensive. Thus there are opportunities for further advances in therapy for hemophilia A. Two major concerns continue to trouble current optimal treatment approaches: some patients will develop neutralizing antibodies during the first 50 infusions of therapeutic factor VIII, and second, to administer therapeutic factor VIII every other day in young boys often requires placement of a central venous access device, and such use carries the life-threatening risks of infection and thrombosis. Because of the effectiveness of current therapy, any new developments in treatment will require significant concerns for safety, both immediate and in the long term. A number of research groups seek to prolong the biological efficacy of infused recombinant factor VIII. Currently, one such promising development is in the advanced stages of clinical trial. The goals will be to improve

  20. The F309S mutation increases factor VIII secretion in human cell line

    Directory of Open Access Journals (Sweden)

    Daianne Maciely Carvalho Fantacini


    Full Text Available ABSTRACT OBJECTIVES: The capacity of a human cell line to secrete recombinant factor VIII with a F309S point mutation was investigated, as was the effect of the addition of chemical chaperones (betaine and sodium-4-phenylbutyrate on the secretion of factor VIII. METHODS: This work used a vector with a F309S mutation in the A1 domain to investigate FVIII production in the HEK 293 human cell line. Factor VIII activity was measured by chromogenic assay. Furthermore, the effects of chemical drugs on the culture were evaluated. RESULTS: The addition of the F309S mutation to a previously described FVIII variant increased FVIII secretion by 4.5 fold. Moreover, the addition of betaine or sodium-4-phenylbutyrate increased the secretion rate of FVIIIΔB proteins in HEK 293 cells, but the same effect was not seen for FVIIIΔB-F309S indicating that all the recombinant protein produced had been efficiently secreted. CONCLUSION: Bioengineering factor VIII expressed in human cells may lead to an efficient production of recombinant factor VIII and contribute toward low-cost coagulation factor replacement therapy for hemophilia A. FVIII-F309S produced in human cells can be effective in vivo.

  1. Desenvolvimento de inibidores do fator VIII na hemofilia A Development of factor VIII inhibitors in hemophilia A

    Directory of Open Access Journals (Sweden)

    Daniel G. Chaves


    Full Text Available A hemofilia A é uma coagulopatia genética com herança recessiva ligada ao cromossomo X que afeta 1-2 a cada 10 mil indivíduos do sexo masculino nascidos vivos. Estes indivíduos têm baixas concentrações ou ausência do fator VIII (FVIII da coagulação no plasma e apresentam quadros hemorrágicos leves, moderados e graves, dependendo da atividade de FVIII circulante. Estes pacientes necessitam de constante reposição proteica e aproximadamente 30% deles desenvolvem aloanticorpos contra a proteína exógena. A síntese dos anticorpos anti-FVIII é iniciada quando o FVIII exógeno é endocitado por células apresentadoras de antígeno, degradado e apresentado às células T CD4+ na forma de peptídeos ligados a moléculas do complexo maior de histocompatibilidade (MHC de classe II. Alguns fatores de risco (paciente/tratamento podem ser relacionados ao desenvolvimento desta resposta imune. Neste contexto, as mutações no gene do FVIII e polimorfismos em genes envolvidos na resposta imune são candidatos moleculares como determinantes imunogenéticos na predisposição para o desenvolvimento de inibidores. Por não ser completamente entendido e controlado, o desenvolvimento desta resposta imune contra o FVIII constitui o maior problema decorrente do tratamento de indivíduos portadores de hemofilia A e faz-se necessária busca de opções que visem minimizar suas ações deletérias. Algumas alternativas de tratamento têm se mostrado eficazes no tratamento (anti-CD20, plasmaférese, concentrado de complexo protrombínico (PCCs, concentrado de complexo protrombínico ativado (APCCs, fator VII humano ativado, mas a retirada ou neutralização específica dos inibidores de FVIII ainda não foram alcançadas.Hemophilia A, which affects 1-2:10,000 live-born male neonates, is a genetic coagulopathy with recessive inheritance linked to the X chromosome. These individuals have low concentrations or no coagulation factor VIII (FVIII in the plasma

  2. Relationship of HbA1c variability, absolute changes in HbA1c, and all-cause mortality in type 2 diabetes

    DEFF Research Database (Denmark)

    Skriver, Mette Vinther; Sandbæk, Annelli; Kristensen, Jette Kolding


    OBJECTIVE: We assessed the relationship of mortality with glycated hemoglobin (HbA1c) variability and with absolute change in HbA1c. DESIGN: A population-based prospective observational study with a median follow-up time of 6 years. METHODS: Based on a validated algorithm, 11 205 Danish individuals...... with type 2 diabetes during 2001-2006 were identified from public data files, with at least three HbA1c measurements: one index measure, one closing measure 22-26 months later, and one measurement in-between. Medium index HbA1c was 7.3%, median age was 63.9 years, and 48% were women. HbA1c variability...

  3. Generation of an optimized lentiviral vector encoding a high-expression factor VIII transgene for gene therapy of hemophilia A. (United States)

    Johnston, J M; Denning, G; Doering, C B; Spencer, H T


    We previously compared the expression of several human factor VIII (fVIII) transgene variants and demonstrated the superior expression properties of B domain-deleted porcine fVIII. Subsequently, a hybrid human/porcine fVIII molecule (HP-fVIII) comprising 91% human amino-acid sequence was engineered to maintain the high-expression characteristics of porcine fVIII. The bioengineered construct then was used effectively to treat knockout mice with hemophilia A. In the current study, we focused on optimizing self-inactivating (SIN) lentiviral vector systems by analyzing the efficacy of various lentiviral components in terms of virus production, transduction efficiency and transgene expression. Specifically, three parameters were evaluated: (1) the woodchuck hepatitis post-transcriptional regulatory element (WPRE), (2) HIV versus SIV viral vector systems and (3) various internal promoters. The inclusion of a WPRE sequence had negligible effects on viral production and HP-fVIII expression. HIV and SIV vectors were compared and found to be similar with respect to transduction efficiency in both K562s and HEK-293T cells. However, there was an enhanced expression of HP-fVIII by the SIV system, which was evident in both K562 and BHK-M cell lines. To further compare expression of HP-fVIII from an SIV-based lentiviral system, we constructed expression vectors containing the high expression transgene and a human elongation factor-1 alpha, cytomegalovirus (CMV) or phosphoglycerate kinase promoter. Expression was significantly greater from the CMV promoter, which also yielded therapeutic levels of HP-fVIII in hemophilia A mice. Based on these studies, an optimized vector contains the HP-fVIII transgene driven by a CMV internal promoter within a SIV-based lentiviral backbone lacking a WPRE.

  4. Expression of Heparin-Binding EGF-Like Growth Factor (HB-EGF) in Bovine Endometrium: Effects of HB-EGF and Interferon-τ on Prostaglandin Production. (United States)

    Takatsu, K; Acosta, T J


    Heparin-binding EGF-like growth factor (HB-EGF) regulates several cell functions by binding to its membrane receptor (ErbB1 and ErbB4). Experimental evidences suggest that HB-EGF, prostaglandins (PGs) and interferon-τ (IFN-τ) regulate uterine function for pregnancy establishment in ruminants. In this study, the mRNA expressions of HB-EGF, ErbB1 and ErbB4 in bovine endometrium and the effects of HB-EGF and IFN-τ on PGE2 and PGF2-α production by endometrial cells were investigated. RT-PCR analysis revealed that HB-EGF mRNA was greater at the mid-luteal stage than at the early and regressed luteal stages (p HB-EGF, ErbB1 and ErbB4 mRNA in epithelial cells (p HB-EGF did not affect PGF2-α or PGE2 production by bovine endometrial epithelial cells, but increased PGF2-α and PGE2 production by bovine endometrial stromal cells (p HB-EGF-stimulated PGF2-α (p  0.05) production by stromal cells. These results indicate that HB-EGF and its receptors expression changed in bovine endometrium throughout the oestrous cycle. IFN-τ increased their expression in cultured endometrial cells. HB-EGF and IFN-τ have the ability to regulate PGs production by stromal cells and therefore may play a role in the local regulation of uterine function at the time of implantation in cattle. © 2015 Blackwell Verlag GmbH.

  5. Endogenous PttHb1 and PttTrHb, and heterologous Vitreoscilla vhb haemoglobin gene expression in hybrid aspen roots with ectomycorrhizal interaction. (United States)

    Jokipii, Soile; Häggman, Hely; Brader, Günter; Kallio, Pauli T; Niemi, Karoliina


    Present knowledge on plant non-symbiotic class-1 (Hb1) and truncated (TrHb) haemoglobin genes is almost entirely based on herbaceous species while the corresponding tree haemoglobin genes are not well known. The function of these genes has recently been linked with endosymbioses between plants and microbes. In this work, the coding sequences of hybrid aspen (Populus tremulaxtremuloides) PttHb1 and PttTrHb were characterized, indicating that the key residues of haem and ligand binding of both genes were conserved in the deduced amino acid sequences. The expression of PttHb1 and PttTrHb was examined in parallel with that of the heterologous Vitreoscilla haemoglobin gene (vhb) during ectomycorrhiza/ectomycorrhizal (ECM) interaction. Both ECM fungi studied, Leccinum populinum and Xerocomus subtomentosus, enhanced root formation and subsequent growth of roots of all hybrid aspen lines, but only L. populinum was able to form mycorrhizas. Real-time PCR results show that the dual culture with the ECM fungus, with or without emergence of symbiotic structures, increased the expression of both PttHb1 and PttTrHb in the roots of non-transgenic hybrid aspens. PttHb1 and PttTrHb had expression peaks 5 h and 2 d after inoculation, respectively, pointing to different functions for these genes during interaction with root growth-improving fungi. In contrast, ECM fungi were not able to enhance the expression of hybrid aspen endogenous haemoglobin genes in the VHb lines, which may be a consequence of the compensating action of heterologous haemoglobin.

  6. Hemodialysis in a patient with severe hemophilia A and factor VIII inhibitor. (United States)

    Gopalakrishnan, Natarajan; Usha, Thiruvengadam; Thopalan, Balasubramaniyan; Dhanapriya, Jeyachandran; Dineshkumar, Thanigachalam; Thirumalvalavan, Kaliaperumal; Sakthirajan, Ramanathan


    Hemophilia A is a hereditary X-linked recessive disease caused by mutations in the gene encoding factor VIII (FVIII), occurring in 1 out of 10,000 persons. Life expectancy and quality of life have dramatically improved recently in patients with hemophilia. Chronic kidney disease and need for renal replacement therapy in these patients are rare. The development of inhibitors to FVIII is the most serious complication of hemophilia and makes treatment of bleeds very challenging. We describe here a 28-year-old male patient with severe hemophilia A with presence of factor VIII inhibitor, who had end stage renal disease. Central venous access device was inserted along with infusion of factor eight inhibitor bypass activity before and after the procedure. He is currently on thrice weekly hemodialysis and doing well for 6 months without bleeding episodes. To our knowledge, hemophilia A with factor VIII inhibitor managed with hemodialysis has not been reported so far. © 2016 International Society for Hemodialysis.

  7. Identification of a Chemical Probe for Family VIII Bromodomains through Optimization of a Fragment Hit. (United States)

    Gerstenberger, Brian S; Trzupek, John D; Tallant, Cynthia; Fedorov, Oleg; Filippakopoulos, Panagis; Brennan, Paul E; Fedele, Vita; Martin, Sarah; Picaud, Sarah; Rogers, Catherine; Parikh, Mihir; Taylor, Alexandria; Samas, Brian; O'Mahony, Alison; Berg, Ellen; Pallares, Gabriel; Torrey, Adam D; Treiber, Daniel K; Samardjiev, Ivan J; Nasipak, Brian T; Padilla-Benavides, Teresita; Wu, Qiong; Imbalzano, Anthony N; Nickerson, Jeffrey A; Bunnage, Mark E; Müller, Susanne; Knapp, Stefan; Owen, Dafydd R


    The acetyl post-translational modification of chromatin at selected histone lysine residues is interpreted by an acetyl-lysine specific interaction with bromodomain reader modules. Here we report the discovery of the potent, acetyl-lysine-competitive, and cell active inhibitor PFI-3 that binds to certain family VIII bromodomains while displaying significant, broader bromodomain family selectivity. The high specificity of PFI-3 for family VIII was achieved through a novel bromodomain binding mode of a phenolic headgroup that led to the unusual displacement of water molecules that are generally retained by most other bromodomain inhibitors reported to date. The medicinal chemistry program that led to PFI-3 from an initial fragment screening hit is described in detail, and additional analogues with differing family VIII bromodomain selectivity profiles are also reported. We also describe the full pharmacological characterization of PFI-3 as a chemical probe, along with phenotypic data on adipocyte and myoblast cell differentiation assays.

  8. Drevnerusskij pamflet na Mihaila VIII Paleologa v svete germenevtičeskogo analiza

    Directory of Open Access Journals (Sweden)

    Demincev Mihail


    Full Text Available In the article the perception of the image of Michael VIII Palaeologus by literate citizens of Tsardom of Russia is considered. The study is based on analysis of writings that date back to XVII century. The study focuses on identifying the symbols and latent ideas, that point to a semantic connection of the studied writings with The Old Testament, Apocalypse and some antique texts. In the end of the article the authjr makes a conclusion, that the perception of the image of Michael VIII Palaeologus in Tsardom of Russia was negative.

  9. Wavelengths and energy levels of Xe VII and Xe VIII obtained by collision-based spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Larsson, M.O. [Uppsala Univ. (Sweden). Dept. of Theoretical Physics; Gonzalez, A.M. [Centro de Investigaciones Energeticas, Medioambientales y Tecnologicas (CIEMAT), Madrid (Spain). Inst. de Investigacion Basica; Hallin, R. [Uppsala Univ. (Sweden). Dept. of Theoretical Physics; Heijkenskjoeld, F. [Uppsala Univ. (Sweden). Dept. of Theoretical Physics; Hutton, R. [Lund Univ. (Sweden). Dept. of Physics; Langereis, A. [Uppsala Univ. (Sweden). Dept. of Theoretical Physics; Nystroem, B. [Lund Univ. (Sweden). Dept. of Physics; O`Sullivan, G. [University Coll., Dublin (Ireland). Dept. of Physics; Waennstroem, A. [Uppsala Univ. (Sweden). Dept. of Theoretical Physics


    The Xe VII and Xe VIII spectra have been investigated by collision-based spectroscopy. The radiation emitted following electron capture by 10q keV Xe{sup q+} ions (q = 6-8) impinging on a He (Ar) gas target has, with some exceptions, been recorded in the 350-8000 (1200-2500) A wavelength region. The xenon ions were provided by the Uppsala University ECR ion source. Many of the observed, previously unreported spectral lines have been identified. In total, nine new energy levels of Xe VII and Xe VIII have been established, of which two are tentative. The analysis was supported by Hartree-Fock calculations. (orig.).

  10. Acquired factor VIII inhibitor (acquired hemophilia A) presenting as spontaneous blood-filled scrotum. (United States)

    Verma, Rajanshu; Noack, Jill; Vemuri, Radhakrishna; Loehrke, Mark E


    Acquired hemophilia A, also known as acquired factor VIII deficiency, is an exceedingly rare bleeding diathesis that does not require any personal or family history of bleeding or clotting disorder. Because treatment is available, misdiagnosing or completely missing this diagnosis can be life threatening for patients. Clinicians should be aware that acquired forms of hemophilia do exist and are associated with high morbidity and mortality in elderly adults. We present a case of a 74-year-old man who was diagnosed with acquired factor VIII inhibitor during an admission for community-acquired pneumonia.

  11. Simultaneous dual syringe electrospinning system using benign solvent to fabricate nanofibrous P(3HB-co-4HB)/collagen peptides construct as potential leave-on wound dressing

    Energy Technology Data Exchange (ETDEWEB)

    Vigneswari, S. [Malaysian Institute of Pharmaceuticals and Nutraceuticals, NIBM, MOSTI, 11700 Penang (Malaysia); Institute of Marine Biotechnology, Universiti Malaysia Terengganu, 21030 Kuala Terengganu (Malaysia); Murugaiyah, V. [School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11700 Penang (Malaysia); Kaur, G. [Institute of Research in Molecular Medicine, Universiti Sains Malaysia, 11700 Penang (Malaysia); Abdul Khalil, H.P.S. [School of Industrial Technology, Universiti Sains Malaysia, 11700 Penang (Malaysia); Amirul, A.A., E-mail: [Malaysian Institute of Pharmaceuticals and Nutraceuticals, NIBM, MOSTI, 11700 Penang (Malaysia); School of Biological Sciences, Universiti Sains Malaysia, 11800 Penang (Malaysia); Centre of Chemical Biology, Universiti Sains Malaysia, 11900 Penang (Malaysia)


    The main focus of this study is the incorporation of collagen peptides to fabricate P(3-hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-4HB)] nano-fiber construct to further enhance surface wettability and support cell growth while harbouring desired properties for biodegradable wound dressing. Simultaneous electrospinning of nanofiber P(3HB-co-4HB)/collagen peptides construct was carried out using dual syringe system. The wettability of the constructs increased with the increase in 4HB molar fraction from 20 mol% 4HB [53.2°], P(3HB-co-35 mol%4HB)[48.9°], P(3HB-co-50 mol%4HB)[44.5°] and P(3HB-co-82 mol%4HB) [37.7°]. In vitro study carried out using mouse fibroblast cells (L929) grown on nanofiber P(3HB-co-4HB)/collagen peptides construct showed an increase in cell proliferation. In vivo study using animal model (Sprague Dawley rats) showed that nanofibrous P(3HB-co-4HB)/collagen peptides construct had a significant effect on wound contractions with the highest percentage of wound closure of 79%. Hence, P(3HB-co-4HB)/collagen peptides construct suitable for wound dressing have been developed using nano-fabrication technique. - Highlights: • Nano-fiber construct to enhance surface wettability and cell growth, harbouring desired properties as biodegradable wound dressing. • Simultaneous electrospinning of nanofiber P(3HB-co-4HB)/collagen construct using dual syringe system. • Nanofibrous construct accelerated wound healing with efficient cellular organization.

  12. 46 CFR 54.01-2 - Adoption of division 1 of section VIII of the ASME Boiler and Pressure Vessel Code. (United States)


    ... 46 Shipping 2 2010-10-01 2010-10-01 false Adoption of division 1 of section VIII of the ASME... division 1 of section VIII of the ASME Boiler and Pressure Vessel Code. (a) Pressure vessels shall be designed, constructed, and inspected in accordance with section VIII of the ASME Boiler and Pressure Vessel...

  13. Variation in baseline factor VIII concentration in a retrospective cohort of mild/moderate hemophilia A patients carrying identical F8 mutations

    NARCIS (Netherlands)

    Loomans, J.I.; Velzen, A.S. van; Eckhardt, C.L.; Peters, M.; Makipernaa, A.; Holmstrom, M.; Brons, P.P.T.; Dors, N.; Haya, S.; Voorberg, J.; Bom, J.G. Van Der; Fijnvandraat, K.


    Essentials Factor VIII levels vary in mild and moderate hemophilia A (MHA) patients with the same mutation. We aimed to estimate the variation and determinants of factor VIII levels among MHA patients. Age and genotype explain 59% of the observed inter-individual variation in factor VIII levels.

  14. A targetable HB-EGF-CITED4 axis controls oncogenesis in lung cancer. (United States)

    Hsieh, C-H; Chou, Y-T; Kuo, M-H; Tsai, H-P; Chang, J-L; Wu, C-W


    Aberrant epidermal growth factor (EGF) receptor (EGFR) signaling contributes to neoplastic initiation and progression in lung. Mutated EGFR has become as an important therapeutic target in lung cancer, whereas targeted treatment is not available for wild-type EGFR or its ligands. In this study, we found that heparin-binding (HB)-EGF, a member of the EGF family, was highly expressed in a subset of lung cancer, proliferation of which was dependent on HB-EGF signaling. Silencing of HB-EGF with RNA interference inhibited cell cycle progression in lung cancer cells. We observed that, upon HB-EGF induction, CITED4 was induced through a signal transducer and activator of transcription 3 (STAT3)-dependent pathway, regulating cell proliferation. CITED4 interacted with MYC and potentiated MYC-mediated transactivation of the CCND1 promoter, leading to cell cycle progression. Correlation analysis revealed that HB-EGF and CITED4 were significantly positively associated in primary lung tumors, and expression of HB-EGF predicted a poor survival outcome in patients. In vitro and in vivo experiments revealed that pharmacological inhibition of HB-EGF with CRM197 significantly attenuated tumor cell growth. Thus, CITED4 functions as a molecular switch in HB-EGF-induced growth control, and HB-EGF provides a novel therapeutic target for lung cancer intervention.

  15. HB-EGF expression as a potential biomarker of acquired middle ear cholesteatoma. (United States)

    Xie, Shumin; Wang, Xiaoli; Ren, Hongmiao; Liu, Xiaoyu; Ren, Jihao; Liu, Wei


    The heparin-binding epidermal growth factor-like growth factor (HB-EGF) plays an essential role in the development and invasiveness of cholesteatoma. This study may help to realize the molecular mechanisms underlying the pathogenesis of cholesteatoma and make HB-EGF a promising target for drug intervention of cholesteatoma. To detect HB-EGF expression in human surgical specimens of acquired middle ear cholesteatoma and analyze its functional role as a regulator of epithelial keratinocytes hyperproliferation. A total of 34 patients who underwent surgical treatment for middle ear cholesteatoma were recruited in the study. The mRNA and protein expression of HB-EGF in middle ear cholesteatoma tissues and normal postauricular skin tissues was investigated by real-time quantitative reverse-transcription-polymerase chain reaction (RT-qPCR), immunohistochemical staining, and western blot. The correlation between bone resorption degree and HB-EGF expression was also analyzed. On average, compared with normal postauricular skin, expression of HB-EGF mRNA in the cholesteatoma epithelium was significantly elevated 2.41-fold by RT-qPCR, and HB-EGF protein significantly upregulated 2.32-fold by western blot. Positive HB-EGF immunostaining observed in the basal and suprabasal layers of cholesteatoma epithelium was significantly stronger than in normal postauricular skin. Meanwhile, an obviously positive correlation between HB-EGF protein expression and bone resorption degree was discovered.

  16. HbA1c, fasting plasma glucose and the prediction of diabetes

    DEFF Research Database (Denmark)

    Soulimane, Soraya; Simon, Dominique; Shaw, Jonathan


    With diabetes defined by HbA1c≥6.5% and/or FPG≥7.0mmol/l and/or diabetes treatment, we investigated HbA1c and fasting plasma glucose (FPG) thresholds/change-points above which the incidence of diabetes increases.......With diabetes defined by HbA1c≥6.5% and/or FPG≥7.0mmol/l and/or diabetes treatment, we investigated HbA1c and fasting plasma glucose (FPG) thresholds/change-points above which the incidence of diabetes increases....

  17. Prevalence and predictors of the sub-target Hb level in children on dialysis

    DEFF Research Database (Denmark)

    van Stralen, Karlijn J; Krischock, Leah; Schaefer, Franz


    Anaemia is a common and potentially treatable co-morbidity of end-stage renal disease. We aimed to determine the prevalence of the sub-target haemoglobin (Hb) level among European children on dialysis and to identify factors associated with a low Hb level.......Anaemia is a common and potentially treatable co-morbidity of end-stage renal disease. We aimed to determine the prevalence of the sub-target haemoglobin (Hb) level among European children on dialysis and to identify factors associated with a low Hb level....

  18. Desain Pembelajaran Materi Luas Permukaan Prisma Menggunakan Pendekatan PMRI bagi Siswa Kelas VIII

    Directory of Open Access Journals (Sweden)

    Djuwita Trisnawati


    Full Text Available Penelitian ini bertujuan menghasilkan lintasan belajar untuk membantu siswa dalam pembelajaran luas permukaan prisma menggunakan kemasan produk di kelas VIII SMP. Penelitian ini berdasarkan PMRI yang dikaitkan dengan pembelajaran Kurikulum 2006/KTSP. Metode yang digunakan dalam penelitian ini adalah design research type validation study yang bertujuan untuk membuktikan teori-teori pembelajaran. Penelitian ini dilaksanakan di SMP Negeri 24 Palembang dengan melibatkan siswa kelas VIII yang berjumlah 31 siswa. Aktivitas-aktivitas pembelajaran yang dilakukan siswa meliputi: 1 memahami bentuk dan sifat prisma, 2 menemukan dan memahami konsep luas permukaan prisma, dan 3 menyelesaikan permasalahan dalam kehidupan sehari-hari yang berhubungan dengan luas permukaan prisma. Hasil dari penelitian ini menunjukkan bahwa melalui serangkaian aktivitas yang telah dilakukan membantu siswa dalam pembelajaran luas permukaan prisma.This research aimed to produce learning trajectory in learning surface area of prism using product packaging in class VIII. This study was based PMRI associated with learning curriculum 2006 / KTSP. The method used was design research of type validation study that aimed to prove the theories of learning. The research was conducted on 31 students of class VIII SMPN 24 Palembang. Students learning activities that were conducted including: (1 comprehending the shape and the characteristic of prism, (2 finding and comprehending the concept surface area of prism, and (3 solving the problems in daily life related to the surface area of prism. The results of this study indicate that a series of activities can help students in learning surface area of prism.

  19. A natural anatoxin, Amm VIII, induces neutralizing antibodies against the potent scorpion alpha-toxins. (United States)

    Martin-Eauclaire, M-F; Alami, M; Giamarchi, A; Missimilli, V; Rosso, J-P; Bougis, P E


    In this study, we have used Amm VIII, a natural anatoxin from the scorpion Androctonus mauretanicus mauretanicus, to elicit specific polyclonal antibodies in rabbit. Using liquid-phase radioimmunoassay, we have studied its selectivity and its neutralizing activity both in vitro and in vivo for the most lethal scorpion alpha-toxins described, in particular the alpha-toxin of reference AaH II. We have shown that the anti-Amm VIII serum prevents the association of 125I-AaH II with its receptor and is able to remove 125I-AaH II already bound to its site (the half-life of the complex 125I-AaH II-receptor site was 12 min in the absence of anti-Amm VIII serum but decreased to only 2 min in the presence of anti-Amm VIII serum). In vivo, the serum also has a protective effect in mice: 42 LD50 of AaH II by millilitre are neutralized, measured by subcutaneous injection.

  20. Analysis of mutations in the entire coding sequence of the factor VIII gene

    Energy Technology Data Exchange (ETDEWEB)

    Bidichadani, S.I.; Lanyon, W.G.; Connor, J.M. [Glascow Univ. (United Kingdom)] [and others


    Hemophilia A is a common X-linked recessive disorder of bleeding caused by deleterious mutations in the gene for clotting factor VIII. The large size of the factor VIII gene, the high frequency of de novo mutations and its tissue-specific expression complicate the detection of mutations. We have used a combination of RT-PCR of ectopic factor VIII transcripts and genomic DNA-PCRs to amplify the entire essential sequence of the factor VIII gene. This is followed by chemical mismatch cleavage analysis and direct sequencing in order to facilitate a comprehensive search for mutations. We describe the characterization of nine potentially pathogenic mutations, six of which are novel. In each case, a correlation of the genotype with the observed phenotype is presented. In order to evaluate the pathogenicity of the five missense mutations detected, we have analyzed them for evolutionary sequence conservation and for their involvement of sequence motifs catalogued in the PROSITE database of protein sites and patterns.

  1. In vivo recovery and safety of human factor VIII product AAFACT in patients with haemophilia A

    NARCIS (Netherlands)

    Vossebeld, P. J. M.; Tissing, M. H.; van den Berg, H. M.; Leebeek, F. W. G.; de Goede-Bolder, A.; Novakova, I. R. O.; Gerrits, W. B. J.; Peters, M.; Koopman, M. M. W.; Faber, A.; Hiemstra, H.; Grob, P.; Strengers, P. F. W.


    AAFACT, a monoclonal purified, solvent/detergent treated human plasma-derived coagulation factor VIII concentrate obtained from plasma of voluntary, non-remunerated blood donors, is manufactured and marketed in the Netherlands by Sanquin Plasma Products since 1995. In a postmarketing surveillance

  2. Intercombination lines of AlVIII, AlIX, and AlX ions (United States)

    Denne, B.; Hinnov, E.


    Several aluminum lines observed in the Princeton Large Torus tokamak discharges have been identified as intersystem transitions, establishing the energies of the Al VIII 2s2p35S, Al IX 2s2p24P, and Al X 2s2p3P terms. Some observations of isoelectronic transitions in scandium and titanium ions are also reported.

  3. Living in a physical world VIII. Gravity and life in water

    Indian Academy of Sciences (India)


    Jul 31, 2006 ... Home; Journals; Journal of Biosciences; Volume 31; Issue 3. Living in a physical world VIII. Gravity and life in water. Steven Vogel. Series Volume 31 Issue 3 September 2006 pp 309-322. Fulltext. Click here to view fulltext PDF. Permanent link: ...

  4. Idiopathic factor VIII inhibitor autoantibody in a man presented after accident.

    NARCIS (Netherlands)

    Mansouritorghabeh, H.; Lak, M.; Heerde, W.L. van


    Acquired hemophilia A is a rare but severe autoimmune bleeding disorder caused by autoantibodies against factor VIII activity and is a potentially life-threatening hemorrhagic disorder. The incidence of acquired hemophilia A has been estimated as 1.48 cases per million per year. The overall rate of

  5. Safety and Efficacy of BAY 94-9027, a Prolonged-Half-Life Factor VIII

    DEFF Research Database (Denmark)

    Reding, M T; Ng, H J; Poulsen, Lone Hvitfeldt


    BACKGROUND: BAY 94-9027 is a B-domain-deleted prolonged-half-life recombinant factor VIII (FVIII) conjugates in a site-specific manner with polyethylene glycol. OBJECTIVE: Assess efficacy and safety of BAY 94-9027 for prophylaxis and treatment of bleeds in patients with severe hemophilia A PATIEN...

  6. Factor VIII and von Willebrand factor co-delivery by endothelial cells

    NARCIS (Netherlands)

    Bouwens, E.A.M.


    A defect in coagulation factor VIII (FVIII) results in the inherited bleeding disorder hemophilia A. Current treatment of hemophilia A is hampered by the need of frequent administration of costly FVIII products. Therefore gene therapy is an attractive alternative for protein replacement to treat

  7. Storage and regulated secretion of factor VIII in blood outgrowth endothelial cells

    NARCIS (Netherlands)

    van den Biggelaar, M.; Bouwens, E.A.M.; Kootstra, N.A.; Hebbel, R.P.; Voorberg, J.; Mertens, K.


    Background Gene therapy provides an attractive alternative for protein replacement therapy in hemophilia A patients. Recent studies have shown the potential benefit of directing factor (F)VIII gene delivery to cells that also express its natural carrier protein von Willebrand factor (VWF). In this

  8. Endocytic receptor for pro-coagulant factor VIII: relevance to inhibitor formation. (United States)

    Navarrete, Ana-Maria; Dasgupta, Suryasarathi; Teyssandier, Maud; Repesse, Yohann; Delignat, Sandrine; André, Sébastien; Bayry, Jagadeesh; Kaveri, Srinivas V; Lacroix-Desmazes, Sébastien


    The immunogenicity of therapeutic factor VIII (FVIII) in patients with haemophilia A remains a critical issue in patient management. This review describes the immunological processes involved in the activation of the immune system against FVIII, with a particular focus on the role of endocytic receptors for the recognition of FVIII by antigen-presenting cells.

  9. Limited promiscuity of HLA-DRB1 presented peptides derived of blood coagulation factor VIII

    NARCIS (Netherlands)

    van Haren, Simon D.; Wroblewska, Aleksandra; Herczenik, Eszter; Kaijen, Paul H.; Ruminska, Aleksandra; ten Brinke, Anja; Meijer, Alexander B.; Voorberg, Jan


    The formation of inhibitory antibodies directed against coagulation factor VIII (FVIII) is a severe complication in the treatment of hemophilia A patients. The induction of anti-FVIII antibodies is a CD4(+) T cell-dependent process. Activation of FVIII-specific CD4(+) T cells is dependent on the

  10. Molecular characterization of a novel family VIII esterase from burkholderia multivorans UWC10

    CSIR Research Space (South Africa)

    Rashamuse, KJ


    Full Text Available was identified. Full-length sequencing of the DNA insert showed that it consisted of a single open reading frame (ORF1) encoding a predicted protein of 398 amino acids. ORF1 (termed EstBL) had a high protein sequence identity to family VIII esterases. The Est...

  11. The beta + IVS, I-NT no. 6 (T --> C) thalassaemia in heterozygotes with an associated Hb Valletta or Hb S heterozygosity in homozygotes from Malta. (United States)

    Scerri, C A; Abela, W; Galdies, R; Pizzuto, M; Grech, J L; Felice, A E


    In vitro DNA amplification and dot blot analysis with synthetic allele specific oligonucleotides (ASO) identified the beta + IVS, I-6 (T --> C) thalassaemia in 78% of 32 chromosomes from 16 beta-thalassaemia homozygotes in Malta. The preponderance of a single thalassaemia mutation in one population is unusual. The beta + IVS, I-6C thalassaemia mutation was also found in three carriers who had an associated beta globin heterozygosity, i.e. Hb Valletta (or alpha 2 beta 2 87PRO) or Hb S (or alpha 2 beta 2 6VAL). The proportion of Hb A in these cases (av. = 29.7%) provided objective documentation of the relatively mild effect of this mutation on in vivo globin gene expression. However, the expression of homozygous disease was more severe in developing children compared to adults. The beta + IVS, I-6C mutation complicates population testing because heterozygotes can have Hb A2 levels below those classically associated with beta thalassaemia.

  12. Assessing glycaemic control in diabetes: relationships between fructosamine and HbA1C. (United States)

    Braatvedt, G D; Drury, P L; Cundy, T


    Glycated haemoglobin (HbA1C) has become the internationally established method of assessing long term glycaemic control in people with diabetes. In New Zealand the measurement of glycated albumin (fructosamine), which is substantially cheaper than HbA1C has been widely adopted. In this study we have sought to determine if the value of HbA1C can be reliably estimated from knowledge of plasma fructosamine. Fifty subjects with diabetes and stable glycaemic control as assessed by 3-5 simultaneous measurements of HbA1C and fructosamine made sequentially over a median of 6 months, were studied. The relationship between the two measures was assessed by determining 95% prediction intervals for HbA1C from the regression equation relating mean HbA1C and fructosamine. A further 8 subjects with significantly changing glycaemic control were also studied. Mean stable plasma fructosamine and HbA1C measurements were closely correlated (r = 0.661, p < 0.0001) with HbA1C increasing on average 1% for every 56 mumol L-1 increase in fructosamine. The prediction intervals for HbA1C were however wide. Thus at a plasma fructosamine of 350 mumol L-1 the 95% prediction intervals for HbA1C ranged from 6.6 to 11.2% (3 to 11 standard deviations above the mean of the normal reference range). This variability could not be accounted for by the presence of albuminuria or by the exclusion of those subjects with the greatest variability in fructosamine. In the subjects showing changes in glycaemic control, a change in HbA1C of 1% was associated with a change in fructosamine of between 29 and 63 mumol L-1. Fructosamine levels generally correlate well with HbA1C within a population but the value of HbA1C in an individual cannot be inferred with any reliability from the level of fructosamine, nor can the change in HbA1C be inferred from the change in fructosamine. We suggest that if fructosamine is to be used as an index of glycaemic control in diabetes, it is supplemented by a measurement of HbA1C

  13. VIII Olimpíada Brasileira de Astronomia e Astronáutica (United States)

    Garcia Canalle, João Batista; Villas da Rocha, Jaime Fernando; Wuensche de Souza, Carlos Alexandre; Pereira Ortiz, Roberto; Aguilera, Nuricel Villalonga; Padilha, Maria De Fátima Catta Preta; Pessoa Filho, José Bezerra; Soares Rodrigues, Ivette Maria


    Neste trabalho apresentamos as motivações pelas quais organizamos, em conjunto, pela primeira vez, a Olimpíada Brasileira de Astronomia incluindo a Astronáutica, em colaboração com a Agência Espacial Brasileira. Esta ampliação contribuiu para atrair ainda mais alunos, professores, escolas e patrocinadores para participarem desta Olimpíada. Em 2005 participaram da VIII Olimpíada Brasileira de Astronomia e Astronáutica (VIII OBA) 187.726 alunos distribuídos por 3.229 escolas, pertencentes a todos os estados brasileiros, incluindo o Distrito Federal. O crescimento em número de alunos participantes foi 52,4% maior do que em 2004. Em abril de 2005 organizamos, em Itapecerica da Serra, SP, um curso para os 50 alunos previamente selecionados e participantes da VII OBA e ao final selecionamos, dentre eles, uma equipe de 5 alunos, os quais representaram o Brasil na X Olimpíada Internacional de Astronomia, na China, em outubro de 2005. Ganhamos, pela primeira vez, uma medalha de ouro naquele evento. Em Agosto de 2005, organizamos a VIII Escola de Agosto para 50 alunos e respectivos professores, em Águas de Lindóia, SP, juntamente com a XXXI reunião anual da Sociedade Astronômica Brasileira (SAB). Em novembro de 2005 realizamos a I Jornada Espacial, em São José dos Campos, com 22 alunos e 22 professores selecionados dentre os participantes que melhores resultados obtiveram nas questões de Astronáutica da VIII OBA. Neste trabalho detalhamos os resultados da VIII OBA bem como as ações subseqüentes.


    Directory of Open Access Journals (Sweden)

    Putri Athirah Azis


    Full Text Available The study aims at examining (1 the correlation of learning interest towards learning result of grade students, (2 the correlation of learning motivation towards learning result of grade students, (3 the correlation of students attitude towards learning result, (4 the correlationof interest, learning motivation, and attitude collaboratively towards learning result. The study is an ex post facto. The population of the study was grade VIII at SMPN 13 Makassar. Samples were 105 students taken by employing random sampling technique. Data were collected through questionnaire and documentation. Data were analyzed using regression test. The result of study reveal that (1 there is significant correlation (p<0,01 of interest towards learning result of grade VIII students at SMPN 13 Makassar. Co-efficient correlation (r is 0,718 and its effectiveness contribution (R2 is 51,5%, (2 there is significant correlation (p<0,01 of motivation towards learning result of grade VIII students at SMPN 13 Makassar. Co-efficient correlation (r is 0,775 and its effectiveness contribution (R2 is 60,1%, (3 there is significant correlation (p<0,01 of attitude towards learning result of grade VIII students at SMPN 13 Makassar. Co-efficient correlation (r is 0,737 and its effectiveness contribution (R2 is 54,4%, (4 there is significant correlation (p<0,01 of interest, motivation and attitude collaboratively towards learning result of grade VIII students at SMPN 13 Makassar. Co-efficient correlation (r is 0,861 and its effectiveness contribution (R2 is 74,1%,

  15. Impact of Mean Cell Hemoglobin on Hb A1c-Defined Glycemia Status. (United States)

    Rodriguez-Segade, Santiago; Garcia, Javier Rodriguez; García-López, José M; Gude, Francisco; Casanueva, Felipe F; Rs-Alonso, Santiago; Camiña, Félix


    Several hematological alterations are associated with altered hemoglobin A1c (Hb A1c). However, there have been no reports of their influence on the rates of exceeding standard Hb A1c thresholds by patients for whom Hb A1c determination is requested in clinical practice. The initial data set included the first profiles (complete blood counts, Hb A1c, fasting glucose, and renal and hepatic parameters) of all adult patients for whom such a profile was requested between 2008 and 2013 inclusive. After appropriate exclusions, 21844 patients remained in the study. Linear and logistic regression models were adjusted for demographic, hematological, and biochemical variables excluded from the predictors. Mean corpuscular hemoglobin (MCH) and mean corpuscular volume (MCV) correlated negatively with Hb A1c. Fasting glucose, MCH, and age emerged as predictors of Hb A1c in a stepwise regression that discarded sex, hemoglobin, MCV, mean corpuscular hemoglobin concentration (MCHC), serum creatinine, and liver disease. Mean Hb A1c in MCH interdecile intervals fell from 6.8% (51 mmol/mol) in the lowest (≤27.5 pg) to 6.0% (43 mmol/mol) in the highest (>32.5 pg), with similar results for MCV. After adjustment for fasting glucose and other correlates of Hb A1c, a 1 pg increase in MCH reduced the odds of Hb A1c-defined dysglycemia, diabetes and poor glycemia control by 10%-14%. For at least 25% of patients, low or high MCH or MCV levels are associated with increased risk of an erroneous Hb A1c-based identification of glycemia status. Although causality has not been demonstrated, these parameters should be taken into account in interpreting Hb A1c levels in clinical practice. © 2016 American Association for Clinical Chemistry.

  16. The heparin-binding domain of HB-EGF mediates localization to sites of cell-cell contact and prevents HB-EGF proteolytic release

    Energy Technology Data Exchange (ETDEWEB)

    Prince, Robin N.; Schreiter, Eric R.; Zou, Peng; Wiley, H. S.; Ting, Alice Y.; Lee, Richard T.; Lauffenburger, Douglas A.


    Heparin-binding EGF-like growth factor (HB-EGF) is a ligand for EGF receptor (EGFR) and possesses the ability to signal in juxtacrine, autocrine and/or paracrine mode, with these alternatives being governed by the degree of proteolytic release of the ligand. Although the spatial range of diffusion of released HB-EGF is restricted by binding heparan-sulfate proteoglycans (HSPGs) in the extracellular matrix and/or cellular glycocalyx, ascertaining mechanisms governing non-released HB-EGF localization is also important for understanding its effects. We have employed a new method for independently tracking the localization of the extracellular EGFlike domain of HB-EGF and the cytoplasmic C-terminus. A striking observation was the absence of the HB-EGF transmembrane proform from the leading edge of COS-7 cells in a wound-closure assay; instead, this protein localized in regions of cell-cell contact. A battery of detailed experiments found that this localization derives from a trans interaction between extracellular HSPGs and the HBEGF heparin-binding domain, and that disruption of this interaction leads to increased release of soluble ligand and a switch in cell phenotype from juxtacrine-induced growth inhibition to autocrine-induced proliferation. Our results indicate that extracellular HSPGs serve to sequester the transmembrane pro-form of HB-EGF at the point of cell-cell contact, and that this plays a role in governing the balance between juxtacrine versus autocrine and paracrine signaling.

  17. Hb Dartmouth (HBA2: c.200T>C): An α2-Globin Gene Associated with Hb H Disease in One Homozygous Patient. (United States)

    Farashi, Samaneh; Faramarzi Garous, Negin; Ashki, Mehri; Vakili, Shadi; Zeinali, Fatemah; Imanian, Hashem; Azarkeivan, Azita; Najmabadi, Hossein


    Hb H (β4) disease is caused by deletion or inactivation of three out of four α-globin genes. A high incidence of Hb H disease has been reported all over the world. There is a wide spectrum of phenotypic presentations, from clinically asymptomatic to having significant hepatosplenomegaly and requiring occasional or even regular blood transfusions, even more severe anemia, Hb Bart's (γ4) hydrops fetalis syndrome that can cause death in the affected fetuses late in gestation. We here present a case who was diagnosed with Hb H disease that represents a new genotype for this hereditary disorder. Hb Dartmouth is a variant caused by a missense mutation at codon 66 of the α2-globin gene (HBA2: c.200T>C), resulting in the substitution of leucine by proline. We here emphasize the importance of this point mutation involving Hb H disease and also the necessity for prenatal diagnosis (PND) for those who carry this point mutation in the heterozygous state.

  18. Transcriptional regulation of Hb-α and Hb-β through nuclear factor E2-related factor-2 (Nrf2) activation in human vaginal cells: A novel mechanism of cellular adaptability to oxidative stress. (United States)

    Saha, Debarchana; Koli, Swanand; Reddy, Kudumula Venkata Rami


    Hemoglobin (Hb), a major protein involved in transport of oxygen (O2 ), is expressed by erythroid lineages. Until recently, it was not known whether non-erythroid cells express Hb. The objective was to evaluate the expression and functional significance of Hb-α and Hb-β in human primary vaginal epithelial cells (hPVECs) and decipher downstream signaling. RT-PCR, qRT-PCR, flow cytometry, Western blot, immunofluorescence were used to evaluate the expression of Hb-α, Hb-β, and nuclear factor E2-related factor-2(Nrf2) after hydrogen peroxide (H2 O2 ) induction. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assay were used to determine the binding efficiency of Nrf2 on the Hb-α promoter. Stimulation of hPVECs and human vaginal epithelial cell line, VK2/E6E7 with H2 O2 augmented the expression of Hb-α, Hb-β, Nrf2, heme oxygenase-1 (HO-1), and reactive oxygen species (ROS). Treatment of these cells with Nrf2 inhibitor, trigonelline (Trig) inhibited Hb-α and Hb-β expressions. Hb-α and Hb-β overexpression downregulated H2 O2 -induced ROS. The presence of Nrf2 binding domain was demonstrated within Hb-α promoter. The results revealed for the first time that Hb-α and Hb-β were induced by oxidative stress through the activation of Nrf2. Overexpression of Hb-α and Hb-β ameliorated H2 O2 -induced oxidative stress, indicating one of the possible mechanism(s) to protect hPVECS from oxidative stress. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. The Hb E (HBB: c.79G>A), Mean Corpuscular Volume, Mean Corpuscular Hemoglobin Cutoff Points in Double Heterozygous Hb E/- -SEA α-Thalassemia-1 Carriers are Dependent on Hemoglobin Levels. (United States)

    Leckngam, Prapapun; Limweeraprajak, Ektong; Kiewkarnkha, Tiemjan; Tatu, Thanusak


    Identifying double heterozygosities in Hb E (HBB: c.79 G>A)/- -SEA (Southeast Asian) (α-thalassemia-1) (α-thal-1) in patients first diagnosed as carrying Hb E is important in thalassemia control. Low Hb E, mean corpuscular volume (MCV) and mean corpuscular hemoglobin (Hb) (MCH) levels have been observed in this double heterozygosity. However, the cutoff points of these parameters have never been systematically established. Here, we analyzed Hb E and red blood cell (RBC) parameters in 372 Hb E patients grouped by Hb levels, by the status of - -SEA and -α3.7 (α-thal-2; rightward) deletions, to establish the cutoff points. Then, the established cutoff points were evaluated in 184 Hb E patients. It was found that the cutoff points of Hb E, MCV, MCH were significantly dependent on the Hb levels. In the group having Hb levels <10.0 g/dL, the cutoff points of Hb E, MCV and MCH were 21.2%, 64.9 fL and 21.0 pg, respectively, and were 25.6%, 72.8 fL and 23.9 pg, respectively, in the group having Hb levels 10.0-11.9 g/dL. Finally, in the group having Hb levels ≥12.0 g/dL, the cutoff points of Hb E, MCV and MCH were 27.1%, 76.7 fL and 25.3 pg, respectively. Thus, to screen for the double heterozygous Hb E/- -SEA anomaly in patients initially diagnosed as carrying Hb E, the Hb levels must be taken into account in choosing the suitable cutoff points of these three parameters.

  20. Comparison of International Expert Committee value of HbA1c and ...

    African Journals Online (AJOL)

    Background: The international expert committee recommendations on the use of HbA1c in the diagnosis of diabetes mellitus has just come on board. Thus, it is imperative to compare its performance with existing accepted standard for diagnosing diabetes mellitus. Objective: To use the new cut-off value of HbA1c of >6.5% ...

  1. Identification of diphtheria toxin R domain mutants with enhanced inhibitory activity against HB-EGF. (United States)

    Suzuki, Keisuke; Mizushima, Hiroto; Abe, Hiroyuki; Iwamoto, Ryo; Nakamura, Haruki; Mekada, Eisuke


    Heparin-binding epidermal growth factor-like growth factor (HB-EGF), a ligand of EGF receptor, is involved in the growth and malignant progression of cancers. Cross-reacting material 197, CRM197, a non-toxic mutant of diphtheria toxin (DT), specifically binds to the EGF-like domain of HB-EGF and inhibits its mitogenic activity, thus CRM197 is currently under evaluation in clinical trials for cancer therapy. To develop more potent DT mutants than CRM197, we screened various mutant proteins of R domain of DT, the binding site for HB-EGF. A variety of R-domain mutant proteins fused with maltose-binding protein were produced and their inhibitory activity was evaluated in vitro. We found four R domain mutants that showed much higher inhibitory activity against HB-EGF than wild-type (WT) R domain. These R domain mutants suppressed HB-EGF-dependent cell proliferation more effectively than WT R domain. Surface plasmon resonance revealed their higher affinity to HB-EGF than WT R domain. CRM197(R460H) carrying the newly identified mutation showed increased cell proliferation inhibitory activity and affinity to HB-EGF. These results suggest that CRM197(R460H) or other recombinant proteins carrying newly identified mutation(s) in the R domain are potential therapeutics targeting HB-EGF. © The Authors 2014. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

  2. High maternal HbA1c is associated with overweight in neonates

    DEFF Research Database (Denmark)

    Mikkelsen, Maria R.; Nielsen, Sigrid Bruun; Stage, E


    The aims of this study were to determine the prevalence of women with gestational diabetes mellitus (GDM) not obtaining HbA1c within the normal range (= 5.6%) before delivery and to examine whether elevated HbA1c values are associated with an increased risk of large for gestational age (LGA...


    Ruangrai, Waraporn; Jindadamrongwech, Sumalee


    Genetic factors influencing Hb F content in adult red blood cells include β-thalassemia genotypes, co-inheritance of α-thalassemia traits and single nucleotide polymorphisms (SNPs). Genotyping of α- and β-thalassemia and five SNPs in β-globin gene cluster previously identified in genome-wide association studies as being markers of elevated Hb F in β-thalassemia were performed in 81 subjects diagnosed with β-thalassemia/Hb E. Hb F levels are higher (0.9-7.1 g/dl) in subjects (n = 57) with the severe compared to mild β-thalassemia (0.8-2.5 g/ dl) (n = 4) genotypes, and are similarly low (0.7-3.5 g/dl) in those (n = 15) with α-thalassemia co-inheritance. Hb F levels in non-thalassemia controls (n = 150) range from 0 to 0.15 g/dl. The presence of homozygous minor alleles of the 5 SNPs are significant indicators of β-thalassemia/Hb E individuals with high Hb F (> 4 g/dl), independent of their thalassemia genotypes. Given that re-activation of γ-globin genes leads to amelioration of β-thalassemia severity, understanding how genetic factors up-regulate Hb F production may lead to possible therapeutic interventions, genetically or pharmacologically, of this debilitating disease in the not too distant future.

  4. High maternal HbA1c is associated with overweight in neonates

    DEFF Research Database (Denmark)

    Mikkelsen, Maria R.; Nielsen, Sigrid Bruun; Stage, E


    The aims of this study were to determine the prevalence of women with gestational diabetes mellitus (GDM) not obtaining HbA1c within the normal range (≤ 5.6%) before delivery and to examine whether elevated HbA1c values are associated with an increased risk of large for gestational age (LGA...

  5. Faster heme loss from hemoglobin E than HbS, in acidic pH: Effect ...

    Indian Academy of Sciences (India)

    mutant hemoglobin(s) resulting in abnormal structure of one of the globin chains, called hemoglobinopathy. Sickle cell disease (SCD) is the classical example of such a disease where a point mutation [β6 (A3) Glu→Val] in the β-globin chain forms sickle hemoglobin, HbS (Dickerson and Geis 1983). Deoxy HbS readily forms ...

  6. HB 1347 and Its Relationship to Foodservice Outsourcing in Illinois Public Schools (United States)

    Brashear, Gary L.


    This study examined foodservice outsourcing in the State of Illinois. School administrators currently outsourcing foodservice were surveyed about their perceptions of HB1347 and its components. This study looked at HB1347 in Illinois, and its effects on outsourcing in school districts. Data for this study was collected from a survey sent to 100%…

  7. Falsely decreased HbA1c in a type 2 diabetic patient treated with dapsone. (United States)

    Lai, Ying-Chuen; Wang, Chou-Shiang; Wang, Yi-Ching; Hsu, Yu-Ling; Chuang, Lee-Ming


    Glycated hemoglobin A1c (HbA1c) is an important indicator of glycemic control. The current recommendation for glycemic control based on HbA1c values has been widely accepted. However, HbA1c values depend on the lifespan of erythrocytes and the assay methods used. Here, we report the case of a patient with type 2 diabetes with unusual falling of HbA1c due to interference from dapsone treatment for leukocytoclastic vasculitis. He was a 52-year-old man, who was diagnosed with type 2 diabetes mellitus 5 years previously and who had been treated in our hospital in the past 3 years. Glycemia was controlled by sulfonylurea and metformin. During the 3-years follow-up period, HbA1c dropped significantly during the addition of dapsone treatment, although plasma glucose levels remained stable. HbA1c levels were raised after discontinuation of dapsone. With rechallenge of dapsone usage, HbA1c decreased again. We conclude that dapsone may be the cause of artificially low HbA1c. Other measurements to monitor glycemic control should be considered when dapsone is used for the treatment of concurrent disorders, such as autoimmune disease and pneumocystis jiroveci pneumonia. Copyright © 2012. Published by Elsevier B.V.

  8. Spinal Hb9::Cre-derived excitatory interneurons contribute to rhythm generation in the mouse. (United States)

    Caldeira, Vanessa; Dougherty, Kimberly J; Borgius, Lotta; Kiehn, Ole


    Rhythm generating neurons are thought to be ipsilaterally-projecting excitatory neurons in the thoracolumbar mammalian spinal cord. Recently, a subset of Shox2 interneurons (Shox2 non-V2a INs) was found to fulfill these criteria and make up a fraction of the rhythm-generating population. Here we use Hb9::Cre mice to genetically manipulate Hb9::Cre-derived excitatory interneurons (INs) in order to determine the role of these INs in rhythm generation. We demonstrate that this line captures a consistent population of spinal INs which is mixed with respect to neurotransmitter phenotype and progenitor domain, but does not overlap with the Shox2 non-V2a population. We also show that Hb9::Cre-derived INs include the comparatively small medial population of INs which continues to express Hb9 postnatally. When excitatory neurotransmission is selectively blocked by deleting Vglut2 from Hb9::Cre-derived INs, there is no difference in left-right and/or flexor-extensor phasing between these cords and controls, suggesting that excitatory Hb9::Cre-derived INs do not affect pattern generation. In contrast, the frequencies of locomotor activity are significantly lower in cords from Hb9::Cre-Vglut2(Δ/Δ) mice than in cords from controls. Collectively, our findings indicate that excitatory Hb9::Cre-derived INs constitute a distinct population of neurons that participates in the rhythm generating kernel for spinal locomotion.

  9. The heritability of HbA1c and fasting blood glucose in different measurement settings.

    NARCIS (Netherlands)

    Bik-Simonis, A.M.C.; Eekhoff, E.M.W.; Diamant, M.; Boomsma, D.I.; Heine, R.J.; Dekker, J.M.; Willemsen, G.; van Leeuwen, M.; de Geus, E.J.C.


    In an extended twin study we estimated the heritability of fasting HbA1c and blood glucose levels. Blood glucose was assessed in different settings (at home and in the clinic). We tested whether the genetic factors influencing fasting blood glucose levels overlapped with those influencing HbA1c and

  10. Changes in proHB-EGF expression after functional activation of the immune system cells

    Directory of Open Access Journals (Sweden)

    T. O. Chudina


    Full Text Available The level of proHB-EGF expression on J774, Raji, KG-1 cells derived from different types of human and mouse immune system cells under the standard in vitro culture conditions and during functional activation of these cells was investigated. Changes in the proHB-EGF expression on the cell surface were found to depend on the density of cell population, the content of fetal bovine serum in the culture medium, the effect of mitogenic factors – bacterial lipopolysaccharide, an inactive full-size form of diphtheria toxin (CRM197 and recombinant soluble HB-EGF – rsHB-EGF. The results obtained are important for the understanding of the functional role of proHB-EGF receptor on the surface of macrophage-like cells and B lymphocytes and indicate the involvement of this receptor in immune response regulation in an organism.

  11. [Propositions for the standardized expression of HbA 1c results]. (United States)

    Gillery, P; Périer, C; Bordas-Fonfrède, M; Hue, G; Chapelle, J-P; Vexiau, P; Vialettes, B


    The 2007 international consensus about the standardization of HbA(1c) determination and expression of results is progressively implemented in most countries. In France, a common working group of the Société française de biologie clinique (SFBC) and the Société francophone de diabétologie (SFD) has expressed the following recommendations. HbA(1c) results are expressed in percentage of total hemoglobin and in mmol HbA(1c)/mol Hb, but are not converted into estimated average glucose. A table indicating the correspondence between HbA(1c) and estimated average glucose may be given with the results, subject to precautions of interpretation at the individual level.

  12. The heparin-binding domain of HB-EGF mediates localization to sites of cell-cell contact and prevents HB-EGF proteolytic release (United States)

    Prince, Robin N.; Schreiter, Eric R.; Zou, Peng; Wiley, H. Steven; Ting, Alice Y.; Lee, Richard T.; Lauffenburger, Douglas A.


    Heparin-binding EGF-like growth factor (HB-EGF) is a ligand for EGF receptor (EGFR) and possesses the ability to signal in juxtacrine, autocrine and/or paracrine mode, with these alternatives being governed by the degree of proteolytic release of the ligand. Although the spatial range of diffusion of released HB-EGF is restricted by binding heparan-sulfate proteoglycans (HSPGs) in the extracellular matrix and/or cellular glycocalyx, ascertaining mechanisms governing non-released HB-EGF localization is also important for understanding its effects. We have employed a new method for independently tracking the localization of the extracellular EGF-like domain of HB-EGF and the cytoplasmic C-terminus. A striking observation was the absence of the HB-EGF transmembrane pro-form from the leading edge of COS-7 cells in a wound-closure assay; instead, this protein localized in regions of cell-cell contact. A battery of detailed experiments found that this localization derives from a trans interaction between extracellular HSPGs and the HB-EGF heparin-binding domain, and that disruption of this interaction leads to increased release of soluble ligand and a switch in cell phenotype from juxtacrine-induced growth inhibition to autocrine-induced proliferation. Our results indicate that extracellular HSPGs serve to sequester the transmembrane pro-form of HB-EGF at the point of cell-cell contact, and that this plays a role in governing the balance between juxtacrine versus autocrine and paracrine signaling. PMID:20530570

  13. Detection of the Unstable Hb Köln (HBB: c.295G>A) by a Capillary Electrophoresis Method. (United States)

    Li, You-Qiong; Ye, Li-Hua; Mo, Yun


    Hb Köln (HBB: c.295G>A) is an unstable β-globin gene variant with a GTG>ATG substitution at codon 98. This variant is quite frequent in Europe and the USA but rare in China. It can easily be misdiagnosed as Hb Constant Spring (Hb CS; HBA2: c.427T>C) by high performance liquid chromatography (HPLC), but detection and quantification of both Hb Köln and degraded Hb Köln by capillary electrophoresis (CE) are possible. Thus, we concluded that CE was the preferred method for Hb Köln detection.

  14. 75 FR 26196 - Notice of Proposed New Recreation Fee Site; Federal Lands Recreation Enhancement Act, (Title VIII... (United States)


    ..., (Title VIII, Pub. L. 108-447) AGENCY: National Forests in Mississippi, Forest Service, USDA. ACTION... 39269. SUPPLEMENTARY INFORMATION: The Federal Recreation Lands Enhancement Act (Title VII, Pub. L. 108...


    National Research Council Canada - National Science Library



    The author examines the positive and negative effects of social media on the moral education of children in school SMPN 2 class VIII Banda Aceh, it is very interesting because of the many children who abuse social media...

  16. A novel approach in potential anticoagulants from peptides epitope 558-565 of A2 subunit of factor VIII. (United States)

    Anastasopoulos, C; Sarigiannis, Y; Stavropoulos, G


    Factor VIII, a human blood plasma protein, plays an important role during the intrinsic pathway of blood coagulation cascade after its activation by thrombin. The activated form of FVIII acts as cofactor to the serine protease Factor IXa, in the conversion of the zymogen Factor X to the active enzyme Factor Xa. The Ser558-Gln565 region of the A2 subunit of Factor VIII has been shown to be crucial for FVIIIa-FIXa interaction. Based on this, a series of linear peptides, analogs of the 558-565 loop of the A2 subunit of the heavy chain of Factor VIII were synthesized using the acid labile 2-chlorotrityl chloride resin and biologically evaluated in vitro by measuring the chronic delay of activated partial thromboplastin time and the inhibition of Factor VIII activity, as potential anticoagulants.

  17. Evaluation of the Tosoh G8 Analyzer and Comparison with the Trinity Biotech Premier Hb9210 Analyzer for the Measurement of HbA₁c. (United States)

    Ucar, Fatma; Erden, Gonul; Ozdemir, Seyda; Yildiz, Zeynep; Arzuhal, Abdullah Ercan; Temel, Ismail


    The aim of our study was to assess the analytical performance of the Tosoh HLC-723G8 automated analyzer and to compare it with the Trinity Biotech Premier Hb9210 analyzer for the measurement of hemoglobin A₁c (HbA₁c). A total of 101 patients with pre-diabetes or diabetes mellitus were included in the study. HbA₁c, was measured by both an ion-exchange high-performance liquid chromatography (IE-HPLC) method and a boronate affinity chromatography method. Statistical analysis was performed using Deming regression. Bland-Altman plots were used to calculate mean difference (bias). The CV% values of IE-HPLC and boronate affinity methods for within run and between days were lower than 2.0%. High correlation was found (y = 1.0045x + 0.2111; r = 0.9941) between the two methods. The method shows no interference from carbamylated hemoglobin. Both systems showed acceptable performance and are suitable for clinical application in the analysis of HbA₁c. However, laboratories should be aware of the limitations of their methods and the availability of more accurate and precise HbA₁c, determination methods.

  18. Interaction of - α 3.7, ß Thalassemia Mutation IVS 1-5 and HbD Punjab in a Family: A Case Report


    Pandey, S.; Ranjan, Ravi; Mishra, R. M.; Pandey, Sw.; Saxena, R.


    Hemoglobin D exist in four form; HbD trait, HbD-thalassemia, HbD sickle cell and HbD homozygous. HbD trait and HbD homozygous generally asymptomatic condition but when HbD co-inherit with thalassemia and sickle cell anemia, produces clinically significant conditions like chronic hemolytic anemia. Here we present a case of HbD Punjab with α 3.7 kb deletion and IVS-1-5 β-thalassemia across a family. Diagnosis of HbD patient was performed by high performance liquid chromatography and complete bl...


    Directory of Open Access Journals (Sweden)

    Nurmiyati Nurmiyati


    Full Text Available Penelitian ini bertujuan untuk mengetahui: (1 apakah ada perbedaan keefektifan antara teknik paired storytelling, jigsaw, dan konvensional dalam meningkatkan kompetensi berbicara siswa, (2 teknik pembelajaran berbicara yang paling efektif antara ketiga teknik penelitian itu dalam meningkatkan kompetensi berbicara siswa kelas VIII SMP Negeri 3 Sleman. Penelitian ini menggunakan jenis penelitian eksperimen semu dengan nonequivalent control-group design. Hasil penelitian menunjukkan bahwa: (1 Ada perbedaan keefektifan antara teknik paired storytelling, jigsaw, and konvensional itu dalam meningkatkan kompetensi berbicara siswa dengan nilai F sebesar 3,532 dan signifikan dengan P < 0,05, yaitu sebesar 0,033, dan (2 teknik paired storytelling adalah teknik keterampilan berbicara yang paling efektif diantara ketiga teknik itu dalam meningkatkan kompetensi berbicara siswa kelas VIII SMP Negeri 3 Sleman dengan mean tertinggi sebesar 74,3492. Kata kunci: teknik paired storytelling, teknik jigsaw, teknik konvensional, kompetensi berbicara

  20. Genomic characterisation of the toxin Amm VIII from the scorpion Androctonus mauretanicus mauretanicus. (United States)

    Alami, Meriem; Céard, Brigitte; Legros, Christian; Bougis, Pierre E; Martin-Eauclaire, Marie-France


    The genomic DNA sequence encoding the scorpion toxin Amm VIII was amplified from genomic DNA of the scorpion Androctonus mauretanicus mauretanicus from Morocco, subcloned and sequenced. An intron, with a high A+T content (73.5%), split a Gly codon at the end of the precursor signal peptide and the consensus GT/AG splice junction was identified in the Amm VIII gene. This intron of only 166 bp is the smallest intron described so far for a long-chain scorpion toxin gene. In addition, this study led to the identification of three new toxin-related genes. From the deduced amino acid sequences of the encoded precursor proteins, we found that the mature putative toxins were highly similar to the scorpion toxins Leiurus quinquestriatus quinquestriatus IV and Odonthobuthus doriae 1.

  1. Detection of Intracellular Factor VIII Protein in Peripheral Blood Mononuclear Cells by Flow Cytometry

    Directory of Open Access Journals (Sweden)

    Gouri Shankar Pandey


    Full Text Available Flow cytometry is widely used in cancer research for diagnosis, detection of minimal residual disease, as well as immune monitoring and profiling following immunotherapy. Detection of specific host proteins for diagnosis predominantly uses quantitative PCR and western blotting assays. In this study, we optimized a flow cytometry-based detection assay for Factor VIII protein in peripheral blood mononuclear cells (PBMCs. An indirect intracellular staining (ICS method was standardized using monoclonal antibodies to different domains of human Factor VIII protein. The FVIII protein expression level was estimated by calculating the mean and median fluorescence intensities (MFI values for each monoclonal antibody. ICS staining of transiently transfected cell lines supported the method's specificity. Intracellular FVIII protein expression was also detected by the monoclonal antibodies used in the study in PBMCs of five blood donors. In summary, our data suggest that intracellular FVIII detection in PBMCs of hemophilia A patients can be a rapid and reliable method to detect intracellular FVIII levels.

  2. Acquired hemophilia A caused by factor VIII inhibitors: report of a case. (United States)

    Hosoya, Yoshinori; Matsumura, Miho; Madoiwa, Seiji; Zuiki, Toru; Matsumoto, Shiro; Nunomiya, Shin; Lefor, Alan; Sata, Naohiro; Yasuda, Yoshikazu


    We report a case of acquired hemophilia A (AHA) after esophageal resection. The patient was an 80-year-old woman whose preoperative activated partial-thromboplastin time (APTT) was well within the normal range, at 34.9 s. She underwent thoracic esophagectomy and gastric pull-up for superficial esophageal cancer (operative time, 315 min; intraoperative blood loss, 245 ml). Intrathoracic and subcutaneous bleeding occurred spontaneously on postoperative day (POD) 39. The APTT was prolonged, at 140 s, and factor VIII inhibitor was 36 Bethesda U/ml. Treatment with recombinant activated factor VII, prednisolone, and cyclophosphamide resulted in remission within 2 months. This case supports an association between surgery and the triggering of factor VIII inhibitors. The diagnosis of AHA requires clinical acumen and must be considered in any patient with bleeding and a prolonged APTT.

  3. Treatment of radiation osteomyelitis of the mandible in a patient with acquired factor VIII inhibitor

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    Arimoto, Takamasa; Kishimoto, Hiromitsu; Matsumoto, Suwako; Kawanaka, Masao; Urabe, Masahiro; Yoshioka, Wataru [Hyogo Coll. of Medicine, Nishinomiya (Japan)


    A case of radiation osteomyelitis of mandible in a 56-year-old man with acquired factor VIII inhibitor is presented. He had undergone radiation therapy for malignant lymphoma of the tonsilar region seven years earlier, and also had received steroids to treat acquired factor VIII inhibitor for a year. On initial examination, he was given a diagnosis of phlegmon of the cheek caused by pericoronitis of the left lower wisdom tooth. To prevent the recurrence of inflammation, the wisdom tooth was extracted carefully, but radiation osteomyelitis occurred in association with a pathological fracture of the condylar head. After mini-pulse therapy with methylpredonisolone, segmental mandibulectomy and reconstruction with a titanium metal plate were performed. The postoperative course was satisfactory with no complications such as bleeding or infection. (author)

  4. Can the Afinion HbA1c Point-of-Care instrument be an alternative method for the Tosoh G8 in the case of Hb-Tacoma? (United States)

    Lenters-Westra, Erna; Strunk, Annuska; Campbell, Paul; Slingerland, Robbert J


    Hb-variant interference when reporting HbA1c has been an ongoing challenge since HbA1c was introduced to monitor patients with diabetes mellitus. Most Hb-variants show an abnormal chromatogram when cation-exchange HPLC is used for the determination of HbA1c. Unfortunately, the Tosoh G8 generates what appears to be normal chromatogram in the presence of Hb-Tacoma, yielding a falsely high HbA1c value. The primary aim of the study was to investigate if the Afinion HbA1c point-of-care (POC) instrument could be used as an alternative method for the Tosoh G8 when testing for HbA1c in the presence of Hb-Tacoma. Whole blood samples were collected in K2EDTA tubes from individuals homozygous for HbA (n = 40) and heterozygous for Hb-Tacoma (n = 20). Samples were then immediately analyzed with the Afinion POC instrument. After analysis, aliquots of each sample were frozen at -80 °C. The frozen samples were shipped on dry ice to the European Reference Laboratory for Glycohemoglobin (ERL) and analyzed with three International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) and National Glycohemoglobin Standardization Program (NGSP) Secondary Reference Measurement Procedures (SRMPs). The Premier Hb9210 was used as the reference method. When compared to the reference method, samples with Hb-Tacoma yielded mean relative differences of 31.8% on the Tosoh G8, 21.5% on the Roche Tina-quant Gen. 2 and 16.8% on the Afinion. The Afinion cannot be used as an alternative method for the Tosoh G8 when testing for HbA1c in the presence of Hb-Tacoma.

  5. Pengembangan Modul Matematika Untuk Pembelajaran Berbasis Masalah (Problem Based Learning) Pada Materi Pokok Persamaan Garis Lurus Kelas VIII SMP


    Khayati, Fitrotul; Sujadi, Imam; Sari Saputro, Dewi Retno


    Absrtact:The objectives of this research were to investigate: (1) how to develop of Mathematics module development for problem-based learning on the topic of discussion of Linear Equation of Straight Line for Grade VIII of Junior Secondary School; and (2) the effectiveness of result of Mathematics module development for problem-based learning on the topic of discussion of Linear Equation of Straight Line for Grade VIII of Junior Secondary School. This research consisted of two phases. The fi...

  6. HB-EGF is necessary and sufficient for Müller glia dedifferentiation and retina regeneration (United States)

    Wan, Jin; Ramachandran, Rajesh; Goldman, Daniel


    Summary Müller glia (MG) dedifferentiation into a cycling population of multipotent progenitors is crucial to zebrafish retina regeneration. The mechanisms underlying MG dedifferentiation are unknown. Here we report that heparin-binding epidermal-like growth factor (HB-EGF) is rapidly induced in MG residing at the injury site and that proHB-EGF ectodomain shedding is necessary for retina regeneration. Remarkably, HB-EGF stimulates the formation of multipotent MG-derived progenitors in the uninjured retina. We show that HB-EGF mediates its effects via an EGFR/MAPK signal transduction cascade that regulates the expression of regeneration-associated genes, like ascl1a and pax6b. We also uncover an HB-EGF/Ascl1a/Notch/hb-egfa signaling loop that helps define the zone of injury-responsive MG. Finally, we show that HB-EGF acts upstream of the Wnt/β-catenin signaling cascade that controls progenitor proliferation. These data provide a link between extracellular signaling and regeneration-associated gene expression in the injured retina and suggest strategies for stimulating retina regeneration in mammals. PMID:22340497

  7. Electrochemical sensor based on magnetic molecularly imprinted nanoparticles modified magnetic electrode for determination of Hb. (United States)

    Sun, Binghua; Ni, Xinjiong; Cao, Yuhua; Cao, Guangqun


    A fast and selective electrochemical sensor for determination of hemoglobin (Hb) was developed based on magnetic molecularly imprinted nanoparticles modified on the magnetic glassy carbon electrode. The nanoparticles Fe3O4@SiO2 with a magnetic core and a molecularly imprinted shell had regular structures and good monodispersity. Hb could be determined directly by electrochemical oxidization with the modified electrode. A magnetic field increased electrochemical response to Hb by two times. Imprinting Hb on the surface of Fe3O4@SiO2 shortened the response time within 7min. Under optimum conditions, the imprinting factor toward the non-imprinted sensor was 2.8, and the separation factor of Hb to horseradish peroxidase was 2.6. The oxidation peak current had a linear relationship with Hb concentration ranged from 0.005mg/ml to 0.1mg/ml with a detection limit (S/N =3) of 0.0010mg/ml. The sensors were successfully applied to analysis of Hb in whole blood samples with recoveries between 95.7% and 105%. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Updates of the HbVar database of human hemoglobin variants and thalassemia mutations. (United States)

    Giardine, Belinda; Borg, Joseph; Viennas, Emmanouil; Pavlidis, Cristiana; Moradkhani, Kamran; Joly, Philippe; Bartsakoulia, Marina; Riemer, Cathy; Miller, Webb; Tzimas, Giannis; Wajcman, Henri; Hardison, Ross C; Patrinos, George P


    HbVar ( is one of the oldest and most appreciated locus-specific databases launched in 2001 by a multi-center academic effort to provide timely information on the genomic alterations leading to hemoglobin variants and all types of thalassemia and hemoglobinopathies. Database records include extensive phenotypic descriptions, biochemical and hematological effects, associated pathology and ethnic occurrence, accompanied by mutation frequencies and references. Here, we report updates to >600 HbVar entries, inclusion of population-specific data for 28 populations and 27 ethnic groups for α-, and β-thalassemias and additional querying options in the HbVar query page. HbVar content was also inter-connected with two other established genetic databases, namely FINDbase ( and Leiden Open-Access Variation database (, which allows comparative data querying and analysis. HbVar data content has contributed to the realization of two collaborative projects to identify genomic variants that lie on different globin paralogs. Most importantly, HbVar data content has contributed to demonstrate the microattribution concept in practice. These updates significantly enriched the database content and querying potential, enhanced the database profile and data quality and broadened the inter-relation of HbVar with other databases, which should increase the already high impact of this resource to the globin and genetic database community.

  9. Influence of the type of factor VIII concentrate on the incidence of factor VIII inhibitors in previously untreated patients with severe hemophilia A. (United States)

    Goudemand, Jenny; Rothschild, Chantal; Demiguel, Virginie; Vinciguerrat, Christine; Lambert, Thierry; Chambost, Hervé; Borel-Derlon, Annie; Claeyssens, Ségolène; Laurian, Yves; Calvez, Thierry


    Inhibitor development is the major treatment complication in children with severe hemophilia A. It is not clear whether the risk of inhibitors is higher with recombinant factor VIII or with plasma-derived factor VIII. We used multivariate analysis to compare 2 cohorts of previously untreated patients (PUPs) with severe hemophilia A: 62 patients treated with the same brand of high-purity plasma-derived FVIII (pFVIII) containing von Willebrand factor (VWF) and 86 patients treated with full-length recombinant FVIII (rFVIII). In addition to the usual end points (all inhibitors, high inhibitors), we also examined a third end point (high inhibitors and/or immune tolerance induction). The risk of inhibitor development was higher in patients treated with rFVIII than in patients treated with pFVIII, regardless of other risk factors (F8 genotype; nonwhite origin; history of inhibitors in patients with a family history of hemophilia; age at first FVIII infusion). The adjusted relative risk (RRa) for inhibitor development with rFVIII versus pFVIII was 2.4 (all inhibitors), 2.6 (high inhibitors), and 3.2 (high inhibitors and/or immune tolerance induction), respectively, depending on the end point (above). The pathophysiology of this large effect must be understood in order to improve the characteristics of recombinant products and to reduce the incidence of inhibitors to FVIII.



    A. Setyowati; B. Subali; Mosik -


    Tujuan dari penelitian ini adalah untuk mengetahui pengaruh implementasi pendekatan konflik kognitif dalam pembelajaran fisikapokok bahasan tekanan pada siswa kelas VIII terhadap kemampuan berpikir kritis, pemahaman konsep dan hasil belajar kognitifsiswa. Penelitian ini merupakan penelitian eksperimen. Setelah dilakukan pengambilan sampel secara random sampling,diperoleh kelas VIIIB sebagai kelas eksperimen dan kelas VIIIC sebagai kelas kontrol. Dari analisis uji rata-rata dua pihak atau uji ...

  11. Construction of a mouse model of factor VIII deficiency by gene targeting

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    Bi, L.; Lawler, A.; Gearhart, J. [Univ. of Pennsylvania School of Medicine, Philadelphia, PA (United States)] [and others


    To develop a small animal model of hemophilia A for gene therapy experiments, we set out to construct a mouse model for factor VIII deficiency by gene targeting. First, we screened a mouse liver cDNA library using a human FVIII cDNA probe. We cloned a 2.6 Kb partial mouse factor VIII cDNA which extends from 800 base pairs of the 3{prime} end of exon 14 to the 5{prime} end of exon 26. A mouse genomic library made from strain 129 was then screened to obtain genomic fragments covering the exons desired for homologous recombination. Two genomic clones were obtained, and one covering exon 15 through 22 was used for gene targeting. To make gene targeting constructs, a 5.8 Kb genomic DNA fragment covering exons 15 to 19 of the mouse FVIII gene was subcloned, and the neo expression cassette was inserted into exons 16 and 17 separately by different strategies. These two constructs were named MFVIIIC-16 and MFVIIIC-17. The constructs were linearized and transfected into strain 129 mouse ES cells by electroporation. Factor VIII gene-knockout ES cell lines were selected by G-418 and screened by genomic Southern blots. Eight exon 16 targeted cell lines and five exon 17 targeted cell lines were obtained. Three cell lines from each construct were injected into blastocysts and surgically transferred into foster mothers. Multiple chimeric mice with 70-90% hair color derived from the ES-cell genotype were seen with both constructs. Germ line transmission of the ES-cell genotype has been obtained for the MFVIIIC-16 construct, and multiple hemophilia A carrier females have been identified. Factor VIII-deficient males will be conceived soon.

  12. Historical intensity VIII earthquakes along the Rhone valley (Valais, Switzerland): primary and secondary effects

    Energy Technology Data Exchange (ETDEWEB)

    Fritsche, S.; Faeh, D.; Schwarz-Zanetti, G.


    In recent years the upper Rhone Valley has been one of the most intensively investigated regions by the Swiss Seismological Service. The high seismicity in the region encourages research in the seismological field and one main focus has been historical seismology. This report presents the state of the art of our historical investigations by giving an overview of the effects of four damaging earthquakes with intensity larger than VII, for which a fairly large number of documents could be found and analyzed. The overview includes the events of 1584 (Aigle, epicentral intensity VIII), 1755 (Brig, epicentral intensity VIII), 1855 (Visp, epicentral intensity VIII), and 1946 (Sierre, epicentral intensity VIII for the main shock and intensity VII for the largest aftershock). The paper focuses mainly on primary and secondary effects in the epicentral region, providing the key data and a general characterization of the event. Generally, primary effects such as the reaction of the population and impact on buildings took more focus in the past. Thus building damage is more frequently described in historic documents. However, we also found a number of sources describing secondary effects such as landslides, snow avalanches, and liquefaction. Since the sources may be useful, we include citations of these documents. The 1584 Aigle event, for example, produced exceptional movements in the Lake of Geneva, which can be explained by an expanded sub aquatic slide with resultant tsunami and seiche. The strongest of the aftershocks of the 1584 event triggered a destructive landslide covering the villages Corbeyrier and Yvorne, Vaud. All macroseismic data on the discussed events are accessible through the web page of the Swiss Seismological Service ( (authors)

  13. The impact of von Willebrand factor on factor VIII memory immune responses


    Chen, Juan; Schroeder, Jocelyn A.; Luo, Xiaofeng; Shi, Qizhen


    Immune tolerance induction (ITI) with aggressive infusion of factor VIII (FVIII) is the current strategy used to eradicate FVIII inhibitors and restore normal FVIII pharmacokinetics in inhibitor patients. Whether the use of FVIII products containing von Willebrand factor (VWF) will affect the efficacy of ITI is still controversial. In this study, we explored the impact of VWF on FVIII memory immune responses in hemophilia A (HA) mice. A T-cell proliferation assay and cytokine profile analysis...

  14. Endonuclease VIII-like 3 (Neil3) DNA glycosylase promotes neurogenesis induced by hypoxia-ischemia


    Sejersted, Yngve; Hildrestrand, Gunn A.; Kunke, David; Rolseth, Veslemøy; Krokeide, Silje Z.; Neurauter, Christine G.; Suganthan, Rajikala; Atneosen-Åsegg, Monica; Fleming, Aaron M.; Saugstad, Ola D.; Burrows, Cynthia J.; Luna, Luisa; Bjørås, Magnar


    Neural stem/progenitor cell proliferation and differentiation are required to replace damaged neurons and regain brain function after hypoxic-ischemic events. DNA base lesions accumulating during hypoxic-ischemic stress are removed by DNA glycosylases in the base-excision repair pathway to prevent cytotoxicity and mutagenesis. Expression of the DNA glycosylase endonuclease VIII-like 3 (Neil3) is confined to regenerative subregions in the embryonic and perinatal brains. Here we show profound n...

  15. Hb and dyslipidaemia as predicting markers of serum alanine aminotransferase elevation in Chinese adolescents. (United States)

    Chao, Kuo-Ching; Chang, Chun-Chao; Owaga, Eddy; Bai, Chyi-Huey; Huang, Tzu-chieh; Pan, Wen-Harn; Chang, Jung-Su


    Fe is an essential element for erythropoiesis and Hb synthesis. High Hb levels affect the blood's viscosity and are associated with cardiovascular dysfunction. The aim of the present study was to examine relationships of Hb and cardiometabolic abnormalities with the risk of alanine aminotransferase (ALT) elevation in adolescents. A population-based, cross-sectional study. National Nutrition and Health Survey in Taiwan (2010-2011, adolescents). Healthy adolescents aged 13-18 years. In total, 1941 adolescents (963 boys and 978 girls) were entered in the study. The mean age was 15·3 (sd 0·1) years (boys, 15·3 (sd 0·1) years; girls, 15·2 (sd 0·1) years). ALT tertile cut-off points for boys were 11 and 16 U/l, and for girls were 9 and 12 U/l. Girls without dyslipidaemia and presenting in the highest quartile (Q1) of Hb (>13·6 g/dl) were 1·89 and 3·76 times more likely to have raised serum ALT (9 and >12 U/l, respectively) than the reference (lowest quartile of Hb (Q1), 12 U/l) than the reference (Q1 of Hb, 15·4 g/dl), who were 7·40 times more likely to have elevated serum ALT of >16 U/l than the reference (Q1 of Hb, Hb level is a predictor of elevated serum ALT in adolescent girls with dyslipidaemia. Our study also highlights the importance of further research to establish cut-off points for Hb and its utility in diagnosing and preventing the onset of dyslipidaemia in adolescents.

  16. Structural characterization of the novel aminoglycoside phosphotransferase AphVIII from Streptomyces rimosus with enzymatic activity modulated by phosphorylation

    Energy Technology Data Exchange (ETDEWEB)

    Boyko, Konstantin M., E-mail: [Bach Institute of Biochemistry, Federal Research Centre of Biotechnology of the Russian Academy of Sciences, Leninsky Prospekt. 33, Bld. 2, 119071, Moscow (Russian Federation); National Research Center “Kurchatov Institute”, Kurchatov Complex of NBICS-technologies, Akad. Kurchatova sqr., 1, Moscow, 123182 (Russian Federation); Gorbacheva, Marina A.; Korzhenevskiy, Dmitry A. [National Research Center “Kurchatov Institute”, Kurchatov Complex of NBICS-technologies, Akad. Kurchatova sqr., 1, Moscow, 123182 (Russian Federation); Alekseeva, Maria G.; Mavletova, Dilara A.; Zakharevich, Natalia V.; Elizarov, Sergey M.; Rudakova, Natalia N.; Danilenko, Valery N. [Vavilov Institute of General Genetics, Russian Academy of Sciences, Gubkina str. 3, Moscow, 119333 (Russian Federation); Popov, Vladimir O. [Bach Institute of Biochemistry, Federal Research Centre of Biotechnology of the Russian Academy of Sciences, Leninsky Prospekt. 33, Bld. 2, 119071, Moscow (Russian Federation); National Research Center “Kurchatov Institute”, Kurchatov Complex of NBICS-technologies, Akad. Kurchatova sqr., 1, Moscow, 123182 (Russian Federation)


    Aminoglycoside phosphotransferases represent a broad class of enzymes that promote bacterial resistance to aminoglycoside antibiotics via the phosphorylation of hydroxyl groups in the latter. Here we report the spatial structure of the 3′-aminoglycoside phosphotransferase of novel VIII class (AphVIII) solved by X-ray diffraction method with a resolution of 2.15 Å. Deep analysis of APHVIII structure and its comparison with known structures of aminoglycoside phosphotransferases of various types reveals that AphVIII has a typical two-domain fold and, however, possesses some unique characteristics that distinguish the enzyme from its known homologues. The most important difference is the presence of the activation loop with unique Ser146 residue. We demonstrate that in the apo-state of the enzyme the activation loop does not interact with other parts of the enzyme and seems to adopt catalytically competent state only after substrate binding. - Highlights: • 3D structure of the novel aminoglycoside phosphotransferase AphVIII was obtained. • AphVIII activation loop is clearly identified in the electron density. • AphVIII has some unique structural features in its substrate C-ring binding pocket.

  17. Neonatal helper-dependent adenoviral vector gene therapy mediates correction of hemophilia A and tolerance to human factor VIII. (United States)

    Hu, Chuhong; Cela, Racel G; Suzuki, Masataka; Lee, Brendan; Lipshutz, Gerald S


    Neonatal gene therapy is a promising strategy for treating a number of congenital diseases diagnosed shortly after birth as expression of therapeutic proteins during postnatal life may limit the pathologic consequences and result in a potential "cure." Hemophilia A is often complicated by the development of antibodies to recombinant protein resulting in treatment failure. Neonatal administration of vectors may avoid inhibitory antibody formation to factor VIII (FVIII) by taking advantage of immune immaturity. A helper-dependent adenoviral vector expressing human factor VIII was administered i.v. to neonatal hemophilia A knockout mice. Three days later, mice produced high levels of FVIII. Levels declined rapidly with animal growth to 5 wk of age with stable factor VIII expression thereafter to >1 y of age. Decline in factor VIII expression was not related to cell-mediated or humoral responses with lack of development of antibodies to capsid or human factor VIII proteins. Subsequent readministration and augmentation of expression was possible as operational tolerance was established to factor VIII without development of inhibitors; however, protective immunity to adenovirus remained.

  18. Low oxygen saturation and severe anemia in compound heterozygous Hb Louisville [β42(CD1)Phe→Leu] and Hb La Desirade [β129(H7)Ala→Val]. (United States)

    Kamseng, Parin; Trakulsrichai, Satariya; Trachoo, Objoon; Yimniam, Walaiporn; Panthan, Bhakbhoom; Jittorntam, Paisan; Niparuck, Pimjai; Sanguanwit, Pitsucha; Wananukul, Winai; Jindadamrongwech, Sumalee


    To investigate the cause(s) of a Thai male proband presenting low oxygen saturation by pulse oximetry (SpO2) and severe anemia. As Hb variant was suspected, Hb typing was determined by high-performance liquid chromatography and capillary electrophoresis, and subsequently Hb variant was identified by DNA sequencing. Complete blood counts were performed using automated blood cell counter and oxygen saturation was measured by pulse oximetry. Proband was compound heterozygous for Hb Louisville [β42(CD1)Phe→Leu] and Hb La Desirade [β129(H7)Ala→Val]. Of the proband's two sons, one was compound heterozygous for Hb Louisville and Hb E and the other for Hb La Desirade and Hb E. The former son had similar clinical features and laboratory findings with those of the proband while the latter showed had no abnormal clinical manifestations. This the first report of compound heterozygosity of Hb Louisville and Hb La Desirade in an individual of Southeast Asian ethnicity. Hb variant identification is crucial for genetic counseling and appropriate treatment in regions where hemoglobinopathies are common.

  19. A close insight to factor VIII inhibitor in the congenital hemophilia A. (United States)

    Tabriznia-Tabrizi, Shamsoreza; Gholampour, Marzie; Mansouritorghabeh, Hassan


    Hemophilia A (HA) has an X-linked pattern of inheritance and is the most common of the hemorrhagic disorders. HA is caused by a decreased or deficiency of the functional clotting factor VIII (FVIII) and effects 1 in 5000-10,000 male births. The common treatment for hemophilia is replacement therapy by plasma-derived or recombinant FVIII. Approximately 20-30% of people with a severe type of HA develop an inhibitor and this phenomenon is the main challenge in the management of these patients. Genetic factors and environmental determinants contribute to inhibitor development. Here, the roles of various genetic and environmental factors such as the type of FVIII concentrate used, the number of exposure days, and peak treatment time will be discussed in detail. It seems this information is helpful for hematologists. A literature review was done in January 2016 on PubMed and Scopus using the following keywords:' h(a)emophilia A & factor VIII inhibitor', 'h(a)emophilia A & factor VIII alloantibody', 'h(a)emophilia A & inhibitor'. There was no time limitation; however, there was an English language limitation placed on the articles selected. Expert commentary: Influential genetic and environmental factors in developing inhibitors have been discussed. Most of the risk factors are related to previously untreated patients with hemophili.

  20. [Structure and function of the factor VIII/von Willebrand factor complex]. (United States)

    Müller, G


    In the blood plasma factor VIII is bound to the von Willebrand factor. The primary structure of the two proteins were clarified by gene clonation. Factor VIII descends from a precursor protein with 2,351 amino acids by splitting of 19 amino acid residues and is activated by partial proteolysis. In the blood coagulation factor VIII acts as co-factor for the activation of factor X by factor IX in the presence of phospholipids and Ca++ within the intrinsic coagulation system. The formation of the von Willebrand factor takes place by splitting of 22 and 741 amino acid residues, respectively, from pre-pro-von Willebrand factor via pro-von Willebrand factor. The subunits of the von Willebrand factor consist od 2,050 amino acid residues. In the blood plasma the von Willebrand factor is existing as a mixture of multimeres. Receptors of the von Willebrand factor on the thrombocytic membrane are the glycoproteins GPIb and GPIIb/GPIIIa, by means of which the adhesion of thrombocytes at the subendoethelium of the vascular wall and the aggregation of thrombocytes are mediated.

  1. Clinical Features and Molecular Analysis of Hb H Disease in Taiwan


    Yu-Hua Chao; Kang-Hsi Wu; Han-Ping Wu; Su-Ching Liu; Ching-Tien Peng; Maw-Sheng Lee


    Thalassemia is highly prevalent in Taiwan, but limited data are available about the association between genotypes and clinical manifestations in Taiwanese patients with Hb H disease. Here, we studied α-globin gene abnormalities and clinical features in Taiwanese patients with Hb H disease. Of the 90 patients, sixty-four (71.1%) were deletional and twenty-six (28.9%) were nondeletional Hb H disease. The (- -SEA) type of α 0-thalassemia mutation was detected in the majority of patients (>95%). ...

  2. The immunogenicity and safety of the new, Indonesian DTwP-HB-Hib vaccine compared to the DTwP/HB vaccine given with the Hib vaccine

    Directory of Open Access Journals (Sweden)

    Novilia Sjafri Bachtiar


    Full Text Available Background Haemophilus influenzae type b (Hib causes infection with predominant manifestations of pneumonia, meningitis, and other invasive diseases, occurring primarily in children aged under 2 years, particularly in infants.  The World Health Organization (WHO and Indonesian Technical Advisory Group for Immunization recommend to include the Hib vaccine into the national immunization program. The newly developed DTwP-HB-Hib combination vaccine is anticipated to be the preferred choice for Hib vaccine introduction; it is efficient, simple, and has higher coverage. Objective To evaluate the immunogenicity and safety of a new, combined Bio Farma DTwP-HB-Hib vaccine, compared to the registered Hib monovalent vaccine given simultaneously with the local DTwP-HB vaccine, when used as the primary vaccination of Indonesian infants. Methods A prospective, randomized, open-label, phase II study was conducted on the DTwP-HB-Hib vaccine compared to the Hib (registered vaccine given simultaneously with the DTwP-HB vaccine, in Bandung from July 2011 to January 2012. Infants were serially vaccinated at 6-11, 10-15, and 14-19 weeks. Serological assessments were done prior to the first vaccine dose and 28 days after the third dose. Safety was assessed from the time of first injection until 1 month after the last injection. Results Of 220 healthy infants enrolled, 211 completed the study, with 105 receiving the combined vaccine and 106 the two separate vaccines. All vaccines were well tolerated. No differences in rates of local and systemic reactions were seen between the two methods of administration. No serious adverse events were considered to be related to the vaccines. In the DTwP-HB-Hib primary-vaccination group, at least 98% of the infants reached protective levels of antibodies (seropositivity against the antigens employed in the vaccines while 96% in the control group. Conclusion The DTwP-HB-Hib combined vaccine is immunogenic and safe, as well as

  3. α-Thalassemia Associated with Hb Instability: A Tale of Two Features. The Case of Hb Rogliano or α1 Cod 108(G15)Thr→Asn and Hb Policoro or α2 Cod 124(H7)Ser→Pro. (United States)

    Musollino, Gennaro; Cardiero, Giovanna; Flagiello, Angela; La Porta, Gaetana; Lagona, Laura; Prezioso, Romeo; Qualtieri, Gabriele; Gaudiano, Carlo; Medulla, Emilia; Merlino, Antonello; Pucci, Piero; Lacerra, Giuseppina


    We identified two new variants in the third exon of the α-globin gene in families from southern Italy: the Hb Rogliano, α1 cod108 ACC>AAC or α1[α108(G15)Thr→Asn] and the Hb Policoro, α2 cod124 TCC>CCC or α2[α124(H7)Ser→Pro]. The carriers showed mild α-thalassemia phenotype and abnormal hemoglobin stability features. These mutations occurred in the G and H helices of the α-globin both involved in the specific recognition of AHSP and β1 chain. Molecular characterization of mRNA, globin chain analyses and molecular modelling studies were carried out to highlight the mechanisms causing the α-thalassemia phenotype. The results demonstrated that the α-thalassemia defect associated with the two Hb variants originated by different defects. Hb Rogliano showed an intrinsic instability of the tetramer due to anomalous intra- and inter-chain interactions suggesting that the variant chain is normally synthesized and complexed with AHSP but rapidly degraded because it is unable to form the α1β1 dimers. On the contrary in the case of Hb Policoro two different molecular mechanisms were shown: the reduction of the variant mRNA level by an unclear mechanism and the protein instability due to impairment of AHSP interaction. These data highlighted that multiple approaches, including mRNA quantification, are needed to properly identify the mechanisms leading to the α-thalassemia defect. Elucidation of the specific mechanism leads to the definition of a given phenotype providing important guidance for the diagnosis of unstable variants. PMID:25730315

  4. Hereditary Persistence of Fetal Hemoglobin Caused by Single Nucleotide Promoter Mutations in Sickle Cell Trait and Hb SC Disease. (United States)

    Akinbami, Anthony O; Campbell, Andrew D; Han, Zeqiu J; Luo, Hong-Yuan; Chui, David H K; Steinberg, Martin H


    Hereditary persistence of fetal hemoglobin (HPFH) can be caused by point mutations in the γ-globin gene promoters. We report three rare cases: a child compound heterozygous for Hb S (HBB: c.20A > T) and HPFH with a novel point mutation in the (A)γ-globin gene promoter who had 42.0% Hb S, 17.0% Hb A and 38.0% Hb F; a man with Hb SC (HBB: c.19G > A) disease and a point mutation in the (G)γ-globin gene promoter who had 54.0% Hb S, 18.0% Hb C and 25.0% Hb F; a child heterozygous for Hb S and HPFH due to mutations in both the (A)γ- and (G)γ-globin gene promoters in cis [(G)γ(A)γ(β(+)) HPFH], with 67.0% Hb A, 6.5% Hb S and 25.0% Hb F.

  5. HbQ-India associated with microcytosis: An uncommon hemoglobin variant associated with a common hematologic condition. (United States)

    Kumar Yadav, Amit; Rusia, Usha


    HbQ-India is a rare alpha chain variant that usually presents in the heterozygous state. Normally, HbQ-India is clinically silent. It becomes symptomatic when present in association with other conditions. We report a case of HbQ-India with concomitant presence of iron deficiency anemia. A 16-year-old female presented with weakness and pallor intermittently for six years. Complete blood count showed severe microcytic hypochromic anemia. Hemoglobin electrophoresis showed a prominent band in the S,D,G region. Tests for sickling were negative. High performance liquid chromatography (HPLC) showed a peak in the unknown window (4.70-4.90 min) suggestive of HbQ-India. Serum iron profile was suggestive of iron deficiency anemia. Based on the above findings, a diagnosis of coexistent HbQ-India-iron deficiency anemia was made. A family study revealed the father as having moderate anemia with similar findings while the mother was normal. Abnormal hemoglobin in the patient was confirmed by molecular diagnosis. HbQ variants are the alpha globin chain variants due to structural mutations (α64 Asp→His) inherited in autosomal dominant fashion. Three molecular variant types have been documented, namely HbQ-India, HbQ-Thailand and HbQ-Iran. Normally, HbQ is clinically silent. Therefore, careful screening of the samples using routine techniques like Hb electrophoresis and HPLC are needed for identification of such abnormal hemoglobin variants like HbQ-India.


    Directory of Open Access Journals (Sweden)

    Rohanawati Silalahi


    Full Text Available Penelitian ini bertujuan untuk meningkatkan pembelajaran menulis puisi bebas melalui media lagu medley siswa kelas VIII B SMP Sintang. Subjek penelitian adalah siswa kelas VIII B SMP Sintang. Penelitian ini merupakan Penelitian Tindakan Kelas (PTK. Prosedur pelaksanaan dan implementasi penelitian dilaksanakan dalam dua siklus. Teknik pengumpulan data berupa obsevasi, wawancara, catatan lapangan, angket, evaluasi dan dokumentasi. Instrumen pengumpulan data meliputi lembar wawancara, lembar catatan lapangan, lembar angket, lembar tes hasil belajar dan lembar portofolio serta dokumentasi foto kegiatan. Teknik analisis data yang digunakan adalah analisis data kuantitatif dan kualitatif. Hasil penelitian ini menunjukkan bahwa penggunaan media lagu medley dapat meningkatkan pembelajaran menulis puisi bebas. Peningkatan hasil atau produk dapat dilihat dari perbandingan skor rata-rata keterampilan menulis puisi bebas siswa pada setiap siklus. Nilai rata-rata siswa pada tahap pratindakan adalah 55,23, pada saat siklus I meningkat menjadi 71,18, dan pada siklus II meningkat menjadi 73,4. ___________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________ DEVELOPING THE TEACHING OF FREE VERSE WRITING THROUGH MEDLEY SONG MEDIA TO GRADE VIII STUDENTS OF SMP SINTANG   Abstract This study aims to improve the teaching of free verse writing through medley song media to Grade VIII B students of SMP Sintang. The research subjects were Grade VIII B students of SMP Sintang,. This was a classroom action research (CAR. The research procedure and implementation were conducted in two cycles. The data were collected through observations, field notes, questionnaires, evaluations, and documentations. The data collecting instruments included interview sheets, field note sheets

  7. HB-GAM (pleiotrophin) reverses inhibition of neural regeneration by the CNS extracellular matrix (United States)

    Paveliev, Mikhail; Fenrich, Keith K.; Kislin, Mikhail; Kuja-Panula, Juha; Kulesskiy, Evgeny; Varjosalo, Markku; Kajander, Tommi; Mugantseva, Ekaterina; Ahonen-Bishopp, Anni; Khiroug, Leonard; Kulesskaya, Natalia; Rougon, Geneviève; Rauvala, Heikki


    Chondroitin sulfate (CS) glycosaminoglycans inhibit regeneration in the adult central nervous system (CNS). We report here that HB-GAM (heparin-binding growth-associated molecule; also known as pleiotrophin), a CS-binding protein expressed at high levels in the developing CNS, reverses the role of the CS chains in neurite growth of CNS neurons in vitro from inhibition to activation. The CS-bound HB-GAM promotes neurite growth through binding to the cell surface proteoglycan glypican-2; furthermore, HB-GAM abrogates the CS ligand binding to the inhibitory receptor PTPσ (protein tyrosine phosphatase sigma). Our in vivo studies using two-photon imaging of CNS injuries support the in vitro studies and show that HB-GAM increases dendrite regeneration in the adult cerebral cortex and axonal regeneration in the adult spinal cord. Our findings may enable the development of novel therapies for CNS injuries. PMID:27671118

  8. A history of HbA1c through Clinical Chemistry and Laboratory Medicine. (United States)

    Gillery, Philippe


    HbA(1c) was discovered in the late 1960s and its use as marker of glycemic control has gradually increased over the course of the last four decades. Recognized as the gold standard of diabetic survey, this parameter was successfully implemented in clinical practice in the 1970s and 1980s and internationally standardized in the 1990s and 2000s. The use of standardized and well-controlled methods, with well-defined performance criteria, has recently opened new directions for HbA(1c) use in patient care, e.g., for diabetes diagnosis. Many reports devoted to HbA1c have been published in Clinical Chemistry and Laboratory Medicine (CCLM) journal. This review reminds the major steps of HbA(1c) history, with a special emphasis on the contribution of CCLM in this field.

  9. Modeling Single-Phase PV HB-ZVR Inverter Connected to Grid

    DEFF Research Database (Denmark)

    Guo, Yougui; Zeng, Ping; Zhu, Jieqiong


    PLECS is used to model the PV H-bridge zero voltage rectifier (HB-ZVR) inverter connected to grid and good results are obtained. First, several common topologies of PV inverters are introduced. Then the unipolar PWM control strategy is described for PV HB-ZVR inverter. Third, PLECS is briefly...... introduced. Fourth, the modeling of PV HB-ZVR inverter is presented with PLECS. Finally, a series of simulations are carried out. The simulation results tell us PLECS is very powerful tool to real power circuits and it is very easy to simulate LCL filter. They have also verified that the unipolar PWM control...... strategy is feasible to control the PV HB-ZVR inverter....

  10. Diagnóstico laboratorial de hemoglobinas semelhantes à HbS Laboratorial diagnosis for hemoglobin like HbS

    Directory of Open Access Journals (Sweden)

    Paula Juliana Antoniazzo Zamaro


    Full Text Available A hemoglobina S (HbS está presente na população brasileira com prevalência variável, dependente dos grupos raciais formadores de cada região. A migração eletroforética em pH alcalino apresenta similaridade com outras hemoglobinas, e estudos complementares para sua correta caracterização são necessários. No presente estudo objetivamos traçar um fluxograma com as metodologias disponíveis para a caracterização da hemoglobina S e das hemoglobinas que apresentam migração semelhante em pH alcalino. No período de janeiro a junho de 2000, analisamos amostras de sangue com suspeita de hemoglobina S encaminhadas ao Laboratório de Hemoglobinas da Unesp. Caracterizamos diferentes mutantes e formas interativas com hemoglobina S, por procedimentos eletroforéticos, em variados pH, análises citológicas e testes bioquímicos específicos. Os procedimentos de análise aplicados resultaram em orientação fornecida aos laboratórios de rotina sobre como proceder no diagnóstico laboratorial destas alterações de hemoglobina. Desta forma contribuímos para um melhor conhecimento sobre a variabilidade genética das hemoglobinas em nossa população, auxiliando no acompanhamento clínico e no aconselhamento genético das hemoglobinopatias com fisiopatologia relacionada à alteração.The hemoglobin S is presented at Brazilian population with variable prevalence dependent of constitutive racial groups in each region. The electrophoretic migration on alkaline pH showed similarities with another hemoglobins. Complementary studies to the correct caracterization becomes necessary. At the present study we aimed make a fluxogram with the avaliable methodologies for the caracterization of hemoglobin S and hemoglobins that present similar migration on alkaline pH. During the period of January to June, 2000, we had analised blood samples with suspicious hemoglobin S sent to the Laboratory of Hemoglobins, Unesp. Were caracterized different mutants and

  11. Comparing risk profiles of individuals diagnosed with diabetes by OGTT and HbA1c

    DEFF Research Database (Denmark)

    Borg, R; Vistisen, D; Witte, Daniel Rinse


    Glycated haemoglobin (HbA(1c)) has been proposed as an alternative to the oral glucose tolerance test for diagnosing diabetes. We compared the cardiovascular risk profile of individuals identified by these two alternative methods.......Glycated haemoglobin (HbA(1c)) has been proposed as an alternative to the oral glucose tolerance test for diagnosing diabetes. We compared the cardiovascular risk profile of individuals identified by these two alternative methods....

  12. Potential use of cord blood for Hb E hemoglobinopathy screening programme using capillary electrophoresis. (United States)

    Wan Mohd Saman, W A; Hassan, R; Mohd Yusoff, S; Che Yaakob, C A; Abdullah, N A F; Ghazali, S; Mohd Radzi, M A R; Bahar, R


    Thalassemia and hemoglobinopathies are inherited red blood cell disorders found worldwide. Hemoglobin (Hb) E disorder is one of the hemoglobinopathies known to have the high prevalence in South East Asia. Most of transfusion-dependent thalassemias were genotypically compound heterozygous Hb E/ β-thalassemia. In Malaysia, the national screening program for thalassemia was implemented for early pregnancy or secondary school girls; however many participants do not turn-up and missed the screening test. Screening for thalassemia using samples from cord blood is an alternative choice as it is a readily available source of blood and hence early detection of the disease. The purpose of this study was to determine the potential use of cord blood for the screening of HbE hemoglobinopathy by using capillary electrophoresis (CE). Cord blood samples were collected from 300 newborns of healthy mothers. Hematological parameters were determined and hemoglobin quantitation for all cord blood samples were performed using capillary electrophoresis system (CES) and high performance liquid chromatography (HPLC). Majority of cord blood samples (63%) revealed Hb AF followed by Hb AFA2 (20%). Hb AFE was detected in 10.7% with the mean value of Hb E ranging from 2.3%-11.1%. Hemoglobin E was detected in cord blood using capillary electrophoresis system. It can be recommended in areas where Hb E/β is prevalent. Implementation of a screening strategy using CE on cord blood sampling will identify the disease early. With regular follow-up on these patients, the status of their disease can be determined earlier and appropriate management implemented.

  13. Faster heme loss from hemoglobin E than HbS, in acidic pH: Effect ...

    Indian Academy of Sciences (India)

    We report studies on loss of heme at or below pH 3.0 from two clinically important hemoglobin variants, HbE and HbS, in the presence and absence of phopholipid membranes. The kinetics of heme loss has been studied at pH 3.0 to simulate the same at a faster rate than at physiological pH, for spectroscopic investigation.

  14. A case of iron deficiency anemia with co-existing Hb Fontainebleau.

    Directory of Open Access Journals (Sweden)

    Abhishek HL Purohit


    Full Text Available Hb Fontainebleaue is a rare alpha chain variant in the Indian population which generates an unknown peak on hemoglobin HPLC study and does cause diagnostic difficulty to those who are not acquainted with this entity. We present a case of Hb Fontainebleau, an eighteen year old patient who presented with symptoms related to anemia to our department and unknown peak observed in HPLC plots lead us to family study and molecular characterization for this case.

  15. Registration of a high yielding malt barley variety HB1454 for the ...

    African Journals Online (AJOL)

    HB1454 (Reg. No. EH 1847/F4.2P.5.2) is a two - rowed, hulled, malting barley developed at Holetta Research Center (HRC). HB 1454 was tested in a multi location variety trial as EH 1847/F4.2P.5.2 from 2005- 2007 along with twelve genotypes advanced from the local crossing program. It was released in 2011 for its high ...

  16. Hb H Hydrops Fetalis Syndrome Caused by Association of the - -(SEA) Deletion and Hb Constant Spring (HBA2: c.427T > C) Mutation in a Chinese Family. (United States)

    He, Sheng; Zheng, Chenguang; Meng, Dahua; Chen, Rongyu; Zhang, Qiang; Tian, Xiaoxian; Chen, Shaoke


    Hb Constant Spring (Hb CS; HBA2: c.427T > C) is an unstable hemoglobin (Hb) variant that results from a nucleotide substitution at the termination codon of the α2-globin gene. Compound heterozygosity for α(0)-thalassemia (α(0)-thal) and Hb CS (- -(SEA)/α(CS)α) results in Hb H/Hb CS disease, which is generally characterized with mild hemolytic anemia, jaundice, and splenomegaly. Here, we describe one case with Hb H/Hb CS disease that presented with fetal anemia and fetal hydrops, known as Hb H (β4) hydrops fetalis. This is the first report of fetal hydrops caused by association of the - -(SEA) deletion and the α(CS)α mutation. Our study highlights the significance of watchful observation using a serial ultrasound method and care of pregnant women who have fetuses found to carry Hb H/Hb CS disease during pregnancy, to guard against the occurrence of fetal hydrops.


    Directory of Open Access Journals (Sweden)

    J.-W. Kim


    Full Text Available We report photometric features of the HB, MSTO, and SGB for a set of metal-poor Galactic globular clusters on the near-IR CMDs. The magnitude and color of the MSTO and SGB are measured on the fiducial normal points of the CMDs by applying a polynomial fit. The near-IR luminosity functions of horizontal branch stars in the classical second parameter pair M3 and M13 indicate that HB stars in M13 are dominated by hot stars that are rotatively faint in the infrared, whereas HB stars in M3 are brighter than those in M13. The luminosity functions of HB stars in the observed bulge clusters, except for NGC 6717, show a trend that the fainter hot HB stars are dominated in the relatively metal-poor clusters while the relatively metal-rich clusters contain the brighter HB stars. It is suggestive that NGC 6717 would be an extreme example of the second-parameter phenomenon for the bulge globular clusters.

  18. Targeting autocrine HB-EGF signaling with specific ADAM12 inhibition using recombinant ADAM12 prodomain (United States)

    Miller, Miles A.; Moss, Marcia L.; Powell, Gary; Petrovich, Robert; Edwards, Lori; Meyer, Aaron S.; Griffith, Linda G.; Lauffenburger, Douglas A.


    Dysregulation of ErbB-family signaling underlies numerous pathologies and has been therapeutically targeted through inhibiting ErbB-receptors themselves or their cognate ligands. For the latter, “decoy” antibodies have been developed to sequester ligands including heparin-binding epidermal growth factor (HB-EGF); however, demonstrating sufficient efficacy has been difficult. Here, we hypothesized that this strategy depends on properties such as ligand-receptor binding affinity, which varies widely across the known ErbB-family ligands. Guided by computational modeling, we found that high-affinity ligands such as HB-EGF are more difficult to target with decoy antibodies compared to low-affinity ligands such as amphiregulin (AREG). To address this issue, we developed an alternative method for inhibiting HB-EGF activity by targeting its cleavage from the cell surface. In a model of the invasive disease endometriosis, we identified A Disintegrin and Metalloproteinase 12 (ADAM12) as a protease implicated in HB-EGF shedding. We designed a specific inhibitor of ADAM12 based on its recombinant prodomain (PA12), which selectively inhibits ADAM12 but not ADAM10 or ADAM17. In endometriotic cells, PA12 significantly reduced HB-EGF shedding and resultant cellular migration. Overall, specific inhibition of ligand shedding represents a possible alternative to decoy antibodies, especially for ligands such as HB-EGF that exhibit high binding affinity and localized signaling. PMID:26477568

  19. Hb A1c Separation by High Performance Liquid Chromatography in Hemoglobinopathies

    Directory of Open Access Journals (Sweden)

    Vani Chandrashekar


    Full Text Available Hb A1c measurement is subject to interference by hemoglobin traits and this is dependent on the method used for determination. In this paper we studied the difference between Hb A1c measured by HPLC in hemoglobin traits and normal chromatograms. We also studied the correlation of Hb A1c with age. Hemoglobin analysis was carried out by high performance liquid chromatography. Spearman’s rank correlation was used to study correlation between A1c levels and age. Mann-Whitney U test was used to study the difference in Hb A1c between patients with normal hemoglobin and hemoglobin traits. A total of 431 patients were studied. There was positive correlation with age in patients with normal chromatograms only. No correlation was seen in Hb E trait or beta thalassemia trait. No significant difference in Hb A1c of patients with normal chromatograms and patients with hemoglobin traits was seen. There is no interference by abnormal hemoglobin in the detection of A1c by high performance liquid chromatography. This method cannot be used for detection of A1c in compound heterozygous and homozygous disorders.

  20. Understanding the new HbA1c units for the diagnosis of Type 2 diabetes. (United States)

    Braatvedt, Geoff D; Cundy, Tim; Crooke, Michael; Florkowski, Chris; Mann, Jim I; Lunt, Helen; Jackson, Rod; Orr-Walker, Brandon; Kenealy, Timothy; Drury, Paul L


    In New Zealand laboratories the measurement of glycated haemoglobin (HbA1c) for diagnosis of diabetes is now only reported in SI units of mmol/mol. HbA1c is now recommended as the preferred test to diagnose diabetes in most circumstances. The requirement for a second positive test in asymptomatic individuals is retained. An HbA1c greater than and equal to 50 mmol/mol (repeated on a second occasion in asymptomatic patients) is diagnostic of diabetes and a value less than and equal to 40 mmol/mol represents normal glucose tolerance. For patients with an initial HbA1c result of 41-49 mmol/mol, cardiovascular risk assessment and lifestyle interventions are recommended with repeat HbA1c screening in 6-12 months. For patients whose HbA1c is less than and equal to 40 mmol/mol, repeat screening (including for CVD risk) at intermittent intervals is recommended as per published guidelines.

  1. Expression of PRB, FKBP52 and HB-EGF relating with ultrasonic evaluation of endometrial receptivity.

    Directory of Open Access Journals (Sweden)

    Ning Wang

    Full Text Available BACKGROUND: To explore the molecular basis of the different ultrasonic patterns of the human endometrium, and the molecular marker basis of local injury. METHODOLOGY/PRINCIPAL FINDINGS: The mRNA and protein expression of FKBP52, progesterone receptor A (PRA, progesterone receptor B (PRB, and HB-EGF were detected in different patterns of the endometrium by real-time RTPCR and immunohistochemistry. There were differences in the mRNA and protein expression of FKBP52, PRB, and HB-EGF in the triple line (Pattern A and homogeneous (Pattern C endometrium in the window of implantation. No difference was detected in PRA expression. After local injury, the mRNA expression of HB-EGF significantly increased. In contrast, there was no difference in the mRNA expression of FKBP52, PRB, or PRA. The protein expression of FKBP52, PRB, and HB-EGF increased after local injury. There was no difference in the PRA expression after local injury. CONCLUSIONS: PRB, FKBP52, and HB-EGF may be the molecular basis for the classification of the ultrasonic patterns. HB-EGF may be the molecular basis of local injury. Ultrasonic evaluation on the day of ovulation can be effective in predicting the outcome of implantation.

  2. Avaliação de Hb A2 e Hb F em doadores de sangue de região malarígena da Amazônia Oriental brasileira por HPLC Evaluation of Hb A2 and Hb F by HPLC in blood donors from the malaria endemic region of Eastern Amazon of Brazil

    Directory of Open Access Journals (Sweden)

    Wanessa C. Souza


    Full Text Available In malaria endemic regions of Africa, resistance to infection by Plasmodium has been observed in under 6-month-old children, when there are higher fetal hemoglobin (Hb F levels. Research performed in the São José do Rio Preto region, central-east Brazil, reported increased levels of Hb F in blood donors. The purpose of this work was to evaluate the A2 hemoglobin (Hb A2 and Hb F concentrations in blood donors deriving from the Brazilian malaria endemic region. Forty-five blood donor samples from Macapá, from patients with varying genders, ages and ethnic origins, were collected by venous puncture after informed consent was obtained. The samples were analyzed by High Performance Liquid Chromatography (HPLC - System Variant (Bio-Rad. The HPLC demonstrated sensitivity and rapidity in the identification and measurement of the hemoglobins and gave precise results. Moreover, it provided measurement of hemoglobin variants, even when they were present in small amounts, providing a diagnosis of hemoglobinopathies. Hb F levels above the normal were observed in 33.3% of the analyzed samples. The presence of increased Hb F can suggest resistance to infection by Plasmodium falciparum, as there have been reports that infected red blood cells interfere in the development of the parasite.

  3. Clinical, Hematological and Molecular Analysis of Homozygous Hb E (HBB: c.79G > A) in the Indian Population. (United States)

    Jayasree, Divya; Shaji, Ramachandran V; George, Biju; Mathews, Vikram; Srivastava, Alok; Edison, Eunice S


    Homozygous Hb E [β26(B8)Glu→Lys; HBB: c.79G > A] is a clinically mild disease with no significant symptoms. Very few studies are available on clinical variability in Hb E disorders. We report the profile of a series of homozygous Hb E patients in the Indian population. We analyzed various genetic factors that contribute to the heterogeneity in the phenotype of homozygous Hb E patients. Analysis of these parameters further enhances our understanding of the Hb E syndrome.

  4. Frequency and epitope specificity of anti-factor VIII C1 domain antibodies in acquired and congenital hemophilia A. (United States)

    Kahle, Joerg; Orlowski, Aleksander; Stichel, Diana; Healey, John F; Parker, Ernest T; Jacquemin, Marc; Krause, Manuela; Tiede, Andreas; Schwabe, Dirk; Lollar, Pete; Königs, Christoph


    Several studies showed that neutralizing anti-factor VIII (anti-fVIII) antibodies (inhibitors) in patients with acquired hemophilia A (AHA) and congenital hemophilia A (HA) are primarily directed to the A2 and C2 domains. In this study, the frequency and epitope specificity of anti-C1 antibodies were analyzed in acquired and congenital hemophilia inhibitor patients (n = 178). The domain specificity of antibodies was studied by homolog-scanning mutagenesis (HSM) with single human domain human/porcine fVIII proteins and antibody binding to human A2, C1, and C2 domains presented as human serum albumin (HSA) fusion proteins. The analysis with HSA-fVIII domain proteins confirmed the results of the HSM approach but resulted in higher detection levels. The higher detection levels with HSA-fVIII domain proteins are a result of antibody cross-reactivity with human and porcine fVIII leading to false-negative HSM results. Overall, A2-, C1-, and C2-specific antibodies were detected in 23%, 78%, and 68% of patients with AHA (n = 115) and in 52%, 57%, and 81% of HA inhibitor patients (n = 63). Competitive binding of the human monoclonal antibody (mAb) LE2E9 revealed overlapping epitopes with murine C1-specific group A mAbs including 2A9. Mutational analyses identified distinct crucial binding residues for LE2E9 (E2066) and 2A9 (F2068) that are also recognized by anti-C1 antibodies present in patients with hemophilia. A strong contribution of LE2E9- and 2A9-like antibodies was particularly observed in patients with AHA. Overall, our study demonstrates that the C1 domain, in addition to the A2 and C2 domains, contributes significantly to the humoral anti-fVIII immune response in acquired and congenital hemophilia inhibitor patients. © 2017 by The American Society of Hematology.

  5. Dry-heat treatment process for enhancing viral safety of an antihemophilic factor VIII concentrate prepared from human plasma. (United States)

    Kim, In Seop; Choi, Yong Woon; Kang, Yong; Sung, Hark Mo; Shin, Jeong Sup


    Viral safety is a prerequisite for manufacturing clinical antihemophilic factor VIII concentrates from human plasma. With particular regard to the hepatitis A virus (HAV), a terminal dry-heat treatment (100 degrees for 30 min) process, following lyophilization, was developed to improve the virus safety of a solvent/detergent-treated antihemophilic factor VIII concentrate. The loss of factor VIII activity during dry-heat treatment was of about 5%. No substantial changes were observed in the physical and biochemical characteristics of the dry-heat-treated factor VIII compared with those of the factor VIII before dry-heat treatment. The dry-heat-treated factor VIII was stable for up to 24 months at 4oC. The dry-heat treatment after lyophilization was an effective process for inactivating viruses. The HAV, murine encephalomyocarditis virus (EMCV), and human immunodeficiency virus (HIV) were completely inactivated to below detectable levels within 10 min of the dry-heat treatment. Bovine herpes virus (BHV) and bovine viral diarrhea virus (BVDV) were potentially sensitive to the treatment. However porcine parvovirus (PPV) was slightly resistant to the treatment. The log reduction factors achieved during lyophilization and dry-heat treatment were > or =5.55 for HAV, > or =5.87 for EMCV, > or =5.15 for HIV, 6.13 for BHV, 4.46 for BVDV, and 1.90 for PPV. These results indicate that dry-heat treatment improves the virus safety of factor VIII concentrates, without destroying the activity. Moreover, the treatment represents an effective measure for the inactivation of non-lipid-enveloped viruses, in particular HAV, which is resistant to solvent/detergent treatment.

  6. Complex interaction of Hb Hekinan [alpha27(B8) Glu-Asp] and Hb E [beta26(B8) Glu-Lys] with a deletional alpha-thalassemia 1 in a Thai family. (United States)

    Fucharoen, Supan; Changtrakun, Yossombat; Ratanasiri, Thawalwong; Fucharoen, Goonnapa; Sanchaisuriya, Kanokwan


    Hemoglobin (Hb) Hekinan (alpha27; Glu-Asp) is a rare alpha-chain variant found mainly in Japanese and Chinese whereas Hb E (beta26; Glu-Lys) is common among Southeast Asians. We report a hitherto undescribed condition in which these two variants co-segregate. The proband was a 25-yr-old Thai woman who was encountered with the presence of mild hypochromic microcytosis with Hb 8.2 g/dL, hematocrit (Hct) 26.0%, Mean Corpuscular Value (MCV) 68.6 fL, Mean Corpuscular Hemoglobin (MCH) 21.6 pg and Mean Corpuscular Hemoglobin Concentration (MCHC) 31.5 g/dL. Although Hb electrophoresis at alkaline pH did not show any abnormal band except Hb E in addition to Hb A, high performance liquid chromatography analysis revealed abnormal peaks at the Hb A and Hb E positions. DNA analysis of the proband revealed a GAG-GAT mutation at codon 27 of the minor alpha1-globin gene for Hb Hekinan in trans to the South-east Asian (SEA) deletional alpha-thalassemia 1 determinant and a GAG-AAG mutation at codon 26 of the beta-globin gene for Hb E. She was therefore a triple heterozygote for these three anomalies. Family study identified that her mother was a double heterozygote for Hb Hekinan and Hb E without alpha-thalassemia whereas her father was a classical Hb H disease patient. The genotype-phenotype relationship observed in this Thai family with complex hemoglobinopathies is presented and a simple DNA assay based on the polymerase chain reaction methodology for rapid diagnosis of Hb Hekinan is described.

  7. Description of Three New α Variants and Four New β Variants: Hb Montluel [α110(G17)Ala → Val; HBA1: c.332C > T], Hb Cap d'Agde [α131(H14)Ser → Cys; HBA2: c.395C > G] and Hb Corsica [α100(G7)Leu → Pro; HBA1: 302T > C]; Hb Nîmes [β104(G6)Arg → Gly; HBB: c.313A > G], Hb Saint Marcellin [β112(G14)Cys → Gly; HBB: c.337T > G], Hb Saint Chamond [β80(EF4)Asn → 0; HBB: c.241_243delAAC] and Hb Dompierre [β29(B11)Gly → Arg; HBB: c.88G > C]. (United States)

    Renoux, Céline; Feray, Cécile; Joly, Philippe; Lacan, Philippe; Francina, Alain


    We present here seven new hemoglobin (Hb) variants identified during routine Hb analysis. All of them are caused by a missense mutation except Hb Saint Chamond, which results from an in-frame deletion of the asparagine residue at β80. All these variants are clinically silent in the heterozygous state but two of them (Hb Cap d'Agde and Hb Dompierre) may be unstable, whereas Hb Nîmes could present a very slightly elevated oxygen affinity. These data are to be confirmed by appropriate biochemical tests.

  8. The Clinical Significance of HbA1c in Operable Chronic Thromboembolic Pulmonary Hypertension.

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    Manuel Jonas Richter

    Full Text Available Glycosylated hemoglobin A1c (HbA1c has been proposed as an independent predictor of long-term prognosis in pulmonary arterial hypertension. However, the clinical relevance of HbA1c in patients with operable chronic thromboembolic pulmonary hypertension (CTEPH remains unknown. The aim of the present study was to investigate the clinical significance of HbA1c as a biomarker in CTEPH.Prospectively, 102 patients underwent pulmonary endarterectomy (PEA in our national referral center between March 2013 and March 2014, of which after exclusion 45 patients were analyzed. HbA1c- levels, hemodynamic and exercise parameters were analyzed prior and one-year post-PEA.45 patients (BMI: 27.3 ± 6.0 kg/m2; age: 62.7 ± 12.3 years with a mean pulmonary arterial pressure (mPAP of 43.6 ± 9.4 mmHg, a pulmonary vascular resistance (PVR of 712.1 ± 520.4 dyn*s/cm5, a cardiac index (CI of 2.4 ± 0.5 l/min/m2 and a mean HbA1c-level of 39.8 ± 5.6 mmol/mol were included. One-year post-PEA pulmonary hemodynamic and functional status significantly improved in our cohort. Baseline HbA1c-levels were significantly associated with CI, right atrial pressure, peak oxygen uptake and the change of 6-minute walking distance using linear regression analysis. However, using logistic regression analysis baseline HbA1c-levels were not significantly associated with residual post-PEA PH.This is the first prospective study to describe an association of HbA1c-levels with pulmonary hemodynamics and exercise capacity in operable CTEPH patients. Our preliminary results indicate that in these patients impaired glucose metabolism as assessed by HbA1c is of clinical significance. However, HbA1c failed as a predictor of the hemodynamic outcome one-year post-PEA.

  9. HbA1c Test as a Tool in the Diagnosis of Gestational Diabetes Mellitus.

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    Paula Breitenbach Renz

    Full Text Available Gestational diabetes mellitus (GDM is a prevalent and potentially serious condition which may put both mothers and neonates at risk. The current recommendation for diagnosis is the oral glucose tolerance test (OGTT. This study aimed to determine the usefulness of HbA1c test as a diagnostic tool for GDM as compared to the traditional criteria based on the OGTT.This was a diagnostic test accuracy study. We performed OGTT and HbA1c test in women attending prenatal visits at a tertiary hospital. GDM was defined according to WHO1999 or ADA/WHO 2013 criteria. ROC curve was used to evaluate the diagnostic performance of HbA1c. Sensitivity, specificity and likelihood ratios for different HbA1c cut-off points were calculated.Of the 262 women in the third trimester of gestation enrolled in the study, 86 (33% were diagnosed with GDM. Only five of these women presented HbA1c ≥48 mmol/mol (6.5%. This cut-off point presented 100% specificity but very low sensitivity (7%. Based on ROC curve, and considering OGTT as the reference criterion, HbA1c ≥40 mmol/mol (5.8% showed adequate specificity in diagnosing GDM (94.9% but low sensitivity (26.4%. Unlike, HbA1c values of 31 mmol/mol (5.0% presented adequate sensitivity (89.7% but low specificity (32.6% to detect GDM. For women with HbA1c ≥40 mmol/mol (5.8%, the positive and negative likelihood ratios were 5.14 (95%CI 2.49-10.63 and 0.78 (0.68-0.88, respectively. The post-test probability of GDM was about 40%, representing a 4.0-fold increase in the mean pre-test probability. This cut-off point could eliminate the need for the unpleasant and laborious OGTT tests in almost one third of cases, as 38% of patients with GDM may be diagnosable by HbA1c test alone.Our results show that combined HbA1c and OGTT measurements may be useful in diagnosing GDM.

  10. HbA1c for diagnosis and prognosis of gestational diabetes mellitus. (United States)

    Kwon, Soon Sung; Kwon, Ja-Young; Park, Yong-Won; Kim, Young-Han; Lim, Jong-Baeck


    HbA1c is a widely used marker in diagnosing type 2 diabetes mellitus (DM), but its clinical utility in diagnosing gestational diabetes mellitus (GDM) is not established. Here, we evaluated the clinical usefulness of HbA1c in diagnosing GDM and predicting the risk of future type 2 DM development among GDM patients. This retrospective, cross-sectional study included 321 subjects who underwent 100-g oral glucose tolerance tests (OGTT) during pregnancy. HbA1c and other variables were analyzed to evaluate their diagnostic performance for GDM. To evaluate the clinical usefulness of HbA1c in predicting future type 2 DM development, we classified GDM subjects who had more than 3 months of follow-up data into two subgroups: those who developed postpartum type 2 DM (PDM) and those who did not. HbA1c was significantly higher in the GDM group than in the normal control group. With the 100-g OGTT as reference, HbA1c showed 91.3% sensitivity and 62% specificity at a cut-off value of 5.05% (32 mmol/mol) for GDM diagnosis. At a cut-off value of 5.25% (34 mmol/mol), sensitivity was 73.6% and specificity was 77.2%. HbA1c levels during pregnancy were higher in those with PDM than in those without PDM (5.91 [41 mmol/mol] vs. 5.44% [36 mmol/mol], p<0.001). The prognostic value of HbA1c for PDM was evaluated by ROC curve analysis, with sensitivity of 78.6% and specificity of 72.5% at a cut-off value of 5.55% (37 mmol/mol). HbA1c showed high sensitivity with relatively low specificity for diagnosis of GDM in pregnant women and was a potential predictor of PDM. HbA1c may be able to be used as a simple and less invasive alternative screening test for OGTT in GDM patients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. Co-inheritance of the rare β hemoglobin variants Hb Yaounde, Hb Görwihl and Hb City of Hope with other alterations in globin genes: impact in genetic counseling. (United States)

    Vinciguerra, Margherita; Passarello, Cristina; Leto, Filippo; Cassarà, Filippo; Cannata, Monica; Maggio, Aurelio; Giambona, Antonino


    Nearly 1183 different molecular defects of the globin genes leading to hemoglobin variants have been identified ( over the past decades. The purpose of this study was to report three cases, never described in the literature, of co-inheritance of three β hemoglobin variants with other alterations in globin genes and to evaluate the clinical significance to conduct an appropriate genetic counseling. We report the molecular study performed in three probands and their families, sampling during the screening program conducted at the Laboratory for Molecular Prenatal Diagnosis of Hemoglobinopathies at Villa Sofia-Cervello Hospital in Palermo, Italy. This work allowed us to describe the co-inheritance of three rare β hemoglobin variants with other alterations in globin genes: the β hemoglobin variant Hb Yaounde [β134(H12)Val>Ala], found for the first time in combination with ααα(anti3.7) arrangement, and the β hemoglobin variants Hb Görwihl [β5(A2)Pro>Ala] and Hb City of Hope [β69(E13)Gly>Ser], found both in association with β(0) -thalassemia. The present work emphasizes the importance of a careful evaluation of the hematological data, especially in cases of atypical hematological parameters, to carry out an adequate and complete molecular study and to formulate an appropriate genetic counseling for couples at risk. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Crystal Structure of Human Factor VIII: Implications for the Formation of the Factor IXa-Factor VIIIa Complex

    Energy Technology Data Exchange (ETDEWEB)

    Chi Ki Ngo,J.; Huang, M.; Roth, D.; Furie, B.; Furie, B.


    Factor VIII is a procofactor that plays a critical role in blood coagulation, and is missing or defective in hemophilia A. We determined the X-ray crystal structure of B domain-deleted human factor VIII. This protein is composed of five globular domains and contains one Ca(2+) and two Cu(2+) ions. The three homologous A domains form a triangular heterotrimer where the A1 and A3 domains serve as the base and interact with the C2 and C1 domains, respectively. The structurally homologous C1 and C2 domains reveal membrane binding features. Based on biochemical studies, a model of the factor IXa-factor VIIIa complex was constructed by in silico docking. Factor IXa wraps across the side of factor VIII, and an extended interface spans the factor VIII heavy and light chains. This model provides insight into the activation of factor VIII and the interaction of factor VIIIa with factor IXa on the membrane surface.

  13. Crystal Structure of Human Factor VIII: Implications for the Formation of the Factor IXa-Factor VIIIa Complex

    Energy Technology Data Exchange (ETDEWEB)

    Ngo, J.C.; Huang, M.; Roth, D.A.; Furie, B.C.; Furie, B. (Wyeth); (MBL)


    Factor VIII is a procofactor that plays a critical role in blood coagulation, and is missing or defective in hemophilia A. We determined the X-ray crystal structure of B domain-deleted human factor VIII. This protein is composed of five globular domains and contains one Ca{sup 2+} and two Cu{sup 2+} ions. The three homologous A domains form a triangular heterotrimer where the A1 and A3 domains serve as the base and interact with the C2 and C1 domains, respectively. The structurally homologous C1 and C2 domains reveal membrane binding features. Based on biochemical studies, a model of the factor IXa-factor VIIIa complex was constructed by in silico docking. Factor IXa wraps across the side of factor VIII, and an extended interface spans the factor VIII heavy and light chains. This model provides insight into the activation of factor VIII and the interaction of factor VIIIa with factor IXa on the membrane surface.

  14. A Family with γ-Thalassemia and High Hb A2 Levels. (United States)

    Parmeggiani, Giulia; Gualandi, Francesca; Selvatici, Rita; Rimessi, Paola; Bigoni, Stefania; Taddei Masieri, Marina; Dolcini, Bernadetta; Venturoli, Anna; Cappabianca, Maria P; Ferlini, Alessandra; Ravani, Anna


    We describe a family carrying a γ-globin gene deletion associated with an increase of Hb A2 level beyond the normal range. The family included the proband, his sister and their father, all with increased Hb A2 and normal Hb F levels. The proband and his sister showed borderline values of mean corpuscular volume (MCV) and reduced values of mean corpuscular hemoglobin (Hb) (MCH). The proband was referred to our Medical Genetics Service for preconception counseling together with his partner, a typical β-thalassemia (β-thal) carrier. The results were negative for the most frequent α-thalassemia (α-thal) mutations, and had no significant sequence variations of the coding sequences and promoter of the β- and δ-globin genes. Quantitative analysis by multiplex ligation-dependent probe amplification (MPLA) of the β-globin gene cluster detected a heterozygous deletion, ranging between 2.1 and 4.7 kb, in the proband, his sister and the father. The deletion involved the (G)γ gene and (G)γ-(A)γ intergenic region, whereas the 3' region of the (A)γ gene was preserved. A subsequent gap-polymerase chain reaction (gap-PCR) showed that a hybrid (GA)γ fusion gene was present. The deletion segregated with the elevation of Hb A2. The MLPA analysis of the β-globin gene cluster in 150 control alleles excluded a common polymorphism. Despite stronger evidence being needed, the described family suggests a possible role of this γ-globin gene deletion in contributing to Hb A2 elevation, possibly by altering the transcription regulation of the cluster. We propose γ-globin gene dosage analysis to be performed in patients with unexplained elevated Hb A2 levels.

  15. Serum testosterone levels of HbSS (sickle cell disease male subjects in Lagos, Nigeria

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    Adediran Adewumi


    Full Text Available Abstract Background Infertility is a major problem in sickle cell disease patients, especially in males. In addition to low serum testosterone, other abnormalities involving the accessory sex organs, such as the seminal vesicles and the prostate gland, as well as marked decrease in ejaculate volume may be observed in male HbSS patients. Hence, the need to study the role of sex hormones as a cause of infertility in male HbSS patients. Methods An unmatched case-control study was performed using seventy-five consenting subjects from Lagos University Teaching Hospital. These included 47 patients with haemoglobin phenotype SS from the Sickle cell clinic and 28 volunteered medical students and members of staff with haemoglobin phenotype AA. Demographic data were obtained using a self-administered questionnaire. A total of 5 mls of blood was collected from each subject between 9.00 am &, and assayed for serum testosterone concentration. Results The concentrations of serum testosterone in HbSS patients ranged from 0.2 to 4.3 ng/ml with a mean of 1.28 ± 0.72 ng/ml whilst the values in HbAA controls ranged from 1.2 to 6.9 ng/ml with a mean of 2.63 ± 1.04 ng/ml. Seven (25.0% of the 28 controls had serum testosterone concentration lower than the quoted reference (normal range whereas 44 (93.6% of the 47 HbSS subjects had serum testosterone concentration lower than the reference range. Conclusion Overall, subjects with HbSS have significantly lower mean serum testosterone than HbAA controls.

  16. Analysis of inversions in the factor VIII gene in Spanish hemophilia A patients and families

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    Domenech, M.; Tizzano, E.; Baiget, M. [Hospital de Sant Pau, Barcelona (Spain); Altisent, C. [Hospital Vall d`Hebron, Barcelona (Spain)


    Intron 22 is the largest intron of the factor VIII gene and contains a CpG island from which two additional transcripts originate. One of these transcripts corresponds to the F8A gene which have telomeric extragenic copies in the X chromosome. An inversion involving homologous recombination between the intragenic and the distal or proximal copies of the F8A gene has been recently described as a common cause of severe hemophilia A (HA). We analyzed intron 22 rearrangements in 195 HA patients (123 familial and 72 sporadic cases). According to factor VIII levels, our sample was classified as severe in 114 cases, moderate in 29 cases and mild in 52 cases. An intron 22 (F8A) probe was hybridized to Southern blots of BcII digested DNA obtained from peripheral blood. A clear pattern of altered bands identifies distal or proximal inversions. We detected an abnormal pattern identifying an inversion in 49 (25%) of the analyzed cases. 43% of severe HA patients (49 cases) showed an inversion. As expected, no inversion was found in the moderate and mild group of patients. We found a high proportion (78%) of the distal rearrangement. From 49 identified inversions, 33 were found in familial cases (27%), while the remaining 15 were detected in sporadic patients (22%) in support that this mutational event occurs with a similar frequency in familial or sporadic cases. In addition, we detected a significant tendency of distal inversion to occur more frequently in familial cases than in sporadic cases. Inhibitor development to factor VIII was documented in approximately 1/3 of the patients with inversion. The identification of such a frequent molecular event in severe hemophilia A patients has been applied in our families to carrier and prenatal diagnosis, to determine the origin of the mutation in the sporadic cases and to detect the presence of germinal mosaicism.


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    Venny Agustiani Mahardikawati


    Full Text Available 800x600 Normal 0 false false false IN X-NONE X-NONE MicrosoftInternetExplorer4 Quality of human resources is very important to improve productivity. The worker productivity is correlated with nutritional status and health status. The objective of the research is to analyze physical activity, energy intake, nutritional status, of women workers at Tea Plantation PTPN VIII Bandung, West Java. The cross sectional design was used in this study to elaborate physical activity, nutritional status, and productivity of tea picker’s women. The criteria of study sample were tea picker’s women at cluster area of Malabar tea plantation of PTPN VIII Bandung, having infant and they were willing to be interviewed. The total number of 92 women sample was chosen randomly. Primary data consisted of physical activity recall (2x24 hours, food consumption recall (2x24 hours, anthropometry data (weight and height, and productivity (passage of tea sprout. Secondary data were included data of PT Perkebunan Nusantara VIII Bandung, West Java. The result showed that more than a half of samples having active or moderate physical activity level (PAL. The physical activity level of samples during work day (average PAL=1.87 was higher than holiday (average PAL=1.69 (p2362 kcal and 2134 kcal. The average energy adequacy level during workday and day off according to Schofield and Oxford equation were not significantly different, respectively 97,2% and 103,3%. The majority of samples had normal nutritional status, and 30.4% of the sample was overweight. The energy adequacy level according to Schofield and Oxford equation are related to nutritional status of women workers. Keywords: physical activity, energy expenditure, nutritional status, plantation women


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    Djumikasih Djumikasih


    Full Text Available Abstract This paper aims to identify and analyze what the juridical implications of the publication of the decision of the Constitutional Court No. 46/PUU-VIII / 2010 on Child Outside Marriage Deed which has been published by the Department of Population and Civil Registration prior to the establishment of the Constitutional Court's decision . The method used in this study is a normative juridical approach legislation. From the discussion, it can be concluded that the Constitutional Court 46/PUU-VIII/2010 Number of Tests on Article 43 paragraph ( 1 Marriage Act ( Act No. 1 of 1974 when viewed from the angle of legal certainty it will lead to legal certainty . But the decision will not have any juridical implications of the child's birth certificate that has been published outside of marriage and illegitimate child who was born before the date of February 17, 2012, as if enacted would be contrary to the principle of legality is interpreted Article 47 of the Law on the Constitutional Court and Article 28 ( i of the 1945 Constitution . Likewise, if the terms of the fairness and usefulness , especially for justice seekers / applicant , the timing of this decision is not fair and not useful , because although the Court granted the petition but the Constitutional Court can not be applied to her .   Key words: yuridical implication, birth certificate, children who are born outside of marriage   Abstrak   Tulisan ini bertujuan untuk mengetahui dan menganalisis apa implikasi yuridis dari terbitnya putusan MK Nomor 46/PUU-VIII/ 2010 terhadap Akta Anak Luar Kawin yang sudah diterbitkan oleh Dinas Kependudukan dan Catatan Sipil sebelum lahirnya putusan MK tersebut. Metode yang digunakan dalam penelitian ini adalah yuridis normative dengan pendekatan perundang-undangan. Dari pembahasan dapat disimpulkan bahwa Putusan MK Nomer 46/PUU-VIII/2010 tentang Pengujian terhadap Pasal 43 ayat (1 UU Perkawinan (UU NO 1 Tahun 1974 jika dilihat dari sudut kepastian

  19. Underground Test Area Subproject Phase I Data Analysis Task. Volume VIII - Risk Assessment Documentation Package

    Energy Technology Data Exchange (ETDEWEB)



    Volume VIII of the documentation for the Phase I Data Analysis Task performed in support of the current Regional Flow Model, Transport Model, and Risk Assessment for the Nevada Test Site Underground Test Area Subproject contains the risk assessment documentation. Because of the size and complexity of the model area, a considerable quantity of data was collected and analyzed in support of the modeling efforts. The data analysis task was consequently broken into eight subtasks, and descriptions of each subtask's activities are contained in one of the eight volumes that comprise the Phase I Data Analysis Documentation.

  20. Comercio Internacional mediterráneo en el siglo VIII a.C.

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    Paloma Cabrera Bonet


    Full Text Available The VIII century B.C. saw, for the first time after the breakdown of the system in the Late Bronze Age, the revival of a true intemational trade at a growing scale, especíally protagonized by Phoenicians and Greeks. In this article we analyze sorne aspects of this phenomenon, from the Aegean to the Far West, which made possíble, through a vaste network of trading routes, a large multinational ínteractíon. We understand the international trade as a key factor in the proccess of economic, social and political changes of the Mediterranean areas submerged in this complex "world-system".

  1. Production of Lentiviral Vectors Encoding Recombinant Factor VIII Expression in Serum-Free Suspension Cultures

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    Angelo Luis Caron


    Full Text Available ABSTRACT Lentiviral vector-mediated gene transfer offers several advantages over other gene delivery vectors when considering gene and cell therapy applications. However, using these therapies in clinical applications involves large-scale vector production in an efficient and cost-effective manner. Here we describe a high yield production of a lentivirus encoding recombinant factor VIII in a scalable and GMP-compliant culture system, based on serum free suspension cultures and transient transfection with an inexpensive reagent, polyethylenimine (PEI, reaching a total viral yield of 2.48x108 particles.

  2. Measurements of Sheath Currents and Equilibrium Potential on the Explorer VIII Satellite (1960 xi) (United States)

    Bourdeau, R. E.; Donley, J. L.; Serbu, G. P.; Whipple, E. C., Jr.


    Experimental data were obtained from the Explorer VIII satellite on five parameters pertinent to the problem of the interaction of space vehicles with an ionized atmosphere. The five parameters are: photoemission current due to electrons emitted from the satellite surfaces as a result of solar radiation; electron and positive ion currents due to the diffusion of charged particles from the medium to the spacecraft; the vehicle potential relative to the medium, and the ambient electron temperature. Included in the experimental data is the aspect dependence of the photoemission and diffusion currents. On the basis of the observations, certain characteristics of the satellite's plasma sheath are postulated.

  3. Physiological properties and genome structure of the hyperthermophilic filamentous phage φOH3 which infects Thermus thermophilus HB8

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    Yuko eNagayoshi


    Full Text Available A filamentous bacteriophage, φOH3, was isolated from hot spring sediment in Obama hot spring in Japan with the hyperthermophilic bacterium Thermus thermophilus HB8 as its host. Phage φOH3, which was classified into the Inoviridae family, consists of a flexible filamentous particle 830 nm long and 8 nm wide. φOH3 was stable at temperatures ranging from 70 to 90 °C and at pHs ranging from 6 to 9. A one-step growth curve of the phage showed a 60-min latent period beginning immediately postinfection, followed by intracellular virus particle production during the subsequent 40 min. The released virion number of φOH3 was 109. During the latent period, both single stranded DNA (ssDNA and the replicative form (RF of phage DNA were multiplied from min 40 onward. During the release period, the copy numbers of both ssDNA and RF DNA increased sharply. The size of the φOH3 genome is 5,688 bp, and 8 putative open reading frames (ORFs were annotated. These ORFs were encoded on the plus strand of RF DNA and showed no significant homology with any known phage genes, except ORF 5, which showed 60% identity with the gene VIII product of the Thermus filamentous phage PH75. All the ORFs were similar to predicted genes annotated in the Thermus aquaticus Y51MC23 and Meiothermus timidus DSM 17022 genomes at the amino acid sequence level. This is the first report of the whole genome structure and DNA multiplication of a filamentous T. thermophilus phage within its host cell.

  4. Identification and Expression Analysis of a Novel HbCIPK2-Interacting Ferredoxin from Halophyte H. brevisubulatum.

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    Chao Zhang

    Full Text Available Ferredoxin is a small iron-sulfer protein involved in various one-eletron transfer pathways. Little is known about how ferredoxin is regulated to distribute electron under abiotic stress. Our previous study has showed that HbCIPK2 conferred salinity and drought tolerance. Thus, we hypothesized that HbCIPK2 could mediate the activities of interacting partners as a signal transducer. In this report, we identified a novel HbCIPK2-interacting ferredoxin (HbFd1 from halophyte Hordeum brevisubulatum by yeast two-hybrid screens, confirmed this interaction by BiFC in vivo and CoIP in vitro, and presented the expression pattern of HbFd1. HbFd1 was down-regulated under salinity and cold stress but up-regulated under PEG stress, its expression showed tissue-specific, mainly in shoot chloroplast, belonging to leaf-type subgroup. Moreover, HbCIPK2 could recruit HbFd1 to the nucleus for their interaction. The C-terminal segment in HbFd1 protein was involved in the interaction with HbCIPK2. These results provided insight into the connection between CBL-CIPK signaling network and Fd-dependent metabolic pathways.

  5. Engineering Oxidative Stability in Human Hemoglobin based on the Hb Providence (βK82D) mutation and Genetic Crosslinking. (United States)

    Strader, Michael Brad; Bangle, Rachel; Parker Siburt, Claire J; Varnado, Cornelius L; Soman, Jayashree; Benitez Cardenas, Andres S; Samuel, Premila S; Singleton, Eileen W; Crumbliss, Alvin L; Olson, John S; Alayash, Abdu I


    Previous work suggested that hemoglobin (Hb) tetramer formation slows autoxidation and hemin loss and that the naturally occurring mutant, Hb Providence (βK82D) is much more resistant to degradation by H2O2 We have examined systematically the effects of genetic crosslinking of Hb tetramers with and without the Hb Providence mutation on autoxidation, hemin loss, and reactions with H2O2, using native HbA and various wild-type recombinant Hbs as controls. Genetically crosslinked Hb Presbyterian (βN108K) was also examined as an example of a low oxygen affinity tetramer. Our conclusions are: (a) at low concentrations, all the crosslinked tetramers show smaller rates of autoxidation and hemin loss than HbA, which can dissociate into much less stable dimers and (b) the Hb Providence βK82D mutation confers more resistance to degradation by H2O2, by markedly inhibiting oxidation of the β93 cysteine side chain, particularly in crosslinked tetramers and even in the presence of the destabilizing Hb Presbyterian mutation. These results show that crosslinking and the βK82D mutation do enhance the resistance of Hb to oxidative degradation, a critical element in the design of a safe and effective oxygen therapeutic. ©2017 The Author(s).

  6. Heparin-binding EGF-like growth factor (HB-EGF) promotes cell migration and adhesion via focal adhesion kinase. (United States)

    Su, Yanwei; Besner, Gail E


    Cell migration and adhesion are essential in intestinal epithelial wound healing and recovery from injury. Focal adhesion kinase (FAK) plays an important role in cell-extracellular matrix signal transduction. We have previously shown that heparin-binding EGF-like growth factor (HB-EGF) promotes intestinal epithelial cell (IEC) migration and adhesion in vitro. The present study was designed to determine whether FAK is involved in HB-EGF-induced IEC migration and adhesion. A scrape wound healing model of rat IECs was used to examine the effect of HB-EGF on FAK-dependent cell migration in vitro. Immunofluorescence and Western blot analyses were performed to evaluate the effect of HB-EGF on the expression of phosphorylated FAK (p-FAK). Cell adhesion assays were performed to determine the role of FAK in HB-EGF-induced cell adhesion on fibronectin (FN). HB-EGF significantly increased healing after scrape wounding, an effect that was reversed in the presence of an FAK inhibitor 14 (both with P HB-EGF increased p-FAK expression and induced p-FAK redistribution and actin reorganization in migrating rat IECs. Cell adhesion and spreading on FN were significantly increased by HB-EGF (P HB-EGF-induced cell adhesion and spreading on FN (both with P HB-EGF-mediated IEC migration and adhesion. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Aberrant glycated haemoglobin (HbA1c) results leading to haemoglobinopathy diagnosis in four Belgian patients. (United States)

    Van Laer, C; Harteveld, C L; Pauwels, S; Desmet, K; Kieffer, D


    We report four cases in which haemoglobinopathy screening was triggered following aberrant HbA1c analysis. Either the HbA1c assay was unable to produce a quantifiable result or it showed the presence of an extra fraction and/or the result was discordant with the clinical context. In the reported four patients, all from Caucasian, Belgian descent, Hb analysis was performed using cation-exchange high performance liquid chromatography. If necessary, additional Hb electrophoresis was carried out to establish a preliminary (biochemical) diagnosis. Definitive diagnosis was obtained for every sample through DNA-analysis. Three patients were carriers of Hb J-Toronto and one of Hb Stanleyville-II. This report underlines the importance of correct interpretation of HbA1c results to avoid mismanagement of (diabetic) patients. Since neither the RBC indices, the clinical context, nor the ethnicity of these patients was suspicious for an underlying haemoglobinopathy, the aberrant HbA1c result was the only indicator for further investigation. Laboratory personnel and clinicians should be aware of the possibility of uncommon, sometimes clinically unsuspected, Hb variants to cause aberrant HbA1c values, even in populations with low prevalence for haemoglobinopathies. Further analysis should be prompted to obtain definitive diagnosis. Alternative methods for monitoring glycaemic control should be used.

  8. An alternative approach to modelling HbA1c trajectories in patients with type 2 diabetes mellitus. (United States)

    McEwan, Phil; Bennett, Hayley; Qin, Lei; Bergenheim, Klas; Gordon, Jason; Evans, Marc


    Time-dependent HbA1c trajectories in health economic models of type 2 diabetes mellitus (T2DM) are typically informed by the UK Prospective Diabetes Study (UKPDS). However, this approach may not accurately predict HbA1c progression in patients who do not conform to the demographic profile of the original UKPDS cohort. This study aimed to develop an alternative mathematical model (MM) to simulate HbA1c progression in T2DM. A systematic literature review identified studies, published between 2005 and 2015, that reported HbA1c in adult T2DM patients over a minimum duration of 18 months. Pooled data from eligible studies were used to develop an alternative MM equation for HbA1c progression, which was then contrasted with the UKPDS 68 progression equation in illustrative scenarios. A total of 68 studies were eligible for data extraction (mean follow-up time 4.1 years). HbA1c progression was highly heterogeneous across studies, varying with baseline HbA1c, treatment group and patient age. The MM equation was fitted with parameters for mean baseline HbA1c (8.3%), initial change in HbA1c (-0.62%) and upper quartile of maximum observed HbA1c (9.3%). Differences in HbA1c trajectories between the MM and UKPDS approaches altered the timing of therapy escalation in illustrative scenarios. The MM represents an alternative approach to simulate HbA1c trajectories in T2DM models, as UKPDS data may not adequately reflect the heterogeneity of HbA1c profiles observed in clinical studies. However, the choice of approach should ultimately be determined by the characteristics of individual patients under consideration and the clinical face validity of the modelled trajectories. © 2016 John Wiley & Sons Ltd.

  9. Biochemical and Molecular Analysis of the Hb Lepore Boston Washington in a Syrian Homozygous Child. (United States)

    Pirastru, Monica; Manca, Laura; Trova, Sandro; Mereu, Paolo


    Hemoglobin (Hb) Lepore is composed of two normal α chains and two δβ fusion globins that arise from unequal crossover events between the δ- and β-globin genes. The Hb Lepore is widespread all over the world and in many ethnic groups. It includes some of the few clinically significant Hb variants that are associated with a β-thalassemia phenotype. Here, we describe the first occurrence of Hb Lepore Boston Washington in a Syrian individual. The patient, a 10-year-old child, shows severe anemia with a Hb level of 6.85 g/dL and typical thalassemic red cell indices. The diagnostic procedure implies hematological, biochemical, and molecular analysis, including multiplex ligation-dependent probe amplification (MLPA) assay, GAP-PCR, and DNA sequencing. This latter allowed us to define the correct structure of the hybrid δβ-globin gene. The knowledge of the spectrum of mutations associated with different geographical areas is the prerequisite to set up large-scale screening programs and be able to offer genetic counseling to couples at risk.

  10. Biochemical and Molecular Analysis of the Hb Lepore Boston Washington in a Syrian Homozygous Child

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    Monica Pirastru


    Full Text Available Hemoglobin (Hb Lepore is composed of two normal α chains and two δβ fusion globins that arise from unequal crossover events between the δ- and β-globin genes. The Hb Lepore is widespread all over the world and in many ethnic groups. It includes some of the few clinically significant Hb variants that are associated with a β-thalassemia phenotype. Here, we describe the first occurrence of Hb Lepore Boston Washington in a Syrian individual. The patient, a 10-year-old child, shows severe anemia with a Hb level of 6.85 g/dL and typical thalassemic red cell indices. The diagnostic procedure implies hematological, biochemical, and molecular analysis, including multiplex ligation-dependent probe amplification (MLPA assay, GAP-PCR, and DNA sequencing. This latter allowed us to define the correct structure of the hybrid δβ-globin gene. The knowledge of the spectrum of mutations associated with different geographical areas is the prerequisite to set up large-scale screening programs and be able to offer genetic counseling to couples at risk.

  11. Excess HB-EGF, which promotes VEGF signaling, leads to hydrocephalus (United States)

    Shim, Joon W.; Sandlund, Johanna; Hameed, Mustafa Q.; Blazer-Yost, Bonnie; Zhou, Feng C.; Klagsbrun, Michael; Madsen, Joseph R.


    Heparin binding epidermal growth factor-like growth factor (HB-EGF) is an angiogenic factor mediating radial migration of the developing forebrain, while vascular endothelial growth factor (VEGF) is known to influence rostral migratory stream in rodents. Cell migratory defects have been identified in animal models of hydrocephalus; however, the relationship between HB-EGF and hydrocephalus is unclear. We show that mice overexpressing human HB-EGF with β-galactosidase reporter exhibit an elevated VEGF, localization of β-galactosidase outside the subventricular zone (SVZ), subarachnoid hemorrhage, and ventriculomegaly. In Wistar polycystic kidney rats with hydrocephalus, alteration of migratory trajectory is detected. Furthermore, VEGF infusions into the rats result in ventriculomegaly with an increase of SVZ neuroblast in rostral migratory stream, whereas VEGF ligand inhibition prevents it. Our results support the idea that excess HB-EGF leads to a significant elevation of VEGF and ventricular dilatation. These data suggest a potential pathophysiological mechanism that elevated HB-EGF can elicit VEGF induction and hydrocephalus. PMID:27243144

  12. Two α1-Globin Gene Point Mutations Causing Severe Hb H Disease. (United States)

    Jiang, Hua; Huang, Lv-Yin; Zhen, Li; Jiang, Fan; Li, Dong-Zhi


    Hb H disease is generally a moderate form of α-thalassemia (α-thal) that rarely requires regular blood transfusions. In this study, two Chinese families with members carrying transfusion-dependent Hb H disease were investigated for rare mutations on the α-globin genes (HBA1, HBA2). In one family, Hb Zürich-Albisrieden [α59(E8)Gly→Arg; HBA1: c.178G>C] in combination with the Southeast Asian (- -(SEA)) deletion was the defect responsible for the severe phenotype. In another family, a novel hemoglobin (Hb) variant named Hb Sichuan (HBA1: c.393_394insT), causes α-thal and a severe phenotype when associated with the - -(SEA) deletion. As these two HBA1 mutations can present as continuous blood transfusion-dependent α-thal, it is important to take this point into account for detecting the carriers, especially in couples in which one partner is already a known α(0)-thal carrier.

  13. Hb Presbyterian (HBB: c.327C>G) in a Nicaraguan Family. (United States)

    Pernudy-Ubau, Allan; Salinas-Molina, Jaslyn; Requenez, Yaneris; Ortiz-Lopez, Marianela; Puller, Ann-Christin; García-Rosales, Kenia; Rodríguez-Estrada, Anaishelle; Rodríguez-Romero, Walter; Mejía-Baltodano, Gerardo; Luo, Hong-Yuan; Chui, David H K


    Hemoglobin (Hb) is the protein responsible for oxygen transportation. It is a tetrameric protein comprising two α- and two β-globin subunits. In the literature, a large number of mutations in the α- and β-globin genes have been documented. Among these mutations, Hb Presbyterian (HBB: c.327 C>G), is a naturally occurring mutant exerting low oxygen affinity. The C to G exchange (AAC>AAG) at codon 108 of the β-globin gene results in the substitution of asparagine by lysine. Here, we document the identification of HBB: c.327 C>G in a 6-year-old female patient and her father from Nicaragua and Cuba, respectively. The presence of the abnormal Hb was confirmed by cellulose acetate electrophoresis, high performance liquid chromatography (HPLC) and genomic DNA sequencing. The β-globin gene sequences for both, father and daughter, disclosed the heterozygous mutation at codon 108 to be Hb Presbyterian or HBB: c.327 C>G. The mutant Hb was previously reported in four families from North America, Germany, Japan and Spain, respectively. This is the fifth family carrying HBB: c.327 C>G described to date and the first report from Latin America.

  14. Recent achievements with a cryogenic ultra-lightweighted HB-Cesic mirror (United States)

    Krödel, Matthias R.; Hofbauer, Peter; Devilliers, Christophe; Sodnik, Zoran; Robert, Patrick


    During the past two years, ECM, Germany, together with Mitsubishi Electric Corporation (MELCO), Japan, developed a new carbon-fiber-reinforced SiC material, called HB-Cesic®, which possesses superior mechanical and thermal cryogenic properties compared to traditional Cesic®. This combination makes HB-Cesic® an excellent choice for large cryogenic mirrors, which will be required for future scientific space missions, such as SPICA and DARWIN. ESA contracted Thales Alenia Space (TAS), France, to design a super-lightweighted HB-Cesic® mirror with a diameter of 600 mm, isostatic fixations, and a special astigmatism compensation device (ACD) for mirror shape control. The mirror was manufactured by ECM, polished and coated by Société Européenne de Systèmes Optiques (SESO), France, and tested to cryogenic temperatures by TAS. The measured wave-front error at ambient and cryogenic temperatures demonstrated the excellent homogeneity of HB-Cesic® and TAS' expertise in mirror mounting. Furthermore, when thermally actuated, the ACD exhibited perfect control of the mirror shape. This success confirmed HB-Cesic®'s superior material properties and its applicability to future cryogenic space mirrors. In this paper we describe the design and fabrication process of this cryogenic mirror and give test results at ambient and cryogenic temperatures.

  15. [Assays of HbA1c and Amadori products in human biology]. (United States)

    Gillery, P


    Different Amadori products, formed during the early steps of the non-enzymatic glycation of proteins, may be assayed in current practice in human biology. The most important marker is HbA1c, resulting from the binding of glucose to the N-terminal extremity of HbA beta chains. HbA1c may be evaluated by various techniques (ion exchange or affinity high performance liquid chromatography, capillary electrophoresis, immunoassay, enzymatic technique) and is considered the best marker of diabetic patient survey. Due to its irreversible and cumulative formation, it provides a retrospective information on the glycemic balance over the four to eight weeks preceding blood collection. It benefits from an international standardization, based on a reference method using liquid chromatography coupled to capillary electrophoresis or mass spectrometry, maintained by an international network of reference laboratories. When HbA1c assay cannot be used (anemia, hemolysis, hemoglobinopathy) or when a shorter period of glycemic equilibrium must be evaluated (child and adolescent, pregnancy, therapeutic changes), other Amadori products may be assayed, like plasma fructosamine (all plasma glycated proteins) or glycated albumin. Nevertheless, these assays are less used in practice, because their semiological value has been less evidenced. Besides, fructosamine assay lacks specificity, and glycated albumin assay has been described recently. An expanding use of HbA1c assay is expected, especially for the diagnosis of diabetes mellitus and the evaluation of other risks, especially cardiovascular ones. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  16. Coacervate delivery of HB-EGF accelerates healing of type 2 diabetic wounds. (United States)

    Johnson, Noah R; Wang, Yadong


    Chronic wounds such as diabetic ulcers pose a significant challenge as a number of underlying deficiencies prevent natural healing. In pursuit of a regenerative wound therapy, we developed a heparin-based coacervate delivery system that provides controlled release of heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) within the wound bed. In this study, we used a polygenic type 2 diabetic mouse model to evaluate the capacity of HB-EGF coacervate to overcome the deficiencies of diabetic wound healing. In full-thickness excisional wounds on NONcNZO10 diabetic mice, HB-EGF coacervate enhanced the proliferation and migration of epidermal keratinocytes, leading to accelerated epithelialization. Furthermore, increased collagen deposition within the wound bed led to faster wound contraction and greater wound vascularization. Additionally, in vitro assays demonstrated that HB-EGF released from the coacervate successfully increased migration of diabetic human keratinocytes. The multifunctional role of HB-EGF in the healing process and its enhanced efficacy when delivered by the coacervate make it a promising therapy for diabetic wounds. © 2015 by the Wound Healing Society.


    Directory of Open Access Journals (Sweden)

    Singgih Baswendro


    Full Text Available Artikel ini dibuat berdasarkan penelitian skripsi yang telah dilaksanakan. Tujuan penelitian ini adalah (1 untuk mengetahui hasil kemampuan pemecahan masalah siswa kelas VIII pada materi lingkaran dengan menggunakan model TGT mencapai KKM, dan (2 untuk mengetahui rata-rata kemampuan pemecahan masalah siswa dengan model TGT lebih tinggi daripada dengan model ekspositori. Penelitian ini dilaksanakan di SMP Negeri 3 Ungaran dengan populasi siswa kelas VIII tahun ajaran 2014/2015. Pengambilan kelas sampel menggunakan teknik cluster random sampling. Untuk mengetahui hasil penelitian ini, data hasil akhir diuji dengan uji proporsi dan uji perbedaan rata-rata. Hasil penelitan ini menunjukkan bahwa (1 hasil kemampuan pemecahan masalah siswa kelas VIII pada materi lingkaran dengan menggunakan model TGT mencapai KKM, dan (2 rata-rata kemampuan pemecahan masalah siswa dengan model TGT lebih tinggi daripada dengan model ekspositori. Dengan ini maka model TGT dengan pendekatan scientific berbantuan CD pembelajaran efektif terhadap kemampuan pemecahan masalah siswa.

  18. An integrated framework for joint HRF and drift estimation and HbO/HbR signal improvement in fNIRS data. (United States)

    Shah, Adnan; Seghouane, Abd-Krim


    Nonparametric hemodynamic response function (HRF) estimation in functional near-infrared spectroscopy (fNIRS) data plays an important role when investigating the temporal dynamics of a brain region response during activations. Assuming the drift arising from both physical and physiological effects in fNIRS data is Lipschitz continuous; a novel algorithm for joint HRF and drift estimation is derived in this paper. The proposed algorithm estimates the HRF by applying a first-order differencing to the fNIRS time series samples in order to remove the drift effect. An estimate of the drift is then obtained using a wavelet thresholding technique applied to the residuals generated by removing the estimated induced activation response from the fNIRS time-series. It is shown that the proposed HRF estimator is √N consistent whereas the estimator of the drift is asymptotically optimal. The de-drifted fNIRS oxygenated (HbO) and deoxygenated (HbR) hemoglobin responses are then obtained by removing the corresponding estimated drifts from the fNIRS time-series. Its performance is assessed using both simulated and real fNIRS data sets. The application results reveal that the proposed joint HRF and drift estimation method is efficient both computationally and in terms of accuracy. In comparison to traditional model based methods used for HRF estimation, the proposed novel method avoids the selection of a model to remove the drift component. As a result, the proposed method finds an optimal estimate of the fNIRS drift and offers a model-free approach to de-drift the HbO/HbR responses.

  19. A comparative evaluation of the analytical performances of Capillarys 2 Flex Piercing, Tosoh HLC-723 G8, Premier Hb9210, and Roche Cobas c501 Tina-quant Gen 2 analyzers for HbA1c determination. (United States)

    Wu, Xiaobin; Chao, Yan; Wan, Zemin; Wang, Yunxiu; Ma, Yan; Ke, Peifeng; Wu, Xinzhong; Xu, Jianhua; Zhuang, Junhua; Huang, Xianzhang


    Haemoglobin A1c (HbA1c) is widely used in the management of diabetes. Therefore, the reliability and comparability among different analytical methods for its detection have become very important. A comparative evaluation of the analytical performances (precision, linearity, accuracy, method comparison, and interferences including bilirubin, triglyceride, cholesterol, labile HbA1c (LA1c), vitamin C, aspirin, fetal haemoglobin (HbF), and haemoglobin E (Hb E)) were performed on Capillarys 2 Flex Piercing (Capillarys 2FP) (Sebia, France), Tosoh HLC-723 G8 (Tosoh G8) (Tosoh, Japan), Premier Hb9210 (Trinity Biotech, Ireland) and Roche Cobas c501 (Roche c501) (Roche Diagnostics, Germany). A good precision was shown at both low and high HbA1c levels on all four systems, with all individual CVs below 2% (IFCC units) or 1.5% (NGSP units). Linearity analysis for each analyzer had achieved a good correlation coefficient (R2 > 0.99) over the entire range tested. The analytical bias of the four systems against the IFCC targets was less than ± 6% (NGSP units), indicating a good accuracy. Method comparison showed a great correlation and agreement between methods. Very high levels of triglycerides and cholesterol (≥ 15.28 and ≥ 8.72 mmol/L, respectively) led to falsely low HbA1c concentrations on Roche c501. Elevated HbF induced false HbA1c detection on Capillarys 2FP (> 10%), Tosoh G8 (> 30%), Premier Hb9210 (> 15%), and Roche c501 (> 5%). On Tosoh G8, HbE induced an extra peak on chromatogram, and significantly lower results were reported. The four HbA1c methods commonly used with commercial analyzers showed a good reliability and comparability, although some interference may falsely alter the result.

  20. Effects of a healthier snack on snacking habits and glycated Hb (HbA1c): a 6-week intervention study. (United States)

    Yan, Mary R; Parsons, Andrew; Whalley, Gillian A; Rush, Elaine C


    Dietary behaviour modification may change eating habits and reduce the impact of poor nutrition. This study aimed to evaluate the effects of daily consumption of a healthier snack bar on snacking habits and glycated Hb (HbA1c) within a 6-week intervention. In all, twenty-eight participants were randomly allocated to two groups to either consume the bars as the main snack for 6 weeks (n 14) or receipt of the bars was delayed for 6 weeks (n 14) following a stepped-wedge design. All participants had HbA1c concentrations measured at weeks -1, 0, 4, 6, 10 and 12. A short dietary habits questionnaire was self-completed at weeks 0, 6 and 12. Participants consumed the bars they received instead of other snacks, and found that the healthier snack bar was acceptable as part of their daily dietary pattern. Over the 12 weeks, there was a significant reduction in intake of biscuits, cakes and pies (approximately 2 servings/week, Psnack intervention and a trend towards a favourable effect on glucose homoeostasis. Habitual snacking behaviour has the potential to be improved through changes in the food supply, and in the longer term may reduce the impact of poor nutrition on public health.

  1. Indonesian Interference on English Language in VIII Grade Junior High School Students

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    Agustia Km Tri Sutrisna


    Full Text Available This study aims to determine the type of Indonesian interference found in English language among class VIII SMPK 2 Harapan Untal-Untal students. This research is done by analyzing the result of simple text translation done by the students of class VIII SMPK 2 Harapan Untal-Untal, then from the translation result will be analyzed what kind of interference that appeared. Methods of data collection in this study using observational research methods and literature. The data that have been collected in the form of simple translations from the students will be analyzed descriptively using related theories to find out what kind of interference found in the analysis. Further, in relating to interference, it will find a way out to reduce and even eliminate Indonesian interference itself. The results to be achieved in this research is recognize the level of Indonesian language interference in the use of English among the junior high school students, then find the practical efforts to be done so that interference does not increased. So, the use and English understanding can be done as much as possible. The finding of the paper found that 6 interference such as grammar structure, subject pronoun, adjectives, auxiliaries, preposition and word order.


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    Daroinis Sa’adah


    Full Text Available The objectives of this study are to develop teaching aids, to test the validity and practically teaching aids, and to test the effectiveness of learning process using CORE (Connecting, Organizing, Reflecting, and Extending model with metacognitive approach to improve the ability in Geometri problem solving. This research and development design is adapted from Plomp model by using several phases: (1 preliminary investigation; (2 design; (3 realization/construction; (4 test, evaluation and revision. This study developed some teaching aids; a part of syllabus, lesson plan, students book, students’ work sheet, and test of problem solving ability. The subject of the try out is eighth graders of MTs NU Nurul Huda Kudus. The research data to test the validity, practically, and effectiveness are collected by: (1 validation sheet; (2 observation sheet; (3 problem solving test. The results of research showed that development teaching aids using CORE model with metacognitive approach for Geometry material of VIII grade is valid and practical, and learning CORE model with metacognitive approach for Geometry material of VIII grade is effective.

  3. Innovative Approaches for Immune Tolerance to Factor VIII in the Treatment of Hemophilia A

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    Alexandra Sherman


    Full Text Available Hemophilia A (coagulation factor VIII deficiency is a debilitating genetic disorder that is primarily treated with intravenous replacement therapy. Despite a variety of factor VIII protein formulations available, the risk of developing anti-dug antibodies (“inhibitors” remains. Overall, 20–30% of patients with severe disease develop inhibitors. Current clinical immune tolerance induction protocols to eliminate inhibitors are not effective in all patients, and there are no prophylactic protocols to prevent the immune response. New experimental therapies, such as gene and cell therapies, show promising results in pre-clinical studies in animal models of hemophilia. Examples include hepatic gene transfer with viral vectors, genetically engineered regulatory T cells (Treg, in vivo Treg induction using immune modulatory drugs, and maternal antigen transfer. Furthermore, an oral tolerance protocol is being developed based on transgenic lettuce plants, which suppressed inhibitor formation in hemophilic mice and dogs. Hopefully, some of these innovative approaches will reduce the risk of and/or more effectively eliminate inhibitor formation in future treatment of hemophilia A.

  4. The head that wears the crown: Henry VIII and traumatic brain injury. (United States)

    Ikram, Muhammad Qaiser; Sajjad, Fazle Hakim; Salardini, Arash


    Henry VIII of England is one of the most controversial figures in European history. He was born on 28 June 1491 as the second son of Henry VII and Elizabeth of York and became the heir to the English throne after his elder brother died prematurely. A contradictory picture of Henry's character emerges from history: the young Henry was a vigorous, generous and intelligent king who saw early military and naval successes. In contrast, in his later years he became cruel, petty and tyrannical. His political paranoia and military misjudgements are in direct contrast to his earlier successes and promise. Several hypotheses have been put forward regarding his transformation from a renaissance king to a later medieval tyrant, including endocrinopathies, psychiatric illnesses and traumatic brain injury. In this paper we examine the historical evidence linking the change in Henry's personality and health problems to traumatic brain injury. To our knowledge this is the first systematic neurological study of traumatic brain injury in Henry VIII. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Detection of Fibrinogen and Coagulation Factor VIII in Plasma by a Quartz Crystal Microbalance Biosensor

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    Chunyan Yao


    Full Text Available A quartz crystal microbalance (QCM biosensor with nanogram sensitivity has been constructed through a reasonable designing and biological processing of the piezoelectric quartz crystals. Due to its highly sensitivity, real time detection and low cost, the proposed QCM biosensor has a promising potential in blood coagulation research. In the current study, the QCM biosensor was used to determine the activated partial thromboplastin time (APTT for 120 anticoagulated plasma specimens. A good linear relationship was found in a double-logarithmic plot of APTT versus fibrinogen concentration in the range of 1.58–6.30 g/L. For factor VIII, the detection range by the QCM biosensor is 0.0185–0.111 mg/L. The QCM biosensor results were compared with those obtained by commercial optical coagulometry and a good agreement (correlation coefficient is 0.949 for fibrinogen, and 0.948 for factor VIII was reached. Furthermore, the QCM determination can be completed within 10 min. Our study suggested that the proposed QCM biosensor could provide for more convenient and time saving operations, which may be useful in clinical situations for rapid monitoring of anticoagulant therapy using small volume (20 μL plasma specimens.

  6. Improving attitudes toward mathematics learning with problem posing in class VIII (United States)

    Vionita, Alfha; Purboningsih, Dyah


    This research is classroom action research which is collaborated to improve student's behavior toward math and mathematics learning at class VIII by using problem posing approach. The subject of research is all of students grade VIIIA which consist of 32 students. This research has been held on two period, first period is about 3 times meeting, and second period is about 4 times meeting. The instrument of this research is implementation of learning observation's guidance by using problem posing approach. Cycle test has been used to measure cognitive competence, and questionnaire to measure the students' behavior in mathematics learning process. The result of research shows the students' behavior has been improving after using problem posing approach. It is showed by the behavior's criteria of students that has increasing result from the average in first period to high in second period. Furthermore, the percentage of test result is also improve from 68,75% in first period to 78,13% in second period. On the other hand, the implementation of learning observation by using problem posing approach has also improving and it is showed by the average percentage of teacher's achievement in first period is 89,2% and student's achievement 85,8%. These results get increase in second period for both teacher and students' achievement which are 94,4% and 91,11%. As a result, students' behavior toward math learning process in class VIII has been improving by using problem posing approach.

  7. Innovative Approaches for Immune Tolerance to Factor VIII in the Treatment of Hemophilia A (United States)

    Sherman, Alexandra; Biswas, Moanaro; Herzog, Roland W.


    Hemophilia A (coagulation factor VIII deficiency) is a debilitating genetic disorder that is primarily treated with intravenous replacement therapy. Despite a variety of factor VIII protein formulations available, the risk of developing anti-dug antibodies (“inhibitors”) remains. Overall, 20–30% of patients with severe disease develop inhibitors. Current clinical immune tolerance induction protocols to eliminate inhibitors are not effective in all patients, and there are no prophylactic protocols to prevent the immune response. New experimental therapies, such as gene and cell therapies, show promising results in pre-clinical studies in animal models of hemophilia. Examples include hepatic gene transfer with viral vectors, genetically engineered regulatory T cells (Treg), in vivo Treg induction using immune modulatory drugs, and maternal antigen transfer. Furthermore, an oral tolerance protocol is being developed based on transgenic lettuce plants, which suppressed inhibitor formation in hemophilic mice and dogs. Hopefully, some of these innovative approaches will reduce the risk of and/or more effectively eliminate inhibitor formation in future treatment of hemophilia A. PMID:29225598

  8. A new recombinant factor VIII: from genetics to clinical use

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    Santagostino E


    Full Text Available Elena Santagostino Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milan, Italy Abstract: Advances in recombinant technology and knowledge about coagulation factor VIII (FVIII are building a platform for new therapeutic options in patients with hemophilia A. The development of turoctocog alfa, a novel, high-purity, third-generation, B-domain truncated recombinant FVIII, has been produced and formulated without the use of animal-derived or human serum-derived components, in the wake of understanding of the new biochemical characteristics of FVIII, namely its protein structure, and glycosylation and sulfating patterns. Culture conditions and a five-step purification process have been developed to optimize the safety of turoctocog alfa. The results of two pilot clinical trials using turoctocog alfa confirmed high safety levels, with no patient developing inhibitors during the period of observation. The purpose of this review is to describe briefly the molecular and biological properties of turoctocog alfa, together with details of its clinical development, with emphasis on the needs of patients with hemophilia A. Keywords: hemophilia A, recombinant factor VIII, turoctocog alfa, purification, inhibitor, safety


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    Ichsan Luqmana Indra Putra


    Full Text Available Diversity of parasitic Hymenoptera in PTPN VIII oil palm plantation Cindali, Bogor. One group of important natural enemies in oil palm plantation is parasitic Hymenoptera. The purpose of this research is to know the diversity and fluctuation of parasitic Hymenoptera PTPN VIII Cindali oil palm plantation. This research was conducted in 6 blocks of oil palm in September 2014 – June 2015. There were 5 plots in every observation blocks 39.2 x 39.2 m in size, and used direct and indirect method. Direct method done by 5 plants in every plots was taken randomized to observed and taken the herbivore insects to reared until the parasitic Hymenoptera came out. Observation of cover crops conducted by 3 subplots determined diagonally in every plots 9.8 x 9.8 m in size and herbivore insects was observed and collected. Indirect methods used sweep net and yellow pan trap. The result of this research, 26 parasitic Hymenoptera families was found, with the Braconidae was the most morphospecies found and the most individual amount was Scelionidae. The abundance of parasitoid in every month fluctuated.


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    sudyastuti sudyastuti


    Full Text Available This research was conducted based on the phenomenon that happens to grade VIII SMPIT Bina Amal Semarang which has the social conformity low. The purpose of this research is to proof  the influence of counseling service groups towards the conformity. The type of this research is experimental research. The research was conducted with seven times the grant of preferential treatment on grade VIII SMPIT Bina Amal Semarang, research subject with 8 students. The data collection method used is the psychology scale. Data analysis techniques using deskriptif analysis of percentage and wilcoxon test. The results showed incoming students conformity category is middle (59,75%. After being given the treatment through the counseling of the group, a significant unchanged in conformity of students. Conformity of the students in a middle category (60,37%. It shows that conformity of student can’t be influenced through the counseling service groups. Conformity of students not depend on one cause but the another thing to establish it as cohesion,the pretension to change, and the environmental support.


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    Nurul Hidayati Arifani


    Full Text Available This study aims to describe the students' thinking process in solving TIMSS math problem on measurement of angle in geometric shapes based on Polya’s problem solving step associated with Swartz’s thinking process theory. The subject of the research was a grade VIII student in SMP Negeri 4 Malang who was classified as intelligent but made many mistakes when completing the test. Data collection methods used were test and interview methods. The results show that students go through the step of generating ideas, clarifying ideas, assessing the reasonableness of ideas, and thinking complex on every step of problem solving, but at the look back step, students do not clarify the idea. Penelitian ini bertujuan untuk mendeskripsikan proses berpikir siswa dalam menyelesaikan soal matematika TIMSS materi besar sudut dalam bentuk geometris berdasarkan langkah penyelesaian masalah Polya yang dikaitkan dengan teori proses berpikir Swartz. Subjek penelitian adalah seorang siswa kelas VIII di SMP Negeri 4 Malang yang tergolong pandai, tetapi banyak melakukan kesalahan saat menyelesaikan soal tes. Metode pengumpulan data yang digunakan adalah metode tes dan wawancara. Hasil penelitian menunjukkan bahwa siswa dalam menyelesaikan soal TIMSS melalui tahap menghasilkan ide, mengklarifikasi ide, menilai kelayakan ide, dan berpikir kompleks pada setiap langkah penyelesaian masalah. Namun, pada tahap memeriksa kembali, siswa tidak melakukan pengklarifikasian ide.

  12. Characterization of Amm VIII from Androctonus mauretanicus mauretanicus: a new scorpion toxin that discriminates between neuronal and skeletal sodium channels. (United States)

    Alami, Meriem; Vacher, Hélène; Bosmans, Frank; Devaux, Christiane; Rosso, Jean-Pierre; Bougis, Pierre E; Tytgat, Jan; Darbon, Hervé; Martin-Eauclaire, Marie-France


    The venom of the scorpion Androctonus mauretanicus mauretanicus was screened by use of a specific serum directed against AaH II, the scorpion alpha-toxin of reference, with the aim of identifying new analogues. This led to the isolation of Amm VIII (7382.57 Da), which gave a highly positive response in ELISA, but was totally devoid of toxicity when injected subcutaneously into mice. In voltage-clamp experiments with rat brain type II Na+ channel rNa(v)1.2 or rat skeletal muscle Na+ channel rNa(v)1.4, expressed in Xenopus oocytes, the EC50 values of the toxin-induced slowing of inactivation were: 29+/-5 and 416+/-14 nM respectively for AmmVIII and 2.6+/-0.3 nM and 2.2+/-0.2 nM, respectively, for AaH II interactions. Accordingly, Amm VIII clearly discriminates neuronal versus muscular Na+ channel. The Amm VIII cDNA was amplified from a venom gland cDNA library and its oligonucleotide sequence determined. It shows 87% sequence homology with AaH II, but carries an unusual extension at its C-terminal end, consisting of an additional Asp due to a point mutation in the cDNA penultimate codon. We hypothesized that this extra amino acid residue could induce steric hindrance and dramatically reduce recognition of the target by Amm VIII. We constructed a model of Amm VIII based on the X-ray structure of AaH II to clarify this point. Molecular modelling showed that this C-terminal extension does not lead to an overall conformational change in Amm VIII, but drastically modifies the charge repartition and, consequently, the electrostatic dipole moment of the molecule. At last, liquid-phase radioimmunassays with poly- and monoclonal anti-(AaH II) antibodies showed the loss of conformational epitopes between AaH II and Amm VIII.

  13. Evaluation of B&W UO2/ThO2 VIII experimental core: criticality and thermal disadvantage factor analysis

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    Carlo Parisi; Emanuele Negrenti


    In the framework of the OECD/NEA International Reactor Physics Experiment (IRPHE) Project, an evaluation of core VIII of the Babcock & Wilcox (B&W) Spectral Shift Control Reactor (SSCR) critical experiment program was performed. The SSCR concept, moderated and cooled by a variable mixture of heavy and light water, envisaged changing of the thermal neutron spectrum during the operation to encourage breeding and to sustain the core criticality. Core VIII contained 2188 fuel rods with 93% enriched UO2-ThO2 fuel in a moderator mixture of heavy and light water. The criticality experiment and measurements of the thermal disadvantage factor were evaluated.


    Meng, Fantao; Tsai, Amy G.; Intaglietta, Marcos; Acharya, Seetharama A.


    PEGylation of intramolecularly crosslinked Hb has been studied here to overcome the limitation of dissociation of Hb tetramers. New hexa and deca PEGylated low oxygen affi nity PEG-αα-Hbs have been generated. Infl uence of PEG conjugation chemistry and the PEG shell structure on the functional properties as well as PEGylation induced plasma expander like properties of the protein has been delineated. The results have established that in the design of PEG-Hbs as oxygen therapeutics, the infl uence of conjugation chemistry and the PEG shell structure on the oxygen affi nity of Hb needs to be optimized independently besides optimizing the PEG shell structure for inducing resuscitation fluid like properties. PMID:24597567


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    Lisa Sudaryanto


    Full Text Available Central obesity was accumulation of fat in the abdominal region. Many studies showed correlations between central obesity and cardiovascular diseases, e.g. diabetes and dyslipidemia.  This study was conducted to know the difference between HbA1c and lipid profil between the women with and without central obesity. This study was an analytic observational study with cross-sectional design. Subjects of 52 respondents were healthy adult women staff in campus I, II, III Sanata Dharma University in Yogyakarta and selected using purposive sampling technique. The data of waist circumference, pelvic/hip circumference, HbA1c and lipid profile were collected among the subjects and analyzed with computer with 95% confidence interval. The results of this study showed HbA1c levels and lipid profile were different between the women with and without central obesity, although the difference was not statistically significant.

  16. Simulation and Experimental Verification of a HB-Type Vernier Motor

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    R. H. Thejel


    Full Text Available Direct drive motors are used as actuators in numerous applications in which they must rotate at low speeds with high torque and low torque ripple. Various types of vernier motors have been studied recently. The HB type vernier motor is one of them. Its rotor structure is the same as in a HB type stepping motor but has a field winding at the rotor and has multiphase windings in the stator. In the present work, a Matlab simulation of a HB type vernier motor is presented. To validate the motor results and response, the authors fabricated the motor and implemented its drive circuit. The motor was tested for different load conditions. Experimental results are found identical to simulation results and it is also shown that the motor has low torque ripple.

  17. Hb Matera (HBB: c.167 T > A): A Second Case Detected in a Pregnant Chinese Woman by the Capillary Electrophoresis Method. (United States)

    Li, You-qiong; Ye, Li-Hua; Mo, Yun


    Hb Matera (HBB: c.167 T > A) is an unstable β-globin gene variant with an ATG > AAG substitution at codon 55. Its coelution with Hb A2 on high performance liquid chromatography (HPLC) makes it difficult to discriminate between Hb Matera and Hb E (HBB: c.79 G > A) that also coelutes with Hb A2 in this method. However, we found that capillary electrophoresis (CE) was able to detect Hb Matera and discriminate it from Hb E, based on the quantification of the peaks and on hematological parameters.

  18. Anaesthesia in a patient with subarachanoidal haemorrhage and high oxygen affinity haemoglobinopathy (HB york: case report

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    Monaca Enrico


    Full Text Available Abstract Background Approximately 90 haemoglobinopathies have been identified that result in abnormally high oxygen affinity. One of these is haemoglobinopathy York (HbY, first described in 1976. HbY causes an extreme leftward shift of the oxygen dissociation curve with the P50 value changing to 12.5 - 15.5 mmHg (normal value 26.7 mmHg, indicating that approximately half of the haemoglobin is not available as oxygen carrier. Patients with haemoglobinopathies with increased oxygen affinity could suffer from the risk developing ischaemic complications due to a lack of functional oxygen carriers. This is, to best of our knowledge, the first case report on a patient with HbY published in connection with anesthesia. Case Presentation A 42-year-old female with a severe headache and Glasgow coma scale (GCS of 15 was admitted to the neurosurgical intensive care unit with a ruptured, right sided ICA aneurysm with consecutive subarachnoid haemorrhage [Fisher III, World Federation of Neurosurgical Societies (WFNS I]. The medical history of the patient included an erythrocytosis (Hb 17.5 g/dl on the base of a high-oxygen-affinity haemoglobinopathy, called Hb York (HbY. With no time available to take special preoperative precautions, rapid blood loss occurred during the first attempt to clip the aneurysm. General transfusion procedures, according to the guidelines based on haemoglobin and haematocrit values, could not be applied due to the uncertainty in the oxygen carrier reduction. To maintain tissue oxygen supply, clinical indicators of ischaemia were instead utilized to gauge the appropriate required blood products, crystalloids and colloids replacements. Despite this, the patient survived the neurosurgical intervention without any neurological deficit. Conclusions Family members of patients with HbY (and other haemoglobinopathies with increased oxygen affinity should undergo clinical assessment, particularly if they are polycythaemic. If the diagnosis

  19. Determinanti genetici dell’espressione dell’emoglobina HbF


    Manunza, Laura


    Background: Increased levels of fetal hemoglobin (HbF, α2γ2) may reduce beta thalassemia severity. We have investigated the influence of three known major loci on the HbF trait (HBG2, rs7482144; BCL11A, rs1427407; HBS1L-MYB, rs9399137), prevalent Sardinian mutations in human Kruppel-like factor 1 (KLF1) recently reported to be responsible for persistence of high levels of fetal hemoglobin (HPFH) and two new predicted polymorphisms (HBE1 rs67385638; HBG2 rs2855122) involved in t...

  20. Novel interactions of two α-Hb variants with SEA deletion α(0)-thalassemia: hematological and molecular analyses. (United States)

    Srivorakun, Hataichanok; Singha, Kritsada; Fucharoen, Goonnapa; Fucharoen, Supan


    To report the hematological and molecular features as well as diagnostic aspects of the hitherto un-described interactions of two rare α-globin chain variants with α(0)-thalassemia commonly found among Southeast Asian populations. The study was done on two adult Thai patients (P1 and P2) who had hypochromic microcytic anemia. Hb analysis was carried out using high performance liquid chromatography (HPLC) and capillary electrophoresis (CE). Mutations were identified by PCR and related techniques. Hb analysis of P1 using HPLC showed a normal Hb pattern, but CE demonstrated an abnormal peak at zone 7. DNA sequencing identified a CCG-CTG mutation at codon 95 of the α2 globin gene corresponding to the Hb G-Georgia [α95(G2)Pro → Leu(α2)] previously undescribed in the Thai population. In contrast, Hb analysis of P2 demonstrated an abnormal peak not fully separated from Hb A on HPLC, but not on CE. DNA analysis identified the rarely described Hb Nakhon Ratchasima [α63(E12)Ala → Val(α2)] mutation. Routine DNA analysis detected the SEA deletion α(0)-thalassemia in trans to the Hb variants in both cases. Hematological parameters were compared with those of patients with compound heterozygote for other α-globin variants and α(0)-thalassemia previously documented. Identification of the patients confirmed that interaction of these rare Hb variants with α(0)-thalassemia does not lead to the Hb H disease. Differentiation of these two Hb variants from other clinically relevant hemoglobinopathies in a routine setting is, however, necessary. This can be accomplished using a combined Hb-HPLC and CE analysis followed by PCR-RFLP assays.

  1. The scorpion toxin Amm VIII induces pain hypersensitivity through gain-of-function of TTX-sensitive Na⁺ channels. (United States)

    Abbas, Najwa; Gaudioso-Tyzra, Christelle; Bonnet, Caroline; Gabriac, Mélanie; Amsalem, Muriel; Lonigro, Aurélie; Padilla, Françoise; Crest, Marcel; Martin-Eauclaire, Marie-France; Delmas, Patrick


    Voltage-gated Na(+) channels (Nav) are the targets of a variety of scorpion toxins. Here, we investigated the effects of Amm VIII, a toxin isolated from the venom of the scorpion Androctonus mauretanicus mauretanicus, on pain-related behaviours in mice. The effects of Amm VIII were compared with the classic scorpion α-toxin AaH II from Androctonus australis. Contrary to AaH II, intraplantar injection of Amm VIII at relatively high concentrations caused little nocifensive behaviours. However, Amm VIII induced rapid mechanical and thermal pain hypersensitivities. We evaluated the toxins' effects on Nav currents in nociceptive dorsal root ganglion (DRG) neurons and immortalized DRG neuron-derived F11 cells. Amm VIII and AaH II enhanced tetrodotoxin-sensitive (TTX-S) Nav currents in DRG and F11 cells. Both toxins impaired fast inactivation and negatively shifted activation. AaH II was more potent than Amm VIII at modulating TTX-S Nav currents with EC50 of 5 nM and 1 μM, respectively. AaH II and Amm VIII also impaired fast inactivation of Nav1.7, with EC50 of 6.8 nM and 1.76 μM, respectively. Neither Nav1.8 nor Nav1.9 was affected by the toxins. AaH II and Amm VIII reduced first spike latency and lowered action potential threshold. Amm VIII was less efficient than AaH II in increasing the gain of the firing frequency-stimulation relationship. In conclusion, our data show that Amm VIII, although less potent than AaH II, acts as a gating-modifier peptide reminiscent of classic α-toxins, and suggest that its hyperalgesic effects can be ascribed to gain-of-function of TTX-S Na(+) channels in nociceptors. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  2. Epitope mapping of inhibitory antibodies targeting the C2 domain of coagulation factor VIII by hydrogen-deuterium exchange mass spectrometry (United States)

    Sevy, Alexander M.; Healey, John F.; Deng, Wei; Spiegel, P. Clint; Meeks, Shannon L.; Li, Renhao


    Summary Background The development of anti-factor VIII (fVIII) antibodies (inhibitors) is a significant complication in the management of patients with hemophilia A, leading to significant increases in morbidity and treatment cost. Using a panel of anti-fVIII monoclonal antibodies (MAbs) to different epitopes on fVIII, we recently have shown that epitope specificity, inhibitor kinetics, and time to maximum inhibition are more important than inhibitor titer in predicting response to fVIII and the combination of fVIII and recombinant factor VIIa. In particular, a subset of high-titer inhibitors responded to high dose fVIII, which would not be predicted based on their inhibitor titer alone. Thus the ability to quickly map the epitope spectrum of patient plasma using a clinically feasible assay may fundamentally change how clinicians approach the treatment of high-titer inhibitor patients. Objectives To map the epitopes of anti-fVIII MAbs, of which 3 are classical inhibitors and one non-classical, using hydrogen-deuterium exchange coupled with liquid chromatography-mass spectrometry (HDX-MS). Methods Binding epitopes of 4 MAbs targeting fVIII C2 domain were mapped using HDX-MS. Results The epitopes determined by HDX-MS are consistent with those obtained earlier through structural characterization and antibody competition assays. In addition classical and non-classical inhibitor epitopes could be distinguished using a limited subset of C2-derived peptic fragments. Conclusion Our results demonstrate the effectiveness and robustness of the HDX-MS method for epitope mapping and suggest a potential role of rapid mapping of fVIII inhibitor epitopes in facilitating individualized treatment of inhibitor patients. PMID:24152306

  3. Further studies on Hb Canebière [β12(G4)Asn→His], a low affinity hemoglobin variant

    DEFF Research Database (Denmark)

    Froelund, Ulf; Sandbakken, Erik; Szecsi, Pal Bela


    A case of Hb Canebière [ß102(G4)Asn¿His] was diagnosed in an otherwise healthy 21-year-old Danish woman. The clinical consequences were minor, since her only symptom consisted of transient cyanosis in lips and fingers when exposed to cold environments. Whole blood p50 was 59.9 mmHg. The Hb Canebi...... Canebière variant could not be separated from Hb A by high performance liquid chromatography (HPLC) and isoelectric focusing (IEF), and it was thus missed by routine hemoglobin (Hb) fractionation techniques....

  4. Study of the effects of polymerized porcine hemoglobin (pPolyHb) in an acute anemia rat model. (United States)

    Liu, Huifang; Yan, Chengbin; Yan, Kunping; Zhu, Wenjin; Shen, Yuesheng; Yang, Bo; Chen, Chao; Zhu, Hongli


    The objective of this study was to investigate the recovery ability of polymerized porcine hemoglobin (pPolyHb) in a rat model of acute anemia caused by normovolemic hemodilution (ANH). After the ANH procedure, rats were infused with either pPolyHb or red blood cells. The results showed pPolyHb could carry a sufficient amount of oxygen to the tissues to maintain normal aerobic metabolism and hemodynamic stability, without any significant toxic effects on renal and liver function according to pathological, and biochemical analysis. The data suggest pPolyHb may be a good candidate for the treatment of acute anemia in future clinical trials.

  5. Further studies on Hb Canebière [β12(G4)Asn→His], a low affinity hemoglobin variant

    DEFF Research Database (Denmark)

    Froelund, Ulf; Sandbakken, Erik; Szecsi, Pal Bela


    A case of Hb Canebière [β102(G4)Asn→His] was diagnosed in an otherwise healthy 21-year-old Danish woman. The clinical consequences were minor, since her only symptom consisted of transient cyanosis in lips and fingers when exposed to cold environments. Whole blood p50 was 59.9 mmHg. The Hb Canebi...... Canebière variant could not be separated from Hb A by high performance liquid chromatography (HPLC) and isoelectric focusing (IEF), and it was thus missed by routine hemoglobin (Hb) fractionation techniques....

  6. Antibacterial activity of a modified unfilled resin containing a novel polymerizable quaternary ammonium salt MAE-HB. (United States)

    Huang, Li; Yu, Fan; Sun, Xiang; Dong, Yan; Lin, Ping-Ting; Yu, Hao-Han; Xiao, Yu-Hong; Chai, Zhi-Guo; Xing, Xiao-Dong; Chen, Ji-Hua


    Resins with strong and long-lasting antibacterial properties are critical for the prevention of secondary dental caries. In this study, we evaluated the antibacterial effect and the underlying mechanism of action of an unfilled resin incorporating 2-methacryloxylethyl hexadecyl methyl ammonium bromide (MAE-HB) against Streptococcus mutans UA159 (S. mutans UA159). MAE-HB was added into unfilled resin at 10 mass%, and unfilled resin without MAE-HB served as the control. Bacterial growth was inhibited on 10%-MAE-HB unfilled resin compared with the control at 1 d, 7 d, 30 d, or 180 d (P  0.05). No significant differences in the antibacterial activities of eluents from control versus 10%-MAE-HB unfilled resins were observed at any time point (P > 0.05). The number of bacteria attached to 10%-MAE-HB unfilled resin was considerably lower than that to control. Fe-SEM and CLSM showed that 10%-MAE-HB unfilled resin disturbed the integrity of bacterial cells. Expression of the bacterial glucosyltransferases, gtfB and gtfC, was lower on 10%-MAE-HB unfilled resin compared to that on control (P HB confers unfilled resin with strong and long-lasting antibacterial effects against S. mutans.

  7. Fetal Anemia and Hydrops Fetalis Associated with Homozygous Hb Constant Spring (HBA2: c.427T > C). (United States)

    He, Yi; Zhao, Ying; Lou, Ji-Wu; Liu, Yan-Hui; Li, Dong-Zhi


    Hb Constant Spring (Hb CS, HBA2: c.427T > C) is a common nondeletional α-thalassemia (α-thal) that results from a nucleotide substitution at the termination codon of the α2-globin gene. Homozygosity for Hb CS (α(CS)α/α(CS)α) is relatively rare, and generally characterized with mild hemolytic anemia, jaundice, and splenomegaly. In this report we present a fetus with cardiomegaly, pericardial effusion, enlarged placenta and increased middle cerebral artery-peak systolic velocity (MCA-PSV) at 24 weeks' gestation. Fetal blood sampling revealed the severe anemia [hemoglobin (Hb) level being 4.8 g/dL] and Hb H (β4) disease-like hematological findings with Hb Bart's (γ4) level of 17.9%. DNA sequencing of the α-globin genes found that both partners were Hb CS carriers and the fetus was an Hb CS homozygote. Therefore, this was a rare case of homozygous Hb CS which demonstrated an unusual and serious anemia and hydrops fetalis in utero.

  8. Hb A1c Determination by Capillary Electrophoresis is an Efficient Method for Detecting β-Thalassemias and Hemoglobin Variants. (United States)

    Orts, Juan A; Zúñiga, Ángel; Bello, Yanis; Fabregat, Aleix B; Vicente, Ana I


    Glycated hemoglobin (Hb A1c) determination by multicapillary zone electrophoresis (MZE) can additionally be used to detect Hb A2, Hb F and most common hemoglobin (Hb) variants. We assessed the effectiveness of this method for detecting β-thalassemia (β-thal), δβ-thalassemia (δβ-thal) and most common Hb variants. Moreover, Hb F/Hb A2 is evaluated as an index for discriminating between β- and δβ-thal traits. The theoretical β-thalassemia major (β-TM) birth rate in our healthcare area is calculated and contrasted with real data. A MZE technique was used for Hb A1c measurements in 27,724 patients. Previous criteria for carrier detection were established and subsequently confirmed by molecular biology techniques. Positive predictive value (PPV) was 100.0%. The prevalence of β-thal trait (including δβ-thal) was 0.34%. The most prevalent mutations (estimated per 100,000 population) were HBB: c.118C > T (57.7%), HBB: c.93-21G>A (50.5%), HBB: c.92 + 1G > A (43.3%), HBB: c.92 + 6T > C (32.5%) and HBB: c.20delA (18.0%) for β-thalassemias, and Hb S (HBB: c.20A > T) (32.5%) and Hb J-Baltimore (HBB:c.3880T>A) (28.9%) for Hb variants. We found a paradoxical result between the theoretical β-TM birth rate and real data. We calculated an optimal Hb F/Hb A2 index cutoff of 0.71 for discriminating between β- and δβ-thal traits. This method is highly cost-effective for detecting β-thalassemias and common Hb variants. Prevalence results match previous data for the Spanish population. Heterogeneity of mutations in Spain has markedly increased as a consequence of migration. The Hb F/Hb A2 index cutoff could be used to predict δβ-thal trait.

  9. Analysis of the rs35959442 polymorphism in Hb E/β-thalassemia in Guangxi Province of the Republic of China. (United States)

    He, Yunyan; Chen, Ping; Lin, Weixiong; Luo, Jianming


    Hb E [β26(B8)Glu→Lys]/β-thalassemia (β-thal) is a worldwide inherited disorder. We determined the phenotype of 65 unrelated Hb E/β-thal subjects and 70 healthy individuals in the Guangxi Province of the Republic of China (ROC). Single nucleotide polymorphism (SNP) rs35959442 in HBS1L analysis was performed using the polymerase chain reaction (PCR)/restriction enzyme method. The data suggested that the frequency of the rs35959442 polymorphism was relatively high in patients with Hb E/β-thal in Guangxi Province, ROC, when associated with Hb F augmentation.

  10. Posterior transverse interarch discrepancy on HbE β thalassemia patients

    Directory of Open Access Journals (Sweden)

    Yuniar Zen


    Full Text Available Background: One of the symptoms that often arises on thalassemia patients is disharmony dentofacial, class II skeletal malocclusion, as a result of the malrelation of maxilla and mandible. This malrelation can be affected by either maxillary bone position, dentoalveolar maxillary position, mandibular bone position, dentoalveolar mandibular position, or combinations of those components. Purpose: The study was aimed to examine whether there is posterior transverse interarch discrepancy on the HbE β thalassemia patients or not. Methods: This study is an observational research with cross-sectional design. The sample consisted of 33 HbE β thalassemia patients and 33 non-thalassemia patients as a control group aged 12–14 years. Lateral cephalogram was carried out and dental casts of maxillary and mandibular dental arches were also taken in all of those patients. Results: There was no difference between the maxillary intermolar width of the HbE β thalassemia patients and that of the normal ones, but the mandibular intermolar width of the HbE β thalassemia patients was significantly smaller than that of the normal ones. Beside that, posterior transverse interarch discrepancy of of the HbE β thalassemia patients was significantly greater than that of the normal ones, which showed great difference between maxillary and mandibular intermolar widths. Conclusion: Posterior transverse interarch discrepancy of the HbE β thalassemia patients was different from that of the normal ones. The dentofacial abnormalities on the HbE β thalassemia patients aged 12–14 years primarily was due to disporposional dentofacial growth in the vertical, sagittal, and transversal directions, especially in the posterior region.Latar belakang: Salah satu akibat yang sering timbul pada penderita talasemia adalah disharmoni dentofasial berupa maloklusi skeletal kelas II yang merupakan kelainan hubungan maksila dan mandibula. Malrelasi ini dapat dipengaruhi oleh posisi

  11. Keefektifan Experiential Learning Berbantuan Origami Terhadap Kemampuan Keruangan Siswa Kelas VIII

    Directory of Open Access Journals (Sweden)

    Isnaeni Umi Machromah


    Full Text Available AbstrakPenelitian eksperimen ini bertujuan untuk mengetahui keefektifan pembelajaran Experiential Learning berbantuan origami terhadap kemampuan keruangan siswa dengan kualifikasi keefektifan yang telah ditentukan. Populasi yaitu siswa kelas VIII SMP Negeri 3 Colomadu tahun pelajaran 2012/2013. Sampel diambil secara simple random sampling. Hasil penelitian ini yaitu: (1 Uji proporsi ketuntasan belajar menunjukkan siswa kelompok eksperimen telah mencapai ketuntasan belajar; (2 Uji perbedaan dua rata-rata menghasilkan simpulan bahwa rata-rata hasil post-test kemam-puan keruangan siswa kelompok eksperimen lebih dari kelompok kontrol; (3 Analisis re-gresi menunjukkan bahwa motivasi belajar siswa memberikan pengaruh positif sebesar 49,3% terhadap kemampuan keruangan siswa; (4 Uji gain ternormalisasi menunjukkan terdapat peningkatan kemampuan keruangan siswa secara signifikan pada kategaori sedang untuk kelompok eksperimen dan kategori rendah untuk kelompok kontrol. Simpulan yang diperoleh yaitu Experiential Learning berbantuan origami efektif terhadap kemampuan keruangan siswa kelas VIII. AbstractThis experiment research aims to determine the effectiveness of Experiential Learning with Origami to the students’s spatial abilities by the criteria of effectiveness. The population of this research is students of grade VIII of SMP Negeri 3 Colomadu 2012/2013 academic year. Independent variables used in this research are learning by Experiential Learning with origami and student’s motivation. While the dependent variable is the student’s spatial abilities. This research is using documentation, spatial abilities’s test, dan motivation’s scale for collecting data method. Result of this research are: (1 proportion test show that the experiment group has reached mastering of learning clasically and personally; (2 result of spatial ablities’s post test in experiment group better than control group; (3 result of regretion shows that student

  12. Analysis of factor VIII gene inversions in 164 unrelated hemophilia A families

    Energy Technology Data Exchange (ETDEWEB)

    Vnencak-Jones, L.; Phillips, J.A. III; Janco, R.L. [Vanderbilt Univ. School of Medicine, Nashville, TN (United States)] [and others


    Hemophilia A is an X-linked recessive disease with variable phenotype and both heterogeneous and wide spread mutations in the factor VIII (F8) gene. As a result, diagnostic carrier or prenatal testing often relies upon laborious DNA linkage analysis. Recently, inversion mutations resulting from an intrachromosomal recombination between DNA sequences in one of two A genes {approximately}500 kb upstream from the F8 gene and a homologous A gene in intron 22 of the F8 gene were identified and found in 45% of severe hemophiliacs. We have analyzed banked DNA collected since 1986 from affected males or obligate carrier females representing 164 unrelated hemophilia A families. The disease was sporadic in 37%, familial in 54% and in 10% of families incomplete information was given. A unique deletion was identified in 1/164, a normal pattern was observed in 110/164 (67%), and 53/164 (32%) families had inversion mutations with 43/53 (81%) involving the distal A gene (R3 pattern) and 10/53 (19%) involving the proximal A gene (R2 pattern). While 19% of all rearrangements were R2, in 35 families with severe disease (< 1% VIII:C activity) all 16 rearrangements seen were R3. In 18 families with the R3 pattern and known activities, 16 (89%) had levels < 1%, with the remaining 2 families having {le} 2.4% activity. Further, 18 referrals specifically noted the production of inhibitors and 8/18 (45%) had the R3 pattern. Our findings demonstrate that the R3 inversion mutation patterns is (1) only seen with VIII:C activity levels of {le} 2.4%, (2) seen in 46% of families with severe hemophilia, (3) seen in 45% of hemophiliacs known to have inhibitors, (4) not correlated with sporadic or familial disease and (5) not in disequilibrium with the Bcl I or Taq I intron 18 or ST14 polymorphisms. Finally, in families positive for an inversion mutation, direct testing offers a highly accurate and less expensive alternative to DNA linkage analysis.

  13. Hemophilia A gene therapy via intraosseous delivery of factor VIII-lentiviral vectors. (United States)

    Miao, Carol H


    Current treatment of hemophilia A (HemA) patients with repeated infusions of factor VIII (FVIII; abbreviated as F8 in constructs) is costly, inconvenient, and incompletely effective. In addition, approximately 25 % of treated patients develop anti-factor VIII immune responses. Gene therapy that can achieve long-term phenotypic correction without the complication of anti-factor VIII antibody formation is highly desired. Lentiviral vector (LV)-mediated gene transfer into hematopoietic stem cells (HSCs) results in stable integration of FVIII gene into the host genome, leading to persistent therapeutic effect. However, ex vivo HSC gene therapy requires pre-conditioning which is highly undesirable for hemophilia patients. The recently developed novel methodology of direct intraosseous (IO) delivery of LVs can efficiently transduce bone marrow cells, generating high levels of transgene expression in HSCs. IO delivery of E-F8-LV utilizing a ubiquitous EF1α promoter generated initially therapeutic levels of FVIII, however, robust anti-FVIII antibody responses ensued neutralized functional FVIII activity in the circulation. In contrast, a single IO delivery of G-FVIII-LV utilizing a megakaryocytic-specific GP1bα promoter achieved platelet-specific FVIII expression, leading to persistent, partial correction of HemA in treated animals. Most interestingly, comparable therapeutic benefit with G-F8-LV was obtained in HemA mice with pre-existing anti-FVIII inhibitors. Platelets is an ideal IO delivery vehicle since FVIII stored in α-granules of platelets is protected from high-titer anti-FVIII antibodies; and that even relatively small numbers of activated platelets that locally excrete FVIII may be sufficient to promote efficient clot formation during bleeding. Additionally, combination of pharmacological agents improved transduction of LVs and persistence of transduced cells and transgene expression. Overall, a single IO infusion of G-F8-LV can generate long-term stable

  14. Storage of factor VIII variants with impaired von Willebrand factor binding in Weibel-Palade bodies in endothelial cells

    NARCIS (Netherlands)

    van den Biggelaar, Maartje; Bouwens, Eveline A. M.; Voorberg, Jan; Mertens, Koen


    Point mutations resulting in reduced factor VIII (FVIII) binding to von Willebrand factor (VWF) are an important cause of mild/moderate hemophilia A. Treatment includes desmopressin infusion, which concomitantly increases VWF and FVIII plasma levels, apparently from storage pools containing both

  15. Requirements for cellular co-trafficking of factor VIII and von Willebrand factor to Weibel-Palade bodies

    NARCIS (Netherlands)

    van den Biggelaar, M.; Bierings, R.; Storm, G.; Voorberg, J.; Mertens, K.


    von Willebrand factor (VWF) serves a critical role as a carrier of factor (F)VIII in circulation. While it is generally believed that FVIII and VWF assemble in circulation after secretion from different cells, an alternative view is that cells should exist that co-express FVIII and VWF. In this

  16. Effectiveness of Peer Tutoring in Learning English among Tutors and Tutees of Class VIII Students in Kancheepuram DT (United States)

    Marieswari, M.; Prema, N.


    The peer who teaches to their mates is peer tutoring. It is a common instructional strategy used in classrooms. The aim of this study is to know whether there is any improvement in achievement marks of tutors and tutees after the process of peer tutoring. Class VIII students were selected as the sample for the present experimental study. The…

  17. Evaluation of the biological differences of canine and human factor VIII in gene delivery: Implications in human hemophilia treatment (United States)

    The canine is the most important large animal model for testing novel hemophilia A(HA) treatment. It is often necessary to use canine factor VIII (cFIII) gene or protein for the evaluation of HA treatment in the canine model. However, the different biological properties between cFVIII and human FVII...

  18. Mediastinal, subcutaneous and multiple muscular abscesses caused by group B streptococcus serotype VIII in a type 2 diabetes mellitus patient. (United States)

    Omura, Yuka; Kusama, Yoshiki; Takeuchi, Noriko; Ishiwada, Naruhiko


    We report a case of mediastinal subcutaneous and multiple muscular abscesses caused by group B streptococcus serotype VIII in a type 2 diabetes mellitus patient. The patient arrived at the hospital with the chief complaint of immobility, and blood examination results suggested an acute infection and poorly controlled diabetes mellitus. Group B streptococcal bacteria were cultured from the patient's blood, and identified as serotype VIII upon further analysis. The patient recovered without any sequelae after percutaneous drainage, antibiotic therapy, and intensive glycemic control. Although the incidence of group B streptococcal infection in non-pregnant adults has recently increased in many developed countries, information on serotype VIII infection is quite limited. The reason is that serotype VIII group B streptococci are a Japan-specific serotype, and rarely cause invasive infections, even in Japan. Therefore, further surveillance and case reports should be documented in the future. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  19. Factor VIII genotype and inhibitor development in patients with haemophilia A: highest risk in patients with splice site mutations.

    NARCIS (Netherlands)

    Boekhorst, J.; Lari, G.R.; D'Oiron, R.; Costa, J.M.; Novakova, I.R.O.; Ala, F.A.; Lavergne, J.M.; Heerde, W.L. van


    The appearance of inhibitory antibodies against factor VIII (FVIII) is the most severe and costly complication of replacement therapy in patients with haemophilia A (HA). To determine the relationship between FVIII genotype and inhibitor development, baseline FVIII activity, genotype and inhibitor

  20. 77 FR 42696 - Notice of New Fee Sites; Federal Lands Recreation Enhancement Act, (Title VIII, Pub. L. 108-447) (United States)


    ... Forest Service Notice of New Fee Sites; Federal Lands Recreation Enhancement Act, (Title VIII, Pub. L... Laws, Recreation Fee Coordinator, 406-283-7648 SUPPLEMENTARY INFORMATION: The Federal Recreation Lands... advance notice in the Federal Register whenever new recreation fee areas are established. This new fee...

  1. 78 FR 19445 - Notice of Proposed New Fee Sites; Federal Lands Recreation Enhancement Act, (Title VIII, Pub. L... (United States)


    ... Forest Service Notice of Proposed New Fee Sites; Federal Lands Recreation Enhancement Act, (Title VIII... and maintenance of these recreation sites. Lake Canyon Recreation Area is a fee campground with 54... is to keep the site fees consistent with other campsites in the Lake Canyon Recreation Area. The fee...

  2. 75 FR 2850 - Notice of Proposed New Fee Sites; Federal Lands Recreation Enhancement Act, (Title VIII, Pub. L... (United States)


    ... Forest Service Notice of Proposed New Fee Sites; Federal Lands Recreation Enhancement Act, (Title VIII... and recreation experiences. A financial analysis is being completed to determine fee rates. The.... Recreation Passes such as the Northwest Forest Pass would cover day use fees for this trailhead. Northwest...

  3. 76 FR 36518 - Notice of Meeting; Federal Lands Recreation Enhancement Act (Title VIII, Pub. L. 108-447) (United States)


    .... 2. An increase of fees for the Shelf Road Recreation Area in the Royal Gorge Field Office of the BLM..., Bureau of Land Management staff and Committee members. Persons who wish to bring recreation fee matters... Forest Service Notice of Meeting; Federal Lands Recreation Enhancement Act (Title VIII, Pub. L. 108-447...

  4. 75 FR 21583 - Notice of Proposed New Fee Site; Federal Lands Recreation Enhancement Act (Title VIII, Pub. L... (United States)


    ... Forest Service Notice of Proposed New Fee Site; Federal Lands Recreation Enhancement Act (Title VIII, Pub... improve the recreation experience. An analysis of the campground shows that the proposed fees are..., Moab/Monticello Recreation Fee Coordinator, 435-636-3367. Information about proposed fee changes can...

  5. 78 FR 52499 - Notice of New Fee Site; Federal Lands Recreation Enhancement Act, (Title VIII, Pub. L. 108-447) (United States)


    ... Forest Service Notice of New Fee Site; Federal Lands Recreation Enhancement Act, (Title VIII, Pub. L. 108-447) AGENCY: Monongahela National Forest, Forest Service, USDA. ACTION: Notice of new fee site... new recreation fee areas are established. This new fee will be reviewed by the Eastern Region...

  6. 78 FR 41783 - Notice of Proposed New Fee Sites; Federal Lands Recreation Enhancement Act, (Title VIII, Pub. L... (United States)


    ... Forest Service Notice of Proposed New Fee Sites; Federal Lands Recreation Enhancement Act, (Title VIII... comments can be compiled, analyzed and shared with a Recreation Resource Advisory Committee. New fees would... advance notice in the Federal Register whenever new recreation fee areas are established. Once public...

  7. 75 FR 80789 - Notice of New Fee Site; Federal Lands Recreation Enhancement Act, (Title VIII, Pub. L. 108-447) (United States)


    ... Forest Service Notice of New Fee Site; Federal Lands Recreation Enhancement Act, (Title VIII, Pub. L. 108... Agriculture to publish a six month advance notice in the Federal Register whenever new recreation fee areas are established. This new fee will be reviewed by the Colorado Recreation Resource Advisory Committee...

  8. Chromosome VIII disomy influences the nonsense suppression efficiency and transition metal tolerance of the yeast Saccharomyces cerevisiae. (United States)

    Zadorsky, S P; Sopova, Y V; Andreichuk, D Y; Startsev, V A; Medvedeva, V P; Inge-Vechtomov, S G


    The SUP35 gene of the yeast Saccharomyces cerevisiae encodes the translation termination factor eRF3. Mutations in this gene lead to the suppression of nonsense mutations and a number of other pleiotropic phenotypes, one of which is impaired chromosome segregation during cell division. Similar effects result from replacing the S. cerevisiae SUP35 gene with its orthologues. A number of genetic and epigenetic changes that occur in the sup35 background result in partial compensation for this suppressor effect. In this study we showed that in S. cerevisiae strains in which the SUP35 orthologue from the yeast Pichia methanolica replaces the S. cerevisiae SUP35 gene, chromosome VIII disomy results in decreased efficiency of nonsense suppression. This antisuppressor effect is not associated with decreased stop codon read-through. We identified SBP1, a gene that localizes to chromosome VIII, as a dosage-dependent antisuppressor that strongly contributes to the overall antisuppressor effect of chromosome VIII disomy. Disomy of chromosome VIII also leads to a change in the yeast strains' tolerance of a number of transition metal salts. Copyright © 2015 John Wiley & Sons, Ltd.

  9. 75 FR 5759 - Notice of New Recreation Fee Site; Federal Lands Recreation Enhancement Act, (Title VIII, Pub. L... (United States)


    ... Forest Service Notice of New Recreation Fee Site; Federal Lands Recreation Enhancement Act, (Title VIII... Recreation Fee Sites. SUMMARY: The Soda Springs Ranger District of the Caribou-Targhee National Forest is... appreciate and enjoy the availability of developed recreation campground and picnicking facilities. This...

  10. 75 FR 4340 - Notice of New Recreation Fee Site; Federal Lands Recreation Enhancement Act, (Title VIII, Pub. L... (United States)


    ... Forest Service Notice of New Recreation Fee Site; Federal Lands Recreation Enhancement Act, (Title VIII.... SUPPLEMENTARY INFORMATION: The Federal Recreation Lands Enhancement Act (Title VII, Pub. L. 108-447) directed... new recreation fee areas are established. The Caribou-Targhee National Forest currently has nine other...

  11. 75 FR 26711 - Notice of New Recreation Fee Site; Federal Lands Recreation Enhancement Act, (Title VIII, Pub. L... (United States)


    ... No: 2010-11040] DEPARTMENT OF AGRICULTURE Forest Service Notice of New Recreation Fee Site; Federal Lands Recreation Enhancement Act, (Title VIII, Pub. L. 108-447) AGENCY: National Forests in Mississippi, USDA Forest Service. ACTION: Notice of New Recreation Fee Site. SUMMARY: Bethel Motorcycle and Bethel...

  12. 75 FR 26714 - Notice of Proposed New Recreation Fee Site; Federal Lands Recreation Enhancement Act, (Title VIII... (United States)


    ... No: 2010-11042] DEPARTMENT OF AGRICULTURE Forest Service Notice of Proposed New Recreation Fee Site; Federal Lands Recreation Enhancement Act, (Title VIII, Pub. L. 108-447) AGENCY: National Forests in Mississippi, USDA Forest Service. ACTION: Notice of Proposed New Recreation Fee Site. SUMMARY: Rattlesnake Bay...

  13. Predictors of HbA1c levels in patients initiating metformin

    NARCIS (Netherlands)

    Martono, Doti P; Hak, Eelko; Lambers Heerspink, Hiddo; Wilffert, Bob; Denig, Petra


    Objective: The aim was to assess demographic and clinical factors as predictors of short (6 months) and long term (18 months) HbA1c levels in diabetes patients initiating metformin treatment. Research design and methods: We conducted a cohort study including type 2 diabetes patients who received

  14. Relationship between HbA1C and 2-hour post glucose load as a ...

    African Journals Online (AJOL)

    Objective- To evaluate the performance of HbA1c as a screening tool for type 2 diabetes among Nigerians with systemic hypertension. Design- Cross-sectional. Setting- Hospital based study. Subjects-Two-hundred and seven subjects were recruited, out of which 131had oral glucose tolerance test done. 2-hour post ...

  15. Association between blood group and susceptibility to malaria and its effects on platelets, TLC, and Hb. (United States)

    Burhan, Hira; Hasan, Askari Syed; Mansur-Ul-Haque, Syed; Zaidi, Ghazanfar; Shaikh, Taha; Zia, Aisha


    According to the World Health Organization, the estimated number of malaria cases in Pakistan is about 1.5 million. Hematological variables like platelets, total leukocyte count (TLC), and hemoglobin (Hb) need to be evaluated to diagnose malaria in suspects. This study aimed to investigate the association between blood group and susceptibility to malaria and effects on platelets, TLC, and Hb. This was a case-control study with a sample size of 446, of which 224 were malarial cases and 222 were controls. A designated questionnaire was developed to know age, gender, malarial strain, Hb, TLC, platelets, and blood group. Of 224 malarial cases, 213 were P. vivax, and 11 were P. falciparum. There were 58 patients with blood group A, 72 with group B, 69 were O and 23 were AB. There was no significant difference in the blood group of controls compared to malarial patients (p > 0.05). Mean Hb level was 11.5mg/dL in malaria patients and 12.5mg/dL in controls. There was significant difference (pTLC was not significant between malarial and control groups (p = 0.072). Males were two times susceptible to malaria. There was no significant association between the type of blood group and susceptibility to malaria or developing anemia or thrombocytopenia.

  16. Correlation of MMP-9, GA, HbA1c, and adipokines levels with DR

    Directory of Open Access Journals (Sweden)

    Cheng Qian


    Full Text Available AIM: To investigate the correlation of matrix metalloproteinase -9(MMP-9, glycated albumin(GA, glycosylated hemoglobin(HbA1cand adipokines(including visfatin, resistin and leptinwith diabetic retinopathy(DR. METHODS: From March 2015 to March 2017, 74 patients with DR were treated in our hospital, including 40 patients(80 eyeswith non proliferative diabetic retinopathy(NPDRand 34 patients(68 eyeswith proliferative diabetic retinopathy(PDR, and diabetes mellitus 40 patients(80 eyeswith non DR(NDRand 40 healthy volunteers(80 eyeswere selected as controls, the levels of MMP-9, GA, HbA1c, visfatin, resistin and leptin in each group were detected. RESULTS: PDR group visfatin was 4.41±0.82ng/mL, was significantly lower than the NPDR group, NDR group and control group(PPPPrs=0.523, 0.461 and 0.414, Prs=-0.433, Prs=0.401 and 0.460, PCONCLUSION: MMP-9, GA, HbA1c, and adipokines may play a role in the development and progression of DR, in which MMP-9 is associated with adipokines, both are not significantly related to the levels of GA and HbA1c.

  17. LSST camera grid structure made out of ceramic composite material, HB-Cesic (United States)

    Kroedel, Matthias R.; Langton, J. Bryan


    In this paper we are presenting the ceramic design and the fabrication of the camera structure which is using the unique manufacturing features of the HB-Cesic technology and associated with a dedicated metrology device in order to ensure the challenging flatness requirement of 4 micron over the full array.

  18. Isolation and characterization of atrazine mineralizing Bacillus subtilis strain HB-6.

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    Jinhua Wang

    Full Text Available Atrazine is a widely used herbicide with great environmental concern due to its high potential to contaminate soil and waters. An atrazine-degrading bacterial strain HB-6 was isolated from industrial wastewater and the 16S rRNA gene sequencing identified HB-6 as a Bacillus subtilis. PCR assays indicated that HB-6 contained atrazine-degrading genes trzN, atzB and atzC. The strain HB-6 was capable of utilizing atrazine and cyanuric acid as a sole nitrogen source for growth and even cleaved the s-triazine ring and mineralized atrazine. The strain demonstrated a very high efficiency of atrazine biodegradation with a broad optimum pH and temperature ranges and could be enhanced by cooperating with other bacteria, suggesting its huge potential for remediation of atrazine-contaminated sites. To our knowledge, there are few Bacillus subtilis strains reported that can mineralize atrazine, therefore, the present work might provide some new insights on atrazine remediation.

  19. HbA2 measurements in β-thalassemia and in other conditions

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    Giovanni Ivaldi


    Full Text Available Quite a few papers have been written on the significance of elevated hemoglobin (Hb A2 as a parameter for the diagnosis of β-thalassemia trait, on the cutoff values to be used in diagnostics and on the significance and effects of factors reducing or elevating the expression of HbA2 and last but not least on the need for reliable measurement methods and precise calibrations with accurate standards. However, little has been published on the causes that elevate or reduce the HbA2 levels in β- and a-thalassemia and in other conditions. For a better understanding of the value of a precise measurement of this parameter we summarize and elucidate in this review the direct and indirect mechanisms that cause the variations in HbA2 expression and that influence the value of this parameter in particular conditions. We conclude by explaining the advantages and disadvantages of trusting on a precise measurement in the complete diagnostic contest.

  20. Prevention and control of Hb Bart's disease in Guangxi Zhuang Autonomous Region, China. (United States)

    He, Sheng; Zhang, Qiang; Li, Dongming; Chen, Shaoke; Tang, Yanqing; Chen, Qiuli; Zheng, Chenguang


    To demonstrate the performance of Hb Bart's Disease prevention in Guangxi Zhuang Autonomous Region, China. A prenatal control program for Hb Bart's disease was conducted from January 2006 to December 2012. A total of 17,555 pregnant women were screened for α-thalassemia in our prenatal screening program. Pregnancy at-risk for Hb Bart's disease was offered the choice of direct invasive testing or the non-invasive approach with serial ultrasonography. A total of 1425 at-risk couples attended the prenatal diagnosis. Three hundred ninety couples were screened at our own hospital, and the remaining 1035 couples were referred from other hospitals. Two hundred and three pregnant women chose non-invasive approach, and 1122 chose invasive testing. A total of 365 fetuses were diagnosed with Hb Bart's disease. All cases were finally confirmed by fetal DNA analysis. Eighty-two cases (22.4%) were diagnosed by chorionic villous sampling and 194 (53.2%) by amniocentesis samples. The other 89 (24.4%) cases were performed by cordocentesis. All of the affected pregnancies were terminated. Implementation of a prevention and control program accompanying with a referral system for prenatal diagnosis is technically feasible in Guangxi Zhuang Autonomous Region, China. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  1. Acute Sickle Hepatic Crisis after Liver Transplantation in a Patient with Hb SC Disease

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    J. H. Gillis


    Full Text Available Acute sickle hepatic crisis (ASHC has been observed in approximately 10% of patients with sickle cell disease. It occurs predominantly in patients with homozygous (Hb SS sickle cell anemia and to a lesser degree in patients with Hb SC disease, sickle cell trait, and Hb S beta thalassemia. Patients commonly present with jaundice, right upper quadrant pain, nausea, low-grade fever, tender hepatomegaly, and mild to moderate elevations in serum AST, ALT, and bilirubin. We describe the case of a patient with a history of hemoglobin SC disease and cirrhosis caused by hepatitis C presenting approximately 1 year after liver transplantation with an ASHC. The diagnosis was confirmed by liver biopsy. Our patient was treated with RBC exchange transfusions, IV hydration, and analgesia and made a complete recovery. Only a limited number of patients with sickle cell disease have received liver transplants, and, to our knowledge, this is the first case of ASHC after transplantation in a patient with Hb SC disease.

  2. The Haber Bosch-harmful algal bloom (HB-HAB) link

    NARCIS (Netherlands)

    Glibert, P.M.; Maranger, R.; Sobota, D.J.; Bouwman, Lex


    Large-scale commercialization of the Haber–Bosch (HB) process is resulting in intensification of nitrogen (N) fertilizer use worldwide. Globally N fertilizer use is far outpacing that of phosphorus (P) fertilizer. Much of the increase in N fertilizers is also now in the form of urea, a reduced form

  3. Effects of HB-EGF and epiregulin on wound healing of gingival cells in vitro. (United States)

    Kim, J M; Bak, E J; Chang, J Y; Kim, S-T; Park, W-S; Yoo, Y-J; Cha, J-H


    Gingival wound healing is important to periodontal disease and surgery. This in vitro study was conducted to assess the manner in which heparin-binding epidermal growth factor-like growth factor (HB-EGF) and epiregulin cooperatively participate in the wound-healing process in the gingival epithelial and fibroblast cells of the oral mucosa. Gingival epithelium and fibroblast were separated from gingival tissue biopsies and prepared to primary cultures. The changes in the mRNA expression were evaluated via real-time PCR. The effects on cell proliferation, migration, and repopulation were evaluated in vitro. The different regulation of expressions of HB-EGF, epiregulin, and epidermal growth factor receptors was observed over time and with different gingival cell types. HB-EGF exerted a cell migration-inducing effect on both epithelial and fibroblast cells, whereas epiregulin did not. Both growth factors functioned as mitogens for epithelial cell proliferation, but not for fibroblast proliferation. HB-EGF strongly promoted epithelial cell repopulation and mildly promoted fibroblast repopulation, whereas epiregulin promoted only fibroblast repopulation. These results indicated that both growth factors might function importantly in the wound-healing process of human gingival tissue via the different regulation of the expression, cell migration, proliferation, and repopulation. © 2011 John Wiley & Sons A/S.

  4. (HbA1c) levels with Iinsulin resistance in obese children.

    African Journals Online (AJOL)

    Objectives: We investigated the relationship between insulin resistance reflected by homeostasis model assessment (HOMA- ... Anthropometric measures and biochemical tests (fasting glucose, fasting insulin, HbA1c) were performed on all subjects. Plasma glucose ... at -70 °C. Plasma glucose levels were measured by the.

  5. (HbA1c) levels with Iinsulin resistance in obese children.

    African Journals Online (AJOL)

    Objectives: We investigated the relationship between insulin resistance reflected by homeostasis model assessment (HOMA-IR) index and serum HbA1c levels of obese children. Material and Methods: This study included 70 obese and 60 normal weight healthy children between the ages of 3 and 15. Anthropometric ...

  6. Predicting steady-state HbA1c responses to sitagliptin in patients with type 2 diabetes mellitus. (United States)

    Kanazu, S; Horie, Y; Narukawa, M; Nonaka, K; Taniguchi, T; Arjona Ferreira, J C; Takeuchi, M


    To develop predictive formulas using short-term changes in glycaemic parameters [haemoglobin A1c (HbA1c) and fasting plasma glucose (FPG)] with sitagliptin, a highly selective dipeptidyl peptidase-4 inhibitor, to assess longer term steady-state changes in HbA1c. Results from two, 12-week, double-blind studies of sitagliptin in Japanese patients with type 2 diabetes mellitus receiving once-daily sitagliptin 100 mg were used to construct linear models to develop predictive formulas based on study 1 (S1) and to validate them using study 2 (S2). HbA1c and FPG were the primary and the key secondary end-point for both studies and were both used to develop predictive formulas. The predictive formulas using HbA1c+/-FPG results (slope of change) from week 0 to week 4 in S1 showed high correlations between fitted and observed week 12 HbA1c: for HbA1c alone R2=0.76, for HbA1c+FPG R2=0.89. When using the sitagliptin 100 mg group of S2 data set to assess the validity of the predictive formulas, high correlations for HbA1c alone (R2=0.76) and for HbA1c+FPG (R2=0.77) were also observed. Data using a lower dose (25 mg once daily) of sitagliptin also demonstrated similar results. The early responses (over 4 weeks) in HbA1c and FPG with sitagliptin can be used to accurately predict later responses (at week 12) in HbA1c in Japanese patients with type 2 diabetes mellitus. Additional studies applying this approach to other agents with diverse mechanisms are important.

  7. HB tag modules for PCR-based gene tagging and tandem affinity purification in Saccharomyces cerevisiae. (United States)

    Tagwerker, Christian; Zhang, Hongwei; Wang, Xiaorong; Larsen, Liza S Z; Lathrop, Richard H; Hatfield, G Wesley; Auer, Bernhard; Huang, Lan; Kaiser, Peter


    We have recently developed the HB tag as a useful tool for tandem-affinity purification under native as well as fully denaturing conditions. The HB tag and its derivatives consist of a hexahistidine tag and a bacterially-derived in vivo biotinylation signal peptide, which support sequential purification by Ni2+ -chelate chromatography and binding to immobilized streptavidin. To facilitate tagging of budding yeast proteins with HB tags, we have created a series of plasmids with various selectable markers. These plasmids allow single-step PCR-based tagging and expression under control of the endogenous promoters or the inducible GAL1 promoter. HB tagging of several budding yeast ORFs demonstrated efficient biotinylation of the HB tag in vivo by endogenous yeast biotin ligases. No adverse effects of the HB tag on protein function were observed. The HB tagging plasmids presented here are related to previously reported epitope-tagging plasmids, allowing PCR-based tagging with the same locus-specific primer sets that are used for other widely used epitope-tagging strategies. The Sequences for the described plasmids were submitted to GenBank under Accession Numbers DQ407918-pFA6a-HBH-kanMX6 DQ407927-pFA6a-RGS18H-kanMX6 DQ407919-pFA6a-HBH-hphMX4 DQ407928-pFA6a-RGS18H-hphMX4 DQ407920-pFA6a-HBH-TRP1 DQ407929-pFA6a-RGS18H-TRP1 DQ407921-pFA6a-HTB-kanMX6 DQ407930-pFA6a-kanMX6-PGAL1-HBH DQ407922-pFA6a-HTB-hphMX4 DQ407931-pFA6a-TRP1-PGAL1-HBH DQ407923-pFA6a-HTB-TRP1 DQ407924-pFA6a-BIO-kanMX6 DQ407925-pFA6a-BIO-hphMX4 DQ407926-pFA6a-BIO-TRP1. Copyright 2006 John Wiley & Sons, Ltd.

  8. A Mosaic Expression of a Hb J-Amiens (HBB: c.54G > T; p.Lys18Asn) and its Interference with Hb A1c Analysis. (United States)

    Schiemsky, Toon; Van Hoovels, Lieve; Desmet, Koen J O; Phylipsen, Marion; Harteveld, Cornelis L; Kieffer, Davy M J


    We report the case of a 56-year-old Caucasian woman in whom hemoglobinopathy screening was triggered following an aberrant Hb A1c analysis. Preliminary diagnosis of the hemoglobin (Hb) variant was obtained through cation exchange high performance liquid chromatography (HPLC) and gel electrophoresis. DNA analysis confirmed the presence of Hb J-Amiens [β17(A14)Lys→Asn; HBB: c.[54G > C or 54G > T)]. However, an unbalanced ratio between wild type and mutant signal after direct sequencing and a lower than expected percentage of this Hb variant led to the suggestion of a mosaic expression. Furthermore, different methods [capillary zone electrophoresis (CZE), cation exchange HPLC and boronate affinity] were tested to study the possible interference of this variant with Hb A1c measurements. These investigations showed a clinically relevant difference between the methods tested. Hb A1c analysis may lead to the discovery of new Hb variants or mosaicism for previously described Hb variants. This may have genetic consequences for the offspring of carriers and brings about the question of partner testing.

  9. Mild Microcytic Anemia in an Infant with a Compound Heterozygosity for Hb C (HBB: c.19G > A) and Hb Osu Christiansborg (HBB: c.157G > A). (United States)

    Boucher, Maria O; Chui, David H K; Woda, Bruce A; Newburger, Peter E


    We report an infant with a compound heterozygosity for Hb C (HBB: c.19G > A) and Hb Osu Christiansborg (HBB: c.157G > A) and a phenotype of mild microcytic anemia with target cell morphology but without overt hemolysis.

  10. Hb level, iron intake and mortality in Chinese adults: a 10-year follow-up study. (United States)

    Shi, Zumin; Zhen, Shiqi; Zhou, Yonglin; Taylor, Anne W


    Anaemia is prevalent in developing countries and is commonly Fe deficiency related. We aimed to assess the association between Fe status, Fe intake and mortality among Chinese adults. We prospectively studied 8291 adults aged 20-98 years with a mean follow-up of 9·9 years. All participants were measured for Hb at baseline in 2002. Food intake, measured by 3-d weighed food record (n 2832), and fasting serum ferritin were measured. We documented 491 deaths (including 192 CVD and 165 cancer deaths) during 81 527 person-years of follow-up. There was a U-shaped association between Hb levels and all-cause mortality. Compared with the second quartile of Hb (121 g/l), the first (105) and fourth quartile (144) had hazard ratios (HR) of 2·29 (95 % CI 1·51, 3·48) and 2·31 (95 % CI 1·46, 3·64) for all-cause mortality in women. In men, compared with third quartile of Hb (143 g/l), first (122) and fourth quartiles (154) had 61 and 65 % increased risk of all-cause mortality. Anaemia was associated with an increased risk of all-cause and CVD mortality in men but not in women after adjusting for potential confounders. Low and high Fe intake as percentage of Chinese recommended nutrient intake (RNI) were positively associated with all-cause mortality in women but not in men. In women, across quartiles of relative Fe intake, HR for all-cause mortality were 2·55 (95 % CI 0·99, 6·57), 1·00, 3·12 (95 % CI 1·35, 7·18) and 2·78 (95 % CI 1·02, 7·58). Both low and high Hb levels are related to increased risk of all-cause mortality. Both low and high intake of Fe as percentage of RNI was positively associated with mortality in women.

  11. Critical factors in the chromatographic measurement of glycohemoglobin (HbA1). (United States)

    Simon, M; Eissler, J


    Measurement of glycohemoglobin has been proposed as a criterion for the management of diabetes mellitus. We evaluated various conditions critical to the accuracy and precision of the cation-exchange method. Tolerance limits for each variable were defined as follows: phosphate-eluding buffer (0.06 +/- 0.005 mol/L pH 6.70--6.72), column temperature (19--21 degrees C), and resin equilibration (to phosphate buffer, 0.07 mol/l, pH 6.70 +/- 0.01). Hemoglobin absorbance measured in the Sorét region (approximately 416 nm) of the first chromatographic fraction divided by that of the total hemolysate provided the most accurate and precise result. Overall between-run precision expressed as coefficient of variation (CV, in percent) of normal and diabetic pools was 4.8% and 5.1%, respectively. When purified HbA1c was added to hemolysates, recovery was 90--95%. Results were linear to at least 18% glycohemoglobin. Hemoglobin F (HbF) interfered with the method, whereas HbC and HbS did not. Red cells could be stored frozen for at least 6 days, thus easing transport of outpatient samples. A reference range of 6.0--8.8% glycohemoglobin was established from 85 nondiabetic adults (ages 23--65 yr). In a clinical study, only 4 of 13 treated diabetic patients believed to be in good control showed glycohemoglobin results within the normal range. All of the 19 treated diabetics in fair or poor control showed glycohemoglobin results greater than 10% of total Hb, ie., well above the normal range.

  12. Symposium by NATO Defense Research Group Panel VIII on Computer-Based Instruction in Military Environments

    CERN Document Server

    Weddle, Peter


    This collection of papers is the result of a symposium sponsored by NATO's Defense Research Group Panel VIII in the Spring of 1985. The symposium came into being when it became obvious to the NATO countries that research, development and utilization of advanced technologies for training was the best means of increasing both training effectiveness and efficiency. This symposium was the second in a series of three devoted to training. The series was structured to cover all aspects of training. The first series addressed the value of training, the second one dealt with the application of training technologies and the third and last of the series focused on academic issues concerned with the effect of prior learning on subsequent learning. The fact that a major American publisher has determined that computer based instruction is the technology of greatest interest to the NATO community is not surprising. Advances in microprocessor technology have revolutionized both how and where we train. During this symposium t...


    Directory of Open Access Journals (Sweden)

    Haeruddin Niva


    Full Text Available The objectives of the research are: (i to know the prosocial behavioral level of the students in Bosowa International School Makassar before and after giving cinematography approach, and (ii to know whether or not the approach is able to enhance the prosocial behavior of the students in Bosowa International School Makassar. The research is a quantitative research using experimental method. The research design used is quasi experimental design with non-equivalent control group design. The data collection technique applied is scale and FGD (Focus Group Discussion. The findings shows that (i the prosocial behavioral level of the students was low in pretest while after giving treatment there were significant increase to the prosocial behavior in the experimental group, and (ii the cinematography approach was able to increase the prosocial behavior of the Grade VIII students in Bosowa Internatinal School Makassar. 

  14. Naked DNA transfer of Factor VIII induced transgene-specific, species-independent immune response in hemophilia A mice. (United States)

    Ye, Peiqing; Thompson, Arthur R; Sarkar, Rita; Shen, Zhenping; Lillicrap, David P; Kaufman, Randal J; Ochs, Hans D; Rawlings, David J; Miao, Carol H


    The development of antibodies to a previously unexpressed protein product may limit the success of human gene therapy approaches. We inserted B-domain-deleted factor VIII (FVIII) cDNA of human, canine, or murine origin into the multiple cloning site of a liver-specific vector, pBS-HCRHPI-A, to yield plasmids pBS-HCRHPI-FVIIIA, pBS-HCRHPI-cFVIIIA, and pBS-HCRHPI-mFVIIIA, respectively. Fifty micrograms of each plasmid in 2 ml of solution was rapidly injected into the tail vein of three groups of hemophilia A mice. Factor VIII levels ranging from 3 to 12 IU/ml were obtained from all three groups (normal is 1 IU/ml in human plasma) 3 days after treatment. These initial very high levels of functional human, canine, or murine factor VIII, however, fell gradually to undetectable levels within 2-3 weeks, and their disappearance correlated with the generation of high-titer, inhibitory anti-FVIII antibodies. Notably, this immune response occurred independent of the species of origin of the exogenous factor VIII. Antibody titers to factor VIII were detected beginning at 2 weeks, reached a plateau and remained at high levels for over 6 months. The majority of anti-hFVIII IgG was IgG1 isotype specific, suggesting a humoral response mediated by Th2-induced signals. Consistent with this idea, in a separate group of mice treated with pBS-HCRHPI-FVIIIA, transient immunosuppression by cyclophosphamide significantly delayed (5/6) or abolished (1/6) inhibitory antibody formation against the transgene.

  15. Molecular Analysis of Factor VIII and Factor IX Genes in Hemophilia Patients: Identification of Novel Mutations and Molecular Dynamics Studies (United States)

    Al-Allaf, Faisal A.; Taher, Mohiuddin M.; Abduljaleel, Zainularifeen; Bouazzaoui, Abdellatif; Athar, Mohammed; Bogari, Neda M.; Abalkhail, Halah A.; Owaidah, Tarek MA.


    Background Hemophilias A and B are X-linked bleeding disorders caused by mutations in the factor VIII and factor IX genes, respectively. Our objective was to identify the spectrum of mutations of the factor VIII and factor IX genes in Saudi Arabian population and determine the genotype and phenotype correlations by molecular dynamics (MD) simulation. Methods For genotyping, blood samples from Saudi Arabian patients were collected, and the genomic DNA was amplified, and then sequenced by Sanger method. For molecular simulations, we have used softwares such as CHARMM (Chemistry at Harvard Macromolecular Mechanics; and GROMACS. In addition, the secondary structure was determined based on the solvent accessibility for the confirmation of the protein stability at the site of mutation. Results Six mutations (three novel and three known) were identified in factor VIII gene, and six mutations (one novel and five known) were identified in factor IX gene. The factor VIII novel mutations identified were c.99G>T, p. (W33C) in exon 1, c.2138 DelA, p. (N713Tfs*9) in eon14, also a novel mutation at splicing acceptor site of exon 23 c.6430 - 1G>A. In factor IX, we found a novel mutation c.855G>C, p. (E285D) in exon 8. These novel mutations were not reported in any factor VIII or factor IX databases previously. The deleterious effects of these novel mutations were confirmed by PolyPhen2 and SIFT programs. Conclusion The protein functional and structural studies and the models built in this work would be appropriate for predicting the effects of deleterious amino acid substitutions causing these genetic disorders. These findings are useful for genetic counseling in the case of consanguineous marriages which is more common in the Saudi Arabia. PMID:28270892

  16. Molecular Analysis of Factor VIII and Factor IX Genes in Hemophilia Patients: Identification of Novel Mutations and Molecular Dynamics Studies. (United States)

    Al-Allaf, Faisal A; Taher, Mohiuddin M; Abduljaleel, Zainularifeen; Bouazzaoui, Abdellatif; Athar, Mohammed; Bogari, Neda M; Abalkhail, Halah A; Owaidah, Tarek Ma


    Hemophilias A and B are X-linked bleeding disorders caused by mutations in the factor VIII and factor IX genes, respectively. Our objective was to identify the spectrum of mutations of the factor VIII and factor IX genes in Saudi Arabian population and determine the genotype and phenotype correlations by molecular dynamics (MD) simulation. For genotyping, blood samples from Saudi Arabian patients were collected, and the genomic DNA was amplified, and then sequenced by Sanger method. For molecular simulations, we have used softwares such as CHARMM (Chemistry at Harvard Macromolecular Mechanics; and GROMACS. In addition, the secondary structure was determined based on the solvent accessibility for the confirmation of the protein stability at the site of mutation. Six mutations (three novel and three known) were identified in factor VIII gene, and six mutations (one novel and five known) were identified in factor IX gene. The factor VIII novel mutations identified were c.99G>T, p. (W33C) in exon 1, c.2138 DelA, p. (N713Tfs*9) in eon14, also a novel mutation at splicing acceptor site of exon 23 c.6430 - 1G>A. In factor IX, we found a novel mutation c.855G>C, p. (E285D) in exon 8. These novel mutations were not reported in any factor VIII or factor IX databases previously. The deleterious effects of these novel mutations were confirmed by PolyPhen2 and SIFT programs. The protein functional and structural studies and the models built in this work would be appropriate for predicting the effects of deleterious amino acid substitutions causing these genetic disorders. These findings are useful for genetic counseling in the case of consanguineous marriages which is more common in the Saudi Arabia.

  17. Hb H disease resulting from the association of an αº-thalassemia allele [-(α20.5] with an unstable α-globin variant [Hb Icaria]: first report on the occurrence in Brazil

    Directory of Open Access Journals (Sweden)

    Elza M. Kimura


    Full Text Available Hb H Disease is caused by the loss or inactivation of three of the four functional a-globin genes. Patients present chronic hemolytic anemia and splenomegaly. In some cases, occasional blood transfusions are required. Deletions are the main cause of this type of thalassemia (α-thalassemia. We describe here an unusual case of Hb H disease caused by the combination of a common αº deletion [-(α20.5] with a rare point mutation (c.427T > A, thus resulting in an elongated and unstable α-globin variant, Hb Icaria, (X142K, with 31 additional amino-acid residues. Very high levels of Hb H and Hb Bart's were detected in the patient's red blood cells (14.7 and 19.0%, respectively. This is the first description of this infrequent association in the Brazilian population.

  18. Bioengineered coagulation factor VIII enables long-term correction of murine hemophilia A following liver-directed adeno-associated viral vector delivery

    Directory of Open Access Journals (Sweden)

    Harrison C Brown


    Full Text Available Clinical data support the feasibility and safety of adeno-associated viral (AAV vectors in gene therapy applications. Despite several clinical trials of AAV-based gene transfer for hemophilia B, a unique set of obstacles impede the development of a similar approach for hemophilia A. These include (i the size of the factor VIII (fVIII transgene, (ii humoral immune responses to fVIII, (iii inefficient biosynthesis of human fVIII, and (iv AAV vector immunity. Through bioengineering approaches, a novel fVIII molecule, designated ET3, was developed and shown to improve biosynthetic efficiency 10- to 100-fold. In this study, the utility of ET3 was assessed in the context of liver-directed, AAV-mediated gene transfer into hemophilia A mice. Due to the large size of the expression cassette, AAV-ET3 genomes packaged into viral particles as partial genome fragments. Despite this potential limitation, a single peripheral vein administration of AAV-ET3 into immune-competent hemophilia A mice resulted in correction of the fVIII deficiency at lower vector doses than previously reported for similarly oversized AAV-fVIII vectors. Therefore, ET3 appears to improve vector potency and mitigate at least one of the critical barriers to AAV-based clinical gene therapy for hemophilia A.

  19. Factor VIII brand and the incidence of factor VIII inhibitors in previously untreated UK children with severe hemophilia A, 2000-2011. (United States)

    Collins, Peter W; Palmer, Benedict P; Chalmers, Elizabeth A; Hart, Daniel P; Liesner, Ri; Rangarajan, Savita; Talks, Katherine; Williams, Michael; Hay, Charles R M


    The effect of recombinant factor VIII (rFVIII) brand on inhibitor development was investigated in all 407 severe hemophilia A previously untreated patients born in the United Kingdom (UK) between 1 January 2000 and 31 December 2011. Eighty-eight (22%) had been in the RODIN study. Information was extracted from the National Haemophilia Database. Because exposure days (EDs) were not known for some patients, time from first treatment was used as a surrogate for rFVIII exposure. An inhibitor developed in 118 (29%) patients, 60 high and 58 low titer, after a median (interquartile range) of 7.8 (3.3-13.5) months from first exposure and 16 (9-30) EDs. Of 128 patients treated with Kogenate Bayer/Helixate NexGen, 45 (35.2%, 95% confidence interval [CI] 27.4-43.8) developed an inhibitor compared with 42/172 (24.4%, 95% CI 18.6% to 31.4%) with Advate (P = .04). The adjusted hazard ratio (HR) (95% CI) for Kogenate Bayer/Helixate NexGen compared with Advate was 2.14 (1.12-4.10) (P = .02) for high titer and 1.75 (1.11-2.76) (P = .02) for all inhibitors. When excluding UK-RODIN patients, the adjusted HR (95% CI) for high-titer inhibitors was 2.00 (0.93-4.34) (P = .08). ReFacto AF was associated with a higher incidence of all, but not high-titer, inhibitors than Advate. These results will help inform debate around the relative immunogenicity and use of rFVIII brands. © 2014 by The American Society of Hematology.

  20. Anti-CD3 antibodies modulate anti-factor VIII immune responses in hemophilia A mice after factor VIII plasmid-mediated gene therapy. (United States)

    Peng, Baowei; Ye, Peiqing; Rawlings, David J; Ochs, Hans D; Miao, Carol H


    One major obstacle in gene therapy is the generation of immune responses directed against transgene product. Five consecutive anti-CD3 treatments concomitant with factor VIII (FVIII) plasmid injection prevented the formation of inhibitory antibodies against FVIII and achieved persistent, therapeutic levels of FVIII gene expression in treated hemophilia A mice. Repeated plasmid gene transfer is applicable in tolerized mice without eliciting immune responses. Anti-CD3 treatment significantly depleted both CD4+ and CD8+ T cells, whereas increased transforming growth factor-beta levels in plasma and the frequency of both CD4+CD25+FoxP3+ and CD4+CD25-Foxp3+ regulatory T cells in the initial few weeks after treatment. Although prior depletion of CD4+CD25+ cells did not abrogate tolerance induction, adoptive transfer of CD4+ cells from tolerized mice at 6 weeks after treatment protected recipient mice from anti-FVIII immune responses. Anti-CD3-treated mice mounted immune responses against both T-dependent and T-independent neo-antigens, indicating that anti-CD3 did not hamper the immune systems in the long term. Concomitant FVIII plasmid + anti-CD3 treatment induced long-term tolerance specific to FVIII via a mechanism involving the increase in transforming growth factor-beta levels and the generation of adaptive FVIII-specific CD4+Foxp3+ regulatory T cells at the periphery. Furthermore, anti-CD3 can reduce the titers of preexisting anti-FVIII inhibitory antibodies in hemophilia A mice.

  1. New diagnostic criteria for diabetes: is the change from glucose to HbA1c possible in all populations?

    DEFF Research Database (Denmark)

    Jørgensen, Marit Eika; Bjerregaard, Peter; Borch-Johnsen, Knut


    Recently, a change of the diagnostic tool for diabetes from an oral glucose tolerance test (OGTT) to hemoglobin A1c (HbA1c) has been suggested. The aim of the study was to assess whether ethnicity modified the association between glucose levels and HbA1c and to compare diabetes prevalence according...

  2. A Plan to Close the Achievement Gap for African American Students. Final Report. Submitted by the HB2722 Advisory Committee (United States)

    Washington Office of Superintendent of Public Instruction, 2008


    In 2008, the Washington State Legislature passed HB 2722, which called for the appointment of an Advisory Committee charged with creating a plan--which, when fully implemented, will close the education gap for African American students. Beginning in May 2008, the newly appointed HB 2722 Advisory Committee took on this challenging charge. Early in…

  3. Role of HbA1c in post-partum screening of women with gestational diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Rickard Claesson


    Conclusion: Proposed thresholds of HbA1c had low diagnostic sensitivity. Combined with a fasting glucose test, the performance was no better than with using a fasting glucose test alone. Combining a fasting glucose test with a lower HbA1c cut-point may be an alternative approach for selection of women for an OGTT.

  4. Translating HbA1c measurements into estimated average glucose values in pregnant women with diabetes

    DEFF Research Database (Denmark)

    Law, Graham R; Gilthorpe, Mark S; Secher, Anna L


    AIMS/HYPOTHESIS: This study aimed to examine the relationship between average glucose levels, assessed by continuous glucose monitoring (CGM), and HbA1c levels in pregnant women with diabetes to determine whether calculations of standard estimated average glucose (eAG) levels from HbA1c measureme...

  5. Structural basis for the antipolymer activity of Hb ζ2β(s)2 trapped in a tense conformation. (United States)

    Safo, Martin K; Ko, Tzu-Ping; Schreiter, Eric R; Russell, J Eric


    The phenotypical severity of sickle-cell disease (SCD) can be mitigated by modifying mutant hemoglobin S (Hb S, Hb α2β(s)2) to contain embryonic ζ-globin in place of adult α-globin subunits (Hb ζ2β(s)2). Crystallographical analyses of liganded Hb ζζ2β(s)2, though, demonstrate a tense (T-state) quaternary structure that paradoxically predicts its participation in--rather than its exclusion from--pathological deoxyHb S polymers. We resolved this structure-function conundrum by examining the effects of α→ζ exchange on the characteristics of specific amino acids that mediate sickle polymer assembly. Superposition analyses of the β(s) subunits of T-state deoxyHb α2β(s)2 and T-state CO-liganded Hb ζ2β(s)2 reveal significant displacements of both mutant β(s)Val6 and conserved β-chain contact residues, predicting weakening of corresponding polymer-stabilizing interactions. Similar comparisons of the α- and ζ-globin subunits implicate four amino acids that are either repositioned or undergo non-conservative substitution, abrogating critical polymer contacts. CO-Hb ζ2β(s)2 additionally exhibits a unique trimer-of-heterotetramers crystal packing that is sustained by novel intermolecular interactions involving the pathological β(s)Val6, contrasting sharply with the classical double-stranded packing of deoxyHb S. Finally, the unusually large buried solvent-accessible surface area for CO-Hb ζ2β(s)2 suggests that it does not co-assemble with deoxyHb S in vivo. In sum, the antipolymer activities of Hb ζ2β(s)2 appear to arise from both repositioning and replacement of specific α- and β(s)-chain residues, favoring an alternate T-state solution structure that is excluded from pathological deoxyHb S polymers. These data account for the antipolymer activity of Hb ζ2β(s)2, and recommend the utility of SCD therapeutics that capitalize on α-globin exchange strategies.

  6. Analytical verification and quality assessment of the Tosoh HLC-723GX HbA1c analyzer

    Directory of Open Access Journals (Sweden)

    Marko Ris


    Full Text Available Objectives: Ion-exchange high-performance liquid chromatography (IE-HPLC has long been used as a reproducible and versatile analytical tool for HbA1c measurement.In this study, we performed analytical verification and quality assessment of the recently introduced small IE-HPLC Tosoh HLC-723GX HbA1c analyzer, and a comparison of results to immunoassay (IA and capillary electrophoresis (CE. Design and methods: The total imprecision of Tosoh HLC-723GX was verified according to CLSI EP15-A2 protocol using commercial control materials (C-QC and pooled human whole blood samples (HWB. The Sigma metric was used for the evaluation of quality targets. HbA1c results were compared to automated CE (MiniCap Flex Piercing, Sebia, France and IA (Tina-quant HbA1c Gen 2, Cobas Integra 400+, Roche Diagnostics, USA procedures. Results: The total imprecision of Tosoh HLC-723GX-HbA1c for IFCC(mmol/mol and NGSP(% units was: 1.91/1.25% (HbA1c=31 mmol/mol/5.0% and 0.51/0.63% (HbA1c=84 mmol/mol/9.8% for C-QC, and 0.39/0.2% (HbA1c=47 mmol/mol/6.5% and 0.77/0.46% (HbA1c=94 mmol/mol/10.8% in HWB samples, respectively. Bland-Altman analysis did not reveal any deviation of the results between Tosoh HLC-723GX and CE: mean difference 0.0% (95%CI: −0.02927 to 0.02653%, while the mean HbA1c difference against IA was −0.07% (95%CI: −0.1039 to −0.02765. At the selected HbA1c clinical decision level (48 mmol/mol/6,5%, six sigma analysis gave σ value of 3.91, within a desirable classification of performance. Conclusion: The analytical performance of the Tosoh HLC-723GX complies with the rigorous quality criteria for clinical use of HbA1c, with the results comparable to the CE procedure. Tosoh HLC-723GX provides a plausible analytical choice for reliable HbA1c measurement in low-volume laboratories. Keywords: HbA1c, Quality targets, Six sigma, Tosoh HLC-723GX analyzer

  7. [Noninvasive prenatal diagnosis of Hb Bart's hydrops fetus using cell-free fetal DNA in maternal plasma]. (United States)

    Long, Xing-Jiang; Long, Gui-Fang; Lin, Wei-Xiong


    To explore a new noninvasive method for Hb Bart' s hydrops fetus by using PCR amplification efficiency discrimination between cell-free fetal DNA (cffDNA) and cell-free maternal DNA in maternal plasma. CffDNA samples from pregnant women bearing possible Hb Bart's hydrops fetus were collected. Fluorescent PCR and capillary electrophoresis (CE) were performed. Hb Bart's hydrops fetus was conclusively identified by different peak area ratio of products. The peak area ratio of 30 cffDNA samples from Hb Bart' s hydrops fetus was much less than 1. However, the ratio of cffDNA sample from hydrops fetus due to other reasons was approximately equal to 1. By using cffDNA fluorescent PCR and CE, a prenatal screening method for Hb Bart' s hydrops fetus was developed.

  8. Identification, Functional Study, and Promoter Analysis of HbMFT1, a Homolog of MFT from Rubber Tree (Hevea brasiliensis). (United States)

    Bi, Zhenghong; Li, Xiang; Huang, Huasun; Hua, Yuwei


    A homolog of MOTHER OF FT AND TFL1 (MFT) was isolated from Hevea brasiliensis and its biological function was investigated. Protein multiple sequence alignment and phylogenetic analysis revealed that HbMFT1 conserved critical amino acid residues to distinguish MFT, FLOWERING LOCUS T (FT) and TERMINAL FLOWER1 (TFL1)-like proteins and showed a closer genetic relationship to the MFT-like group. The accumulation of HbMFT1 was generally detected in various tissues except pericarps, with the highest expression in embryos and relatively higher expression in roots and stems of seedlings, flowering inflorescences, and male and female flowers. HbMFT1 putative promoter analysis showed that tissue-specific, environmental change responsive and hormone-signaling responsive elements were generally present. HbMFT1 was strongly induced under a short-day condition at 28 °C, with the highest expression after the onset of a day. Overexpression of HbMFT1 inhibited seed germination, seedling growth, and flowering in transgenic Arabidopsis. The qRT-PCR further confirmed that APETALA1 (AP1) and FRUITFULL (FUL) were drastically down-regulated in 35S::HbMFT1 plants. A histochemical β-glucuronidase (GUS) assay showed that HbMFT1::GUS activity was mainly detected in stamens and mature seeds coinciding with its original expression and notably induced in rosette leaves and seedlings of transgenic Arabidopsis by exogenous abscisic acid (ABA) due to the presence of ABA cis-elements in HbMFT1 promoter. These results suggested that HbMFT1 was mainly involved in maintenance of seed maturation and stamen development, but negatively controlled germination, growth and development of seedlings and flowering. In addition, the HbMFT1 promoter can be utilized in controlling transgene expression in stamens and seeds of rubber tree or other plant species.

  9. High Frequency of Hb E-Saskatoon (HBB: c.67G > A) in Brazilians: A New Genetic Origin? (United States)

    Wagner, Sandrine C; Lindenau, Juliana D; Castro, Simone M de; Santin, Ana Paula; Zaleski, Carina F; Azevedo, Laura A; Ribeiro Dos Santos, Ândrea K C; Dos Santos, Sidney E B; Hutz, Mara H


    Hb E-Saskatoon [β22(B4)Glu→Lys, HBB: c.67G > A] is a rare, nonpathological β-globin variant that was first described in a Canadian woman of Scottish and Dutch ancestry and has since then been detected in several populations. The aim of the present study was to identify the origin of Hb E-Saskatoon in Brazil using β-globin haplotypes and genetic ancestry in carriers of this hemoglobin (Hb) variant. Blood samples were investigated by isoelectric focusing (IEF) and high performance liquid chromatography (HPLC) using commercial kits. Hb E-Saskatoon was confirmed by amplification of the HBB gene, followed by sequence analysis. Haplotypes of the β-globin gene were determined by polymerase chain reaction (PCR), followed by digestion with specific restriction enzymes. Individual ancestry was estimated with 48 biallelic insertion/deletions using three 16-plex PCR amplifications. The IEF pattern was similar to Hbs C (HBB: c.19G > A) and Hb E (HBB: c.79G > A) [isoelectric point (pI): 7.59-7.65], and HPLC results showed an elution in the Hb S (HBB: c.20A > T) window [retention time (RT): 4.26-4.38]. DNA sequencing of the amplified β-globin gene showed a mutation at codon 22 (GAA>AAA) corresponding to Hb E-Saskatoon. A total of 11 cases of this variant were identified. In nine unrelated individuals, Hb E-Saskatoon was in linkage disequilibrium with haplotype 2 [+ - - - -]. All subjects showed a high degree of European contribution (mean = 0.85). Hb E-Saskatoon occurred on the β-globin gene of haplotype 2 in all Brazilian carriers. These findings suggest a different genetic origin for this Hb variant from that previously described.

  10. Identification, Functional Study, and Promoter Analysis of HbMFT1, a Homolog of MFT from Rubber Tree (Hevea brasiliensis

    Directory of Open Access Journals (Sweden)

    Zhenghong Bi


    Full Text Available A homolog of MOTHER OF FT AND TFL1 (MFT was isolated from Hevea brasiliensis and its biological function was investigated. Protein multiple sequence alignment and phylogenetic analysis revealed that HbMFT1 conserved critical amino acid residues to distinguish MFT, FLOWERING LOCUS T (FT and TERMINAL FLOWER1 (TFL1-like proteins and showed a closer genetic relationship to the MFT-like group. The accumulation of HbMFT1 was generally detected in various tissues except pericarps, with the highest expression in embryos and relatively higher expression in roots and stems of seedlings, flowering inflorescences, and male and female flowers. HbMFT1 putative promoter analysis showed that tissue-specific, environmental change responsive and hormone-signaling responsive elements were generally present. HbMFT1 was strongly induced under a short-day condition at 28 °C, with the highest expression after the onset of a day. Overexpression of HbMFT1 inhibited seed germination, seedling growth, and flowering in transgenic Arabidopsis. The qRT-PCR further confirmed that APETALA1 (AP1 and FRUITFULL (FUL were drastically down-regulated in 35S::HbMFT1 plants. A histochemical β-glucuronidase (GUS assay showed that HbMFT1::GUS activity was mainly detected in stamens and mature seeds coinciding with its original expression and notably induced in rosette leaves and seedlings of transgenic Arabidopsis by exogenous abscisic acid (ABA due to the presence of ABA cis-elements in HbMFT1 promoter. These results suggested that HbMFT1 was mainly involved in maintenance of seed maturation and stamen development, but negatively controlled germination, growth and development of seedlings and flowering. In addition, the HbMFT1 promoter can be utilized in controlling transgene expression in stamens and seeds of rubber tree or other plant species.

  11. Significance of HbA1c and its measurement in the diagnosis of diabetes mellitus: US experience

    Directory of Open Access Journals (Sweden)

    Juarez DT


    Full Text Available Deborah Taira Juarez, Kendra M Demaris, Roy Goo, Christina Louise Mnatzaganian, Helen Wong SmithDaniel K Inouye College of Pharmacy, University of Hawaii at Hilo, Honolulu, HI, USAAbstract: The 2014 American Diabetes Association guidelines denote four means of diagnosing diabetes. The first of these is a glycosylated hemoglobin (HbA1c >6.5%. This literature review summarizes studies (n=47 in the USA examining the significance, strengths, and limitations of using HbA1c as a diagnostic tool for diabetes, relative to other available means. Due to the relatively recent adoption of HbA1c as a diabetes mellitus diagnostic tool, a hybrid systematic, truncated review of the literature was implemented. Based on these studies, we conclude that HbA1c screening for diabetes has been found to be convenient and effective in diagnosing diabetes. HbA1c screening is particularly helpful in community-based and acute care settings where tests requiring fasting are not practical. Using HbA1c to diagnose diabetes also has some limitations. For instance, HbA1c testing may underestimate the prevalence of diabetes, particularly among whites. Because this bias differs by racial group, prevalence and resulting estimates of health disparities based on HbA1c screening differ from those based on other methods of diagnosis. In addition, existing evidence suggests that HbA1c screening may not be valid in certain subgroups, such as children, women with gestational diabetes, patients with human immunodeficiency virus, and those with prediabetes. Further guidelines are needed to clarify the appropriate use of HbA1c screening in these populations.Keywords: diabetes mellitus, diagnosis, glycosylated hemoglobin, USA


    Directory of Open Access Journals (Sweden)

    Aditya Dwi Haryawan


    Full Text Available Menulis merupakan suatu keterampilan yang harus dimiliki peserta didik sekolah menengah pertama. Melaluitulisan, peserta didik dapat menyampaikan pengalaman, pikiran, perasaan, atau keinginan. Masalah penelitianini adalah (1 bagaimanakah kebutuhan pengembangan model pembelajaran berbasis masalah yang bermuatannilai-nilai pendidikan karakter dalam pembelajaran menulis cerpen berdasarkan persepsi guru dan pesertadidik kelas VIII SMP?; (2 bagaimanakah prinsip-prinsip pengembangan model pembelajaran berbasis masalahyang bermuatan nilai-nilai pendidikan karakter dalam pembelajaran menulis cerpen pada peserta didik kelasVIII SMP? (3 bagaimanakah pengembangan prototipe model pembelajaran berbasis masalah yang bermuatannilai-nilai pendidikan karakter dalam pembelajaran menulis cerpen pada kelas VIII SMP?; (4 bagaimanakahkeberterimaan penerapan pengembangan model pembelajaran berbasis masalah yang bermuatan nilai-nilaipendidikan karakter dalam pembelajaran menulis cerpen pada kelas VIII SMP. Dalam penelitian ini digunakandesain Research and Development. Tahapan yang dilakukan dalam penelitian ini adalah studi pustaka, analisiskebutuhan, pengembangan model yang dikembangkan, uji validasi, revisi, implementasi, revisi akhir,pengembangan model/produk akhir. Pengumpulan data dilakukan dengan observasi, angket, wawancara, tes,dan dokumentasi foto. Writing is a skill that must be owned by middle school students. Through writing, students canconvey experiences, thoughts, feelings, or desires. The research problem is (1 How can the needsof the development of PBL model that charged the values of character education in learning towrite short stories on the perceptions of teachers and students of class VIII?; (2 How do thecharacteristics of the development of PBL model value-laden -the value of character education inlearning to write short stories at the high school of learner assessment system class?; (3 How isthe development of a prototype model of PBL  charged

  13. DNA studies are necessary for accurate patient diagnosis in compound heterozygosity for Hb Adana (HBA2:c.179>A) with deletional or nondeletional α-thalassaemia. (United States)

    Tan, Jin Ai Mary Anne; Kho, Siew Leng; Ngim, Chin Fang; Chua, Kek Heng; Goh, Ai Sim; Yeoh, Seoh Leng; George, Elizabeth


    Haemoglobin (Hb) Adana (HBA2:c.179>A) interacts with deletional and nondeletional α-thalassaemia mutations to produce HbH disorders with varying clinical manifestations from asymptomatic to severe anaemia with significant hepatosplenomegaly. Hb Adana carriers are generally asymptomatic and haemoglobin subtyping is unable to detect this highly unstable α-haemoglobin variant. This study identified 13 patients with compound heterozygosity for Hb Adana with either the 3.7 kb gene deletion (-α(3.7)), Hb Constant Spring (HbCS) (HBA2:c.427T>C) or Hb Paksé (HBA2:429A>T). Multiplex Amplification Refractory Mutation System was used for the detection of five deletional and six nondeletional α-thalassaemia mutations. Duplex-PCR was used to confirm Hb Paksé and HbCS. Results showed 84.6% of the Hb Adana patients were Malays. Using DNA studies, compound heterozygosity for Hb Adana and HbCS (α(codon 59)α/α(CS)α) was confirmed in 11 patients. A novel point in this investigation was that DNA studies confirmed Hb Paksé for the first time in a Malaysian patient (α(codon 59)α/α(Paksé)α) after nine years of being misdiagnosis with Hb Adana and HbCS (α(codon 59)α/α(CS)α). Thus, the reliance on haematology studies and Hb subtyping to detect Hb variants is inadequate in countries where thalassaemia is prevalent and caused by a wide spectrum of mutations.

  14. Evaluation of the Interference of Hemoglobin Variant J-Bangkok on Glycated Hemoglobin (HbA1c) Measurement by Five Different Methods. (United States)

    Wen, Dong-Mei; Xu, Sheng-Nan; Wang, Wei-Jia; Zhang, Xiu-Ming; Suo, Ming-Huan; Zhang, De-Cai


    Objective The interference of the hemoglobin variant (Hb J-Bangkok) was evaluated on 4 different glycated hemoglobin assays and compared with a reference immuno assay. Methods An overall test of coincidence of 2 least-squares linear regression lines was performed to determine whether the presence of Hb J-Bangkok caused a statistically significant difference in HbA1c results compared with a reference immuno assay. Statistical analysis was performed on the difference of the estimated average glucose calculated from HbA1c values and fasting plasma glucose in the Hb J-Bangkok variant group using the different detection systems. Deming regression analysis was used to determinate whether Hb J-Bangkok had a significant interference on HbA1c results using an HbA1c±10% relative bias at 6% and 9% HbA1c as evaluation limits. Results Turbidimetric inhibition immunoassay method, and enzymatic methods were not affected by Hb J-Bangkok. However, Hb J-Bangkok showed statistically significant interference to the two ion-exchange high-performance liquid chromatography methods. Conclusion When performing HbA1c tests, clinical laboratory personnel should identify the Hb variant and select the appropriate methods or use alternative indicators. © Georg Thieme Verlag KG Stuttgart · New York.

  15. Changing from glucose to HbA1c for diabetes diagnosis

    DEFF Research Database (Denmark)

    Nielsen, Aneta Aleksandra; Petersen, Per Hyltoft; Green, Anders


    BACKGROUND: In Denmark, the use of HbA1c in the diagnosis of diabetes was adopted from March 2012. We evaluated the change in the number of diabetes cases diagnosed by haemoglobin A1c (HbA1c) versus fasting venous plasma glucose (FPG), and estimated the influence of analytical variation and bias.......7% to 3.7% increased the number of diabetes cases by 90%. CONCLUSIONS: In the study population, the percentage of undiagnosed patients with diabetes aged 25-75 years was reduced from 3.6% (95% CI 3.0%-4.2%) based on one FPG measurement (FPG ≥7.0 mmol/L) to only 1.9% (95% CI 1.5%-2.3%) if the diagnosis...

  16. Free energy and boundary anomalies on S^a × H^b spaces (United States)

    Rodriguez-Gomez, Diego; Russo, Jorge G.


    We compute free energies as well as conformal anomalies associated with boundaries for a conformal free scalar field. To that matter, we introduce the family of spaces of the form S^a × H^b , which are conformally related to {S^a}^{+b} . For the case of a = 1, related to the entanglement entropy across {S^b}^{-1} , we provide some new explicit computations of entanglement entropies at weak coupling. We then compute the free energy for spaces S^a × H^b for different values of a and b. For spaces S^{2n+1}× H^{2k} we find an exact match with the free energy on S^{2n+2k+1} . For ℍ2 k + 1 and S^3 × H^3 we find conformal anomalies originating from boundary terms. We also compute the free energy for strongly coupled theories through holography, obtaining similar results.

  17. Production of mirrors made of HB-Cesic® for an airborne reconnaissance telescope system (United States)

    Krödel, Matthias R.; Hofbauer, Peter; Luichtel, Georg; Katzer, J.; Tausendfreund, M.; Derst, Gerhard


    In support of a new airborne telescope system the Multi-Spectral Telescope for a new Reconnaissance Program ECM was contracted by Carl Zeiss Optronics to produce 20 mirrors made of HB-Cesic®, each mirror with a diameter of 315 mm. The contract requirements were that the mirrors remain stable under extreme mechanical and thermal loads and that the production schedule is 12 months. The main challenges of the project were achieving consistent optical performance of the mirrors and meeting the tight schedule of delivering the mirrors, in lots of four, every two months for a total delivery time of twelve months. In this paper we present the lessons learned in producing the HB-Cesic® mirrors, including all the steps up to the final integration of the mirrors into the telescope system and establishing reliable repeatability of the production cycles.

  18. Ultra-lightweighted HB-Cesic one-meter mirror demonstrator (United States)

    Krödel, Matthias R.; Hofbauer, Peter


    Future space missions, such as SPICA and DARWIN, require large, light-weighted, and stiff mirrors with excellent stability. During the past years, ECM fabricated a number of light-weighted mirrors. However, future large missions require further advances with light-weighting, pushing this technology to the limit possible with recently developed composite materials, new fabrication processes, and innovative designs. In 2009, ECM took steps in this direction by fabricating successfully an ultra-lightweighted HB-Cesic® mirror demonstrator 1 m in size. We demonstrated that HB-Cesic®, due to its extreme light-weighting capability and manufacturing versatility, combined with high stiffness, high mechanical strength, and low CTE at cryogenic temperatures, is able to fully meet the requirements of future large cryogenic space mirrors. In this paper we describe the fabrication process of this demonstrator and its physical characteristics.

  19. Relationship between level of HbA1C and breast cancer

    Directory of Open Access Journals (Sweden)

    Fariba Jousheghany


    Conclusion: While there was a statistically significant association between HbA1C and obesity, there were no significant associations found with this analysis. However, there are clinically meaningful relationships based on observed trends. Future directions for research may involve exploring a larger sample of patients and the role of therapeutic regimens on blood sugar control and BMI of breast cancer patients and influence on cancer prognosis.

  20. [Effects of nitrogen and phosphorus fertilizer on atrazine degradation and detoxification by degrading strain HB-5]. (United States)

    Su, Jun; Zhu, Lu-Sheng; Li, Xu-Hua; Wang, Jun; Xie, Hui; Wang, Jin-Hua; Wang, Qi; Jia, Wen-Tao


    An atrazine-degrading strain HB-5 was used as a bacteria for biodegradation. Treatments of soil with nitrogen single, phosphate single and nitrogen phosphate together with HB-5 were carried out for degradation and eco-toxicity test; then, relationship between atrazine degradation rate and soil available nitrogen, available phosphorus were discussed. Atrazine residues were determined by HPLC; available nitrogen was determined with alkaline hydrolysis diffusion method; available phosphorus was determined with 0.5 mol/L-NaHCO3 extraction and molybdenum stibium anti-color method, and toxicity test was carried out with micronucleus test of Vicia faba root tip cells. The results showed that: After separately or together application, nitrogenous and phosphorous fertilizers could significantly accelerate atrazine degradation than soil with HB-5 only. On day 5, the order of atrazine degradation was ANP > AP > AN > A; 7 days later, no statistically significant differences were found between treatments. The available nitrogen and phosphorus level in soil reduced as the degradation rate increased in the soil. The soil of eco-toxicity test results indicated that the eco-toxicity significantly reduced with the degradation of atrazine by HB-5, and the eco-toxicity on treatments of soil with fertilizer were all below the treatments without fertilizer. On day 5, the order of eco-toxicity was ANP < AP < AN < A; 7 days later, all treatments were decreased in control levels. So, adjusting soil nutrient content could not only promote atrazine degradation in soil but also could reduce the soil eco-toxicity effects that atrazine caused. All these results could be keystone of atrazine pollution remediation in contaminated soil in the future.

  1. Fermi LAT and WMAP observations of the supernova remnant HB 21

    Energy Technology Data Exchange (ETDEWEB)

    Pivato, G. [Dipartimento di Fisica e Astronomia " G. Galilei," Università di Padova, I-35131 Padova (Italy); Hewitt, J. W. [CRESST, University of Maryland, Baltimore County, Baltimore, MD 21250 (United States); Tibaldo, L. [W. W. Hansen Experimental Physics Laboratory, Kavli Institute for Particle Astrophysics and Cosmology, Department of Physics and SLAC National Accelerator Laboratory, Stanford University, Stanford, CA 94305 (United States); Acero, F.; Brandt, T. J. [NASA Goddard Space Flight Center, Greenbelt, MD 20771 (United States); Ballet, J. [Laboratoire AIM, CEA-IRFU/CNRS/Université Paris Diderot, Service d' Astrophysique, CEA Saclay, F-91191 Gif sur Yvette (France); De Palma, F.; Giordano, F. [Dipartimento di Fisica " M. Merlin" dell' Università e del Politecnico di Bari, I-70126 Bari (Italy); Janssen, G. H. [University of Manchester, Manchester, M13 9PL (United Kingdom); Jóhannesson, G. [Science Institute, University of Iceland, IS-107 Reykjavik (Iceland); Smith, D. A., E-mail:, E-mail:, E-mail: [Centre d' Études Nucléaires de Bordeaux Gradignan, IN2P3/CNRS, Université Bordeaux 1, BP120, F-33175 Gradignan Cedex (France)


    We present the analysis of Fermi Large Area Telescope γ-ray observations of HB 21 (G89.0+4.7). We detect significant γ-ray emission associated with the remnant: the flux >100 MeV is 9.4 ± 0.8 (stat) ± 1.6 (syst) × 10{sup –11} erg cm{sup –2} s{sup –1}. HB 21 is well modeled by a uniform disk centered at l = 88.°75 ± 0.°04, b = +4.°65 ± 0.°06 with a radius of 1.°19 ± 0.°06. The γ-ray spectrum shows clear evidence of curvature, suggesting a cutoff or break in the underlying particle population at an energy of a few GeV. We complement γ-ray observations with the analysis of the WMAP 7 yr data from 23 to 93 GHz, achieving the first detection of HB 21 at these frequencies. In combination with archival radio data, the radio spectrum shows a spectral break, which helps to constrain the relativistic electron spectrum, and, in turn, parameters of simple non-thermal radiation models. In one-zone models multiwavelength data favor the origin of γ rays from nucleon-nucleon collisions. A single population of electrons cannot produce both γ rays through bremsstrahlung and radio emission through synchrotron radiation. A predominantly inverse-Compton origin of the γ-ray emission is disfavored because it requires lower interstellar densities than are inferred for HB 21. In the hadronic-dominated scenarios, accelerated nuclei contribute a total energy of ∼3 × 10{sup 49} erg, while, in a two-zone bremsstrahlung-dominated scenario, the total energy in accelerated particles is ∼1 × 10{sup 49} erg.

  2. Determination of filter pore size for use in HB line phase II production of plutonium oxide

    Energy Technology Data Exchange (ETDEWEB)

    Shehee, T. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Crowder, M. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Rudisill, T. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)


    H-Canyon and HB-Line are tasked with the production of plutonium oxide (PuO2) from a feed of plutonium (Pu) metal. The PuO2 will provide feed material for the Mixed Oxide (MOX) Fuel Fabrication Facility. After dissolution of the Pu metal in H-Canyon, plans are to transfer the solution to HB-Line for purification by anion exchange. Anion exchange will be followed by plutonium(IV) oxalate precipitation, filtration, and calcination to form PuO2. The filtrate solutions, remaining after precipitation, contain low levels of Pu ions, oxalate ions, and may include solids. These solutions are transferred to H-Canyon for disposition. To mitigate the criticality concern of Pu solids in a Canyon tank, past processes have used oxalate destruction or have pre-filled the Canyon tank with a neutron poison. The installation of a filter on the process lines from the HB-Line filtrate tanks to H-Canyon Tank 9.6 is proposed to remove plutonium oxalate solids. This report describes SRNL’s efforts to determine the appropriate pore size for the filters needed to perform this function. Information provided in this report aids in developing the control strategies for solids in the process.

  3. A reporter gene system for the precise measurement of promoter activity in Thermus thermophilus HB27. (United States)

    Fujita, Atsushi; Sato, Takaaki; Koyama, Yoshinori; Misumi, Yoshio


    We developed a reporter gene system that enables precise analysis of promoter activity in Thermus thermophilus HB27. The reporter vector employs a promoterless β-galactosidase gene of Thermus spp. strain T2. However, T. thermophilus HB27 strain has three genes (TTP0042, TTP0220 and TTP0222) whose products have β-galactosidase activity, which would interfere with correct measurements of promoter activities. Thus, to eliminate this background activity, we disrupted all three of these genes to generate a host strain for measuring promoter expression as β-galactosidase activity. In addition, T. thermophilus strains also produce carotenoids called thermoxanthins that are yellow pigments. To avoid the influence of these carotenoids on the β-galactosidase assay, we also disrupted the phytoene synthase gene (crtB). The reporter gene system developed here is a powerful tool for studying transcriptional activity and the mechanisms that regulate gene expression in T. thermophilus HB27. We also showed that the crtB gene cassette could be used in repeated gene-disruption experiments to screen transformants by colony colour, thus eliminating the need for antibiotic resistance markers.

  4. Exploring the ϒ (4 S ,5 S ,6 S )→hb(1 P )η hidden-bottom hadronic transitions (United States)

    Zhang, Yawei; Li, Gang


    Recently, the Belle Collaboration has reported the measurement of the spin-flipping transition ϒ (4 S )→hb(1 P )η with an unexpectedly large branching ratio: B (ϒ (4 S )→hb(1 P )η )=(2.18 ±0.11 ±0.18 )×10-3 . Such a large branching fraction contradicts with the anticipated suppression for the spin flip. In this work, we examine the effects induced by intermediate bottomed meson loops and point out that these effects are significantly important. Using the effective Lagrangian approach (ELA), we find the experimental data on ϒ (4 S )→hb(1 P )η can be accommodated with the reasonable inputs. We then explore the decays ϒ (5 S ,6 S )→hb(1 P )η and find that these two channels also have sizable branching fractions. We also calculate these processes in the framework of nonrelativistic effective field theory (NREFT). For the decays ϒ (4 S )→hb(1 P )η , the NREFT results are at the same order of magnitude but smaller than the ELA results by a factor of 2 to 5. For the decays ϒ (5 S ,6 S )→hb(1 P )η , the NREFT results are smaller than the ELA results by approximately 1 order of magnitude. We suggest a future experiment Belle-II to search for the ϒ (5 S ,6 S )→hb(1 P )η decays, which will be helpful for understanding the transition mechanism.

  5. Hb Heathrow [β103(G5)Phe→Leu], a First Report in an Asian Patient with Erythrocytosis. (United States)

    Shin, Sang Yong; Kim, Hyun Young; Kim, Hee Jin; Kim, Hoon Gu


    Congenital erythrocytosis (CE) is a rare and heterogeneous disease. The high oxygen affinity hemoglobin (Hb) variants are the most common cause of CE. Herein, we report a Korean patient with isolated erythrocytosis. A 25-year-old man was referred to our hospital for evaluation of high Hb level (Hb 20.4 g/dL, hematocrit 58%, reticulocyte count 2.90%, white blood cell count 6.83×10⁹/L, and platelet count 195×10⁹/L). Bone marrow biopsy revealed normocellular marrow without myeloproliferative features. JAK2 (V617F, exon 12), CALR (exon 9), and MPL W515K/L mutations were not detected. P₅₀ (partial pressure at which Hb is half saturated with oxygen), which is an indicator of left-shift of oxygen dissociation curve (high oxygen affinity state), was 14.3 mm Hg (reference value 22.6-29.4 mm Hg). He was suspected to have CE. Mutation analysis of the HBB gene revealed the known Hb variant, Hb Heathrow [β103(G5)Phe→Leu]. This is the first report of Hb Heathrow in Asian. © Copyright: Yonsei University College of Medicine 2017.

  6. Effect of combining multiple micronutrients with iron supplementation on Hb response in children: systematic review of randomized controlled trials. (United States)

    Gera, Tarun; Sachdev, Harsh Pal Singh; Nestel, Penelope


    To study the effect of combining multiple (two or more) micronutrients with Fe supplementation on Hb response, when compared with placebo and with Fe supplementation, in children. Electronic databases, personal files, hand search of reviews, bibliographies of books, and abstracts and proceedings of international conferences. Randomized controlled trials evaluating change in Hb levels with interventions that included Fe and multiple-micronutrient supplementation in comparison to placebo alone or Fe alone were analysed in two systematic reviews. Twenty-five trials were included in the review comparing Fe and micronutrient supplementation with placebo. The pooled estimate (random effects model) for change in Hb with Fe and micronutrient supplementation (weighted mean difference) was 0.65 g/dl (95 % CI 0.50, 0.80, P micronutrients' and malarial non-hyperendemic region were significant predictors of greater Hb response and heterogeneity. Thirteen trials were included in the review comparing Fe and micronutrient supplementation with Fe alone. The pooled estimate for change in Hb with Fe and micronutrient supplementation (weighted mean difference) was 0.14 g/dl (95 % CI 0.00, 0.28, P = 0.04). None of the variables were found to be significant predictors of Hb response. Synthesized evidence indicates that addition of multiple micronutrients to Fe supplementation may only marginally improve Hb response compared with Fe supplementation alone. However, addition of 'other micronutrients' may have a negative effect. Routine addition of unselected multiple micronutrients to Fe therefore appears unjustified for nutritional anaemia control programmes.

  7. HB-EGF/HER-1 signaling in bone marrow mesenchymal stem cells: inducing cell expansion and reversibly preventing multilineage differentiation. (United States)

    Krampera, Mauro; Pasini, Annalisa; Rigo, Antonella; Scupoli, Maria Teresa; Tecchio, Cristina; Malpeli, Giorgio; Scarpa, Aldo; Dazzi, Francesco; Pizzolo, Giovanni; Vinante, Fabrizio


    Epidermal growth factor receptor-1 (EGFR-1/HER-1/ErbB-1) regulates proliferation and cell fate during epidermal development. HER-1 is activated by several EGF-family ligands including heparin-binding epidermal growth factor-like growth factor (HB-EGF), a mitogenic and chemotactic molecule that participates in tissue repair, tumor growth, and other tissue-modeling phenomena, such as angiogenesis and fibrogenesis. We found that mesenchymal stem cells (MSCs), the precursors of different mesenchymal tissues with a role in processes in which HB-EGF is often involved, normally express HER-1, but not HB-EGF itself. Under the effect of HB-EGF, MSCs proliferate more rapidly and persistently, without undergoing spontaneous differentiation. This effect occurs in a dose-dependent fashion, and is specific, direct, and HER-1 mediated, as it is inhibited by anti-HER-1 and anti-HB-EGF blocking antibodies. Moreover, HB-EGF reversibly prevents adipogenic, osteogenic, and chondrogenic differentiation induced with specific media. These data show that HB-EGF/HER-1 signaling is relevant to MSC biology, by regulating both proliferation and differentiation.

  8. Standardization of HbA1c value and its comparison to immunoassay--two years of experience. (United States)

    Shiba, T; Yano, M; Maehata, E; Kiyose, H; Kotaki, Y; Fukuzawa, N; Hagura, R


    In spite of the routine use of hemoglobin Alc (HbAlc) value to guide diabetes therapy, substantial differences have been noted between results obtained by different instruments and laboratories. It was suggested that confusion between the terms used for HbA1c, i.e. between "total HbA1c' which includes labile content, and "stable HbA1c', which does not, may account for some of these inter-instrument and inter-laboratory differences. However, an undesirable difference was found even in measurements of only the stable component of HbAlc using the two most commonly used HPLC analyzers in our country. We found that a two-point calibration using lyophilized hemoglobin at lower and higher ranges was effective in matching up results of HbA1c measurement. This finding was concordant with a report by the Committee of the Japan Diabetes Society and other reports. Two methods of HbA1c immunoassay, one performed with the DCA 2000 automated analyzer and another performed using the Liquitech kit or a general automated analyzer, were evaluated and found to perform as well as HPLC analyzers in all respects except precision. The results derived from immunoassay were in good agreement with the calibrated results by HPLC, with (Liquitech) and without (DCA 2000) conversions.

  9. Does kindness matter? Self-compassion buffers the negative impact of diabetes-distress on HbA1c. (United States)

    Friis, A M; Johnson, M H; Cutfield, R G; Consedine, N S


    Higher self-compassion is associated with mental and physical health benefits in both healthy and chronically ill populations. The current study investigated the role of self-compassion in predicting depression, diabetes-specific distress and HbA1c in patients with diabetes. To assess the specific operationalization of negative emotionality that best predicted HbA1c and to test whether self-compassion would buffer HbA1c in patients with diabetes against the negative effects of distress. Patients with diabetes (n = 110) completed measures assessing trait self-compassion, depression and diabetes-distress. HbA1c results were obtained through medical records. As expected, diabetes-specific distress was a better predictor of HbA1c than depression; self-compassion moderated the relationship between distress and HbA1c such that higher distress predicted higher HbA1c at lower levels of self-compassion, but not at higher levels of self-compassion. In addition to further demonstrating the link between distress and metabolic outcomes, these findings suggest that self-compassion might buffer patients from the negative metabolic consequences of diabetes-distress. © 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.

  10. To establish trimester-specific reference ranges for glycated haemoglobin (HbA1c) in pregnancy

    LENUS (Irish Health Repository)

    O'Connor, CM


    Background and aims: Diabetes in Pregnancy imposes additional risks to both mother and infant. These poor outcomes are considered to be primarily related to glycaemic control which is monitored longitudinally through pregnancy by means of HbA1c. The correlation between HbA1c levels with clinical outcomes emphasises the need to measure HbA1c accurately, precisely and for data interpretation comparison to appropriately defined reference intervals. From July 1st 2010, the HbA1c assay in Irish laboratories became fully metrologically traceable to the IFCC standard, permitting HbA1c to be reported in IFCC units (mmol\\/mol) and derived DCCT\\/NGSP units (%) using the IFCC-DCCT\\/NGSP master equation (DCCT = Diabetes Control and Complications Trial, NGSP = National Glycohemoglobin standardisation program). The aim of this project is to establish trimester-specific reference ranges in pregnancy for IFCC standardised HbA1c in non-diabetic Caucasian women. This will allow us to define the goal for HbA1c during pregnancy complicated by diabetes.\\r\

  11. The role of HbA1c determination in detecting unknown glucose disturbances in ischemic stroke. (United States)

    Roquer, Jaume; Rodríguez-Campello, Ana; Cuadrado-Godia, Elisa; Giralt-Steinhauer, Eva; Jiménez-Conde, Jordi; Soriano, Carol; Ois, Angel


    To evaluate the usefulness of hemoglobin A1c (HbA1c) determinations during the acute ischemic stroke (IS) to identify undiagnosed glucose disturbances in a prospective series of patients with first-ever IS. Retrospective analysis of a prospective series of first-ever IS patients. Patients with previous diagnosis of diabetes mellitus (DM) were excluded from the study. Patients were classified as non-DM (HbA1cglucose> = 126 mg/dL), prediabetes (HbA1c from 5.7% to 6.4%), and new suspected DM (HbA1c> = 6.5% independently of current blood glucose). Medical charts from hospital discharge to July 2014 of all suspected DM patients were reviewed to confirm the DM diagnosis. The initial cohort included 1283 patients, of which 393 were excluded because of previous DM diagnosis and 136 because HbA1c during acute stroke phase was not available. No demographic differences were observed between patients with and without HbA1c determinations. The final cohort was composed of 754 patients with first-ever IS and unknown DM history. HbA1c determination suggested new DM in 87 cases (11.5%) and detected 273 patients with prediabetes (36.2%). New DM cases were identified in all etiological stroke subtypes. After discharge, DM diagnosis was confirmed in 80.2% of patients with available follow-up. HbA1c determination detected both undiagnosed DM and prediabetes in IS patients without taking into account the blood glucose values during admission, and independently of etiological stroke subtype. HbA1c determination should be included in the systematic screening of all IS patients.

  12. Benchmarking by HbA1c in a national diabetes quality register--does measurement bias matter? (United States)

    Carlsen, Siri; Thue, Geir; Cooper, John Graham; Røraas, Thomas; Gøransson, Lasse Gunnar; Løvaas, Karianne; Sandberg, Sverre


    Bias in HbA1c measurement could give a wrong impression of the standard of care when benchmarking diabetes care. The aim of this study was to evaluate how measurement bias in HbA1c results may influence the benchmarking process performed by a national diabetes register. Using data from 2012 from the Norwegian Diabetes Register for Adults, we included HbA1c results from 3584 patients with type 1 diabetes attending 13 hospital clinics, and 1366 patients with type 2 diabetes attending 18 GP offices. Correction factors for HbA1c were obtained by comparing the results of the hospital laboratories'/GP offices' external quality assurance scheme with the target value from a reference method. Compared with the uncorrected yearly median HbA1c values for hospital clinics and GP offices, EQA corrected HbA1c values were within ±0.2% (2 mmol/mol) for all but one hospital clinic whose value was reduced by 0.4% (4 mmol/mol). Three hospital clinics reduced the proportion of patients with poor glycemic control, one by 9% and two by 4%. For most participants in our study, correcting for measurement bias had little effect on the yearly median HbA1c value or the percentage of patients achieving glycemic goals. However, at three hospital clinics correcting for measurement bias had an important effect on HbA1c benchmarking results especially with regard to percentages of patients achieving glycemic targets. The analytical quality of HbA1c should be taken into account when comparing benchmarking results.

  13. Aging and ABO blood type influence von Willebrand factor and factor VIII levels through interrelated mechanisms. (United States)

    Albánez, S; Ogiwara, K; Michels, A; Hopman, W; Grabell, J; James, P; Lillicrap, D


    Essentials von Willebrand factor (VWF) and factor VIII (FVIII) levels are modulated by age and ABO status. The effect of aging and ABO blood type on VWF and FVIII was assessed in 207 normal individuals. Aging and ABO blood type showed combined and bidirectional influences on VWF and FVIII levels. Aging and ABO blood type influence VWF levels through both secretion and clearance mechanisms. Background The effect of aging and ABO blood type on plasma levels of von Willebrand factor (VWF) and factor VIII (FVIII) have been widely reported; however, a comprehensive analysis of their combined effect has not been performed and the mechanisms responsible for the age-related changes have not been determined. Objectives To assess the influence of aging and ABO blood type on VWF and FVIII levels, and to evaluate the contribution of VWF secretion and clearance to the age-related changes. Methods A cross-sectional observational study was performed in a cohort of 207 normal individuals, whose levels of VWF, FVIII, VWF propeptide (VWFpp), VWFpp/VWF:Ag ratio and blood type A antigen content on VWF (A-VWF) were quantified. Results Aging and ABO blood type exerted interrelated effects on VWF and FVIII plasma levels, because the age-related increase in both proteins was significantly higher in type non-O individuals (β = 0.011 vs. 0.005). This increase with age in non-O subjects drove the differences between blood types in VWF levels, as the mean difference increased from 0.13 U/mL in the young to 0.57 U/mL in the old. Moreover, A-VWF was associated with both VWF antigen (β = 0.29; 95% confidence interval [CI], 0.09, 0.50) and VWF clearance (β = -0.15; 95% CI, -0.25, -0.06). We also documented an effect of ABO blood type on VWF secretion with aging, as old individuals with blood type non-O showed higher levels of VWFpp (mean difference 0.29 U/mL). Conclusions Aging and ABO blood type have an interrelated effect on VWF and FVIII levels, where the effect of one is significantly

  14. Potential role of a new PEGylated recombinant factor VIII for hemophilia A

    Directory of Open Access Journals (Sweden)

    Wynn TT


    Full Text Available Tung Thanh Wynn,1 Burak Gumuscu,2,3 1Department of Pediatrics, Division of Pediatric Hematology/Oncology, University of Florida, Gainesville, FL, 2Pediatric Hematology-Oncology, Bon Secours Health System, St. Mary’s Hospital, Richmond, VA, 3Department of Pediatrics, Division of Pediatric Hematology/Oncology, University of Virginia, Charlottesville, VA, USA Abstract: Hemophilia A, a deficiency in the activity of coagulation factor (F VIII, is an X-linked bleeding disorder with an approximate incidence of one in 5,000 male infants. Bleeding-related complications often result in greater severity of disease, poor quality of life, surgical interventions for severe joint destruction, and shortened life span. With the availability of plasma-derived and recombinant FVIII products, the benefits of primary prophylaxis were demonstrated and is now the standard of care for patients with severe factor deficiencies. Current hemophilia research is focusing on the creation of new factor replacement therapies with longer half-lives; accessing alternative mechanisms to achieve desired hemostasis and enhance bypassing ­activity; and limiting the immunogenicity of the protein. PEGylation involves the covalent attachment of polyethylene glycol (PEG to a protein, peptide, or a small molecule drug. PEG effectively increases the molecular weight and size of the protein by creating a hydrophilic cloud around the molecule. This molecular change may reduce susceptibility of the molecule to proteolytic activity and degradation. It is also believed that PEGylation changes the surface charge of the protein that ultimately interferes with some receptor-mediated clearance processes. The half-life of PEGylated factor is more prolonged when compared to non-PEGylated full-length recombinant FVIII. The dawn of a new era in the care of hemophilia patients is upon us with the release of recombinant FVIII products with extended half-lives, and products with even more extended half


    Directory of Open Access Journals (Sweden)

    Ahmad Badawi


    Full Text Available Berpikir aljabar merupakan representasi dari aktivitas maupun kemampuan dalam mempelajari aljabar sekolah. Tujuan penelitian ini adalah untuk mengetahui kemampuan berpikir aljabar siswa SMP Kelas VIII. Metode penelitian yang digunakan adalah dengan pendekatan deskriptif kualitatif. Penelitian ini dilakukan dengan memberikan tes kemampuan berpikir aljabar pada siswa. Selanjutnya berdasarkan hasil tes, siswa dikelompokkan berdasarkan kemampuan berpikir aljabar mereka yang terdiri dari kelompok tingkat tinggi, kelompok tingkat sedang, dan kelompok tingkat rendah. Dari masing-masing kelompok tersebut dipilih dua subjek sebagai perwakilan untuk diwawancara lebih lanjut terkait kemampuan berpikir aljabar mereka. Hasil analisis dari penelitian ini menunjukkan bahwa kemampuan generasional, transformasional, dan level-meta global sudah terlihat pada sebagian siswa kelas VIII. Siswa yang termasuk dalam kelompok tingkat tinggi mempunyai kemampuan generasional, transformasional, dan level-meta global yang cenderung tinggi. Sedangkan siswa dalam kelompok rendah mempunyai kemampuan transformasional yang cenderung rendah, kemampuan generasional yang rendah sampai sedang, dan kemampuan level-meta global yang rendah sampai sedang.   Algebraic thinking is a representation of activities and abilities to learn school algebraic. The aim of this research was to determine the ability of eighth grade junior high school students in algebraic thinking. The method used in this research was the qualitative descriptive approach. This research was conducted with giving a test of algebraic thinking skills to the students. Furthermore, based on test results, students are grouped according to their algebraic thinking skills which consists of a high­level group, moderate­level group and low­level group. From each group, two subjects were selected to be interviewed more related their algebraic thinking skills, as a representative for their each group. Analytical results from


    Directory of Open Access Journals (Sweden)

    Apri Dwi Astuti


    Full Text Available Kemandirian belajar membantu siswa untuk bertanggung jawab dan menumbuhkan kesadaran belajar. Penggunaan uang saku menumbuhkan jiwa mandiri, jujur dan komitmen. Adapun hasil observasi awal menunjukkan masih ada siswa kels VII dan VIII SMP Semesta untuk kompetensi dasar ekonomi dibawah KKM. Tujuan penelitian ini untuk mengetahui pengaruh kemandirian belajar dn penggunaan uang saku terhadap prestasi belajar kompetensi dasar ekonomi kelas VII dan VIII SMP Semesta. Populasi penelitian ini adalah semua siswa kelas VII dan VIII SMP Semesta Boarding School Semarang. Variabel penelitian ini adalah kemandirian belajar dan penggunaan uang saku sebagai variabel bebas, sedangkan untuk� variabel terikat adalah prestasi belajar kompetensi dasar ekonomi. Data diambil dengan metode wawancara, kuesioner dan dokumentasi guru. Analisis data menggunakan analisis regresi linear berganda.Berdasarkan penelitian secara simultan menunjukkan adanya pengaruh antara kemandirian belajar dan penggunaan uang saku terhadap prestasi belajar kompetensi dasar ekonomi sebesar 51,3%. Secara parsial, pengaruh kemandirian belajar terhadap prestasi belajar kompetensi dasar ekonomi sebesar 66,2% dan pengaruh penggunaan uang saku terhadap prestasi belajar kompetensi dasar ekonomi sebesar 62,5%.Berdasarkan hasil penelitian diatas disimpulkan bahwa kemandirian belajar dan penggunaan uang saku berpengaruh positif baik secara simultan maupun parsial terhadap prestasi belajar kompetensi dasar ekonomi kelas VII dan VIII SMP Semesta Boarding school semarang tahun pelajaran 2011/2012. Saran yang berkaitan dengan penelitian ini yaitu : 1 Sekolah disarankan untuk memberikan batasan siswa pulang ke rumah agar dapat membantu siswa beradaptasi dengan cepat dan mudah tinggal di asrama. 2 Orang tua disarankan untuk memberikan uang saku yang disesuaikan dengan kebutuhan siswa. 3 Siswa disarankan untuk meningkatkan kemandirian dalam aspek belajar terutama bagi mata pelajaran yang masih kurang dari

  17. Recombinant B domain deleted porcine factor VIII for the treatment of bleeding episodes in adults with acquired hemophilia A. (United States)

    Gomperts, Edward


    Hemophilia A is an inherited deficiency of clotting factor VIII (FVIII) often complicated by inhibitor development (CHAWI) in which neutralizing antibodies block the therapeutic benefit of replacement therapy. Inhibitors to FVIII can also be seen in an auto-immune disease known as acquired hemophilia A (AHA). 'Bypassing' therapies have been shown to provide hemostasis but dosing must be done empirically because current assays cannot measure objective markers of treatment efficacy and safety. A recombinant porcine sequence factor VIII (r-pFVIII) has been developed for the management of AHA. Preclinical, Phase I and Phase II clinical research studies in CHAWI subjects showed therapeutic potential and safety of this agent. A Phase II/III study in AHA with serious bleeding episodes shows a positive response in all subjects after administration. Based on current preclinical and clinical trial data, r-pFVIII should become the first line of treatment in the management of hemorrhage in patients with AHA.

  18. [Detection of hemophilia A carriers by PCR analysis of hind III polymorphism in the factor VIII gene]. (United States)

    Wu, S; Li, Y; Cui, H; Xie, Y; Zheng, J; Pan, X; Zhang, H; Zhao, R; Zhang, Q


    To explore a scheme of using PCR analysis in the detection of carriers of Hind III polymorphism of factor VIII gene of hemophilia A. Implicating intron 19 of the factor VIII gene of 6 patients with the hemophilia A and 207 unrelated X-chromosomes were amplified by PCR and were analysed by means of Amp-RFLPs of Hind III. The incidence of the polymorphic Hind III sites in the given population was found to be 0.29. The frequence of the Hind III heterozygotes in women calculated according to Hardy-Weinberg equation was 0.41, which proved to be informative enough for carrier detection and prenatal diagnosis of hemophilia A. 2 out of 6 families (33%)examined in this study were informative. The new scheme proved to be effective for hemophilia A carrier detection and prenatal diagnosis.

  19. Comparative profiling of HLA-DR and HLA-DQ associated factor VIII peptides presented by monocyte-derived dendritic cells. (United States)

    Peyron, Ivan; Hartholt, Robin B; Pedró-Cos, Laura; van Alphen, Floris; Ten Brinke, Anja; Lardy, Neubury; Meijer, Sander; Voorberg, Jan


    The development of anti-factor VIII antibodies represents a major complication in the treatment of patients with hemophilia A. Generation of high affinity anti-factor VIII antibodies is dependent on help provided by CD4+ T cells that recognize factor VIII-derived peptides presented on class II major histocompatibility complex on the surface of antigen presenting cells. In order to identify the immune-dominant epitopes that can be presented to CD4+ T cells, we previously developed a mass-spectrometry based method to identify factor VIII derived peptides that are presented on human leucocyte antigen (HLA)-DR. In the present work, we compared the repertoire of FVIII-derived peptide presented on HLA-DR and HLA-DQ. Monocyte-derived dendritic cells from 9 HLA-typed healthy donors were pulsed with recombinant factor VIII. HLA-DR and HLA-DQ molecules were purified using monoclonal antibodies. Our data show that HLA-DQ and HLA-DR present a similar repertoire of factor VIII-derived peptides. However, the number of peptides associated with HLA-DQ was lower when compared to HLA-DR. We also identified a peptide, within the acidic a3 domains of factor VIII that is presented with higher frequency on HLA-DQ. Interestingly, this peptide was found to have a higher predicted affinity for HLA-DQ when compared to HLA-DR. Taken together, our data suggest that HLA-DQ participates in the presentation of factor VIII peptides, thereby contributing to the development of inhibitory antibodies in a proportion of patients with severe hemophilia A. Copyright © 2017, Ferrata Storti Foundation.

  20. HbA1c, systolic blood pressure variability and diabetic retinopathy in Asian type 2 diabetics. (United States)

    Foo, Valencia; Quah, Joanne; Cheung, Gemmy; Tan, Ngiap Chun; Ma Zar, Kyi Lin; Chan, Choi Mun; Lamoureux, Ecosse; Tien Yin, Wong; Tan, Gavin; Sabanayagam, Charumathi


    The aim of the present study was to examine the association between variability in HbA1c or systolic blood pressure (SBP) and diabetes-specific moderate retinopathy in Asians with type 2 diabetes (T2D). A retrospective study was conducted of 172 cases of moderate diabetic retinopathy (DR) cases and 226 controls without DR, matched for age, sex, and ethnicity. Serial HbA1c and SBP (range 3-6 readings) over the 2 years prior to photographic screening of DR were collected. Intrapersonal mean and SD values for HbA1c (iM-HbA1c and iSD-HbA1c) and SBP (iM-SBP and iSD-SBP) were derived. Moderate DR was assessed from digital retinal photographs and defined as levels >43 using the Early Treatment Diabetic Retinopathy Study scale. Cases of moderate DR had higher iM-HbA1c (8.2 % vs 7.3 %; P = 0.001), iSD-HbA1c (1.22 vs 0.64; P = 0.001), iM-SBP (136.8 vs 129.6 mmHg; P = 0.001) and iSD-SBP (13.3 vs 11.1; P = 0.002) than controls. In the multivariate regression model adjusted for age, gender, ethnicity, duration of diabetes, SBP, and HbA1c, iM-HbA1c and iM-SBP were significantly associated with moderate DR (odds ratio [OR] 1.80, 95 % confidence interval [CI] 1.37-2.36; and OR 1.03, 95 % CI 1.01-1.05, respectively). Neither iSD-HbA1c nor iSD-SBP were associated with moderate DR. When stratified by HbA1c Asian patients with T2D, both higher mean HbA1c levels and SBP, but not their variability, were associated with moderate DR. Among those with good glycemic control, wider variability of SBP is associated with moderate DR. © 2016 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

  1. Diabetes mellitus: The long way of standardization of HbA1c to the level of highest metrological order

    Directory of Open Access Journals (Sweden)

    Kaiser, Patricia


    Full Text Available Glycated haemoglobin (HbA1c measurements are used in clinical studies and for the management of diabetic patients. Various efforts were made to standardize the HbA1c measurements with consensus standards and standards based on a reference measurement procedure with external calibration. According to ISO 17511 a standard should meet highest accuracy possible, have a defined uncertainty of measurement and the calibration should be traceable to SI units. For HbA1c this has been realized using a LC-ID-MS procedure based on the existing reference measurement procedure.

  2. Development of Integrated Natural Science Teaching Materials Webbed Type with Applying Discourse Analysis on Students Grade VIII in Physics Class (United States)

    Sukariasih, Luh


    This study aims to produce teaching materials integrated natural science (IPA) webbed type of handout types are eligible for use in integrated science teaching. This type of research IS a kind of research and development / Research and Development (R & D) with reference to the 4D development model that is (define, design, develop, and disseminate). Data analysis techniques used to process data from the results of the assessment by the validator expert, and the results of the assessment by teachers and learners while testing is limited (12 students of class VIII SMPN 10 Kendari) using quantitative descriptive data analysis techniques disclosed in the distribution of scores on the scale of five categories grading scale that has been determined. The results of due diligence material gain votes validator material in the category of “very good” and “good”, of the data generated in the feasibility test presentation obtained the category of “good” and “excellent”, from the data generated in the feasibility of graphic test obtained the category of “very good “and” good “, as well as of the data generated in the test the feasibility of using words and language obtained the category of“very good “and” good “, so with qualifications gained the teaching materials IPA integrated type webbed by applying discourse analysis on the theme of energy and food for Junior High School (SMP) grade VIII suitable as teaching materials. In limited testing, data generated in response to a science teacher at SMPN 10 Kendari to product instructional materials as “excellent”, and from the data generated while testing is limited by the 12 students of class VIII SMPN 10 Kendari are more students who score indicates category “very good”, so that the qualification obtained by the natural science (IPA) teaching material integrated type webbed by applying discourse analysis on the theme of energy and food for SMP / class VIII fit for use as teaching material.

  3. Pengembangan Materi Luas Permukaan Dan Volum Limas Yang Sesuai Dengan Karakteristik Pmri Di Kelas VIII SMP Negeri 4 Palembang


    Hariyati, Hariyati; Indaryanti, Indaryanti; Zulkardi, Zulkardi


    Penelitian ini bertujuan mengembangkan materi luas permukaan dan volum limas dengan pendekatan PMRI. Subjek dalam penelitian ini adalah siswa kelas VIII SMP Negeri 4 Palembang. Dalam mengembangkan materi terdapat proses evaluasi formatif dan uji coba terhadap materi, yaitu expert review, one-to-one evaluation, small group, dan field test. Dari tiga tahap pertama, materi dinyatakan valid. Kemudian materi diujicobakan di lapangan (field test). Dari hasil uji coba diperoleh simpulan yaitu mengha...


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    Nuzul Andri Permana


    ___________________________________________________________________ Availability of practical tools in learning of science subject is needed to achieve the learning objectives. Based on observations in Junior High School 10 Semarang, practicum low intensity because of practical tools ara not available that support learning activities. The intensity of practicum is low, it make critical thinking skills of students is low. Critical thinking skills to be one of the variables that influence of understanding concept of learners. Availability of practicum tools that incomplete requires teachers to achieve the learning objectives by using media that can support learners to be able to do practicum virtually. Media that can support to do practicum virtually is a virtual laboratory. This study aims to determine the influence of virtual laboratory based flash animation againts understanding concepts and critical thinking skills of students in grade VIII SMP in optical theme. The population used in this study were all students of grade VIII Junior High School 10 Semarang academic year 2015/2016. Sampling technique used is purposive sampling and obtained VIII C as the experimental class and VIII F as the control class. The design of study is nonequivalent control group design. The results showed that the correlation value of understanding concept of students is 0.660 which shows in the strong category and correlation analysis of students' critical thinking skills of 0,729 based on observational data and 0.69 based on the posttest data that shows in the strong category. The influence of the use of virtual laboratory-based flash animation againts understanding concept of students is 43.53%, whereas the influence the use of virtual laboratory based flash animation againts the critical thinking skills of students is 53.14% based on observational data and 47.06% based on the posttest data. The conclusion is there are infuence of virtual laboratory based flash animation againts

  5. Neurotology findings in patients with diagnosis of vascular loop of cranial nerves VIII in magnetic resonance imaging

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    Grocoske, Francisco Luiz Busato

    Full Text Available Introduction: The vascular compression by redundant vessels under the VIII cranial nerves has been studied since the 80's, and many authors proposed correlations between the compression and the otoneurological findings (vertigo, tinnitus, hypoacusis, audiometry and electrophysiological findings. Objective: Analyze and correlate the different signs and otoneurological symptoms, the audiological findings and its incidence over individuals with Vascular Loop (VL diagnosis of VIII cranial nerves by magnetic resonance imaging (MRI. Method: Retrospective study through the analysis of medical records of 47 patients attended in the otoneurology clinic of Clinical Hospital of UFPR. All the patients have MRI exams with compatible pictures of VL of the VIII cranial nerves. Results: The tinnitus was the most frequent symptom, in 83% of the patients, followed by hypoacusis (60% and vertigo (36%. The audiometry presented alterations in 89%, the brainstem evoked auditory potential in 33% and the vecto-electronystagmography in 17% of the patients. Was not found statistically significant relation between the buzz or hypoacusis, and the presence of VL in MRI. Only 36% of patients had complaints of vertigo, the main symptom described in theory of vascular compression of the VIII pair of nerve. As in the audiometry and in brainstem evoked auditory potential was not found a statistically significant relation between the exam and the presence of the VL in the RMI. Conclusion: The results show independence between the findings of the RMI, clinical picture and audiological results (p>0,05 suggesting that there are no exclusive and direct relation between the diagnosis of vascular loop in the MRI and the clinical picture matching.

  6. Pengaruh Model Pembelajaran Berbasis Masalah terhadap Prestasi Belajar Matematika dan Keterampilan Berpikir Kritis Siswa Kelas VIII SMP Negeri 2 Abang




    Tujuan penelitian ini adalah untuk mendeskripsikan perbedaan prestasi belajar matematika dan keterampilan berpikir kritis antara siswa yang belajar dengan menerapkan model pembelajaran berbasis masalah dan siswa yang belajar dengan menerapkan model pembelajaran konvensional. Penelitian ini merupakan penelitian quasi experiment dengan pretest-posttest non-equivalent control group design. Sampel penelitian adalah dua kelas VIII di SMP Negeri 2 Abang tahun pelajaran 2015/2016 yang ditentukan den...

  7. MX Siting Investigation. Geotechnical Evaluation. Volume VIII. Nevada - Utah Verification Studies, FY 79. Geotechnical Data Big Smoky CDP, Nevada. (United States)


    Angular - particles have sharp edges and relatively plane sides with unpolished surfaces. wfl . AT#UNL, EWE. FN-TR-27-VIII 6-5 Subangular - particles... GEM ~GIC UNIT My ’All .’j GP T-3 C-33 St FACE ELEV TION: 492j * 1500m) SM jSIRFICIAL GE LOGIC UNIT: AMy A3 SW-SM F -6 C-34 SURFACE ELEVATION: 4938

  8. A fully liquid DTaP-IPV-HB-PRP-T hexavalent vaccine for primary and booster vaccination of healthy Turkish infants and toddlers (United States)

    Ceyhan, Mehmet; Yıldırım, İnci; Tezer, Hasan; Devrim, İlker; Feroldi, Emmanuel


    Background/aim: Immunogenicity and safety of a primary series of a fully liquid, hexavalent DTaP-IPV-HB-PRP-T vaccine given at 2, 3, and 4 months of age compared to licensed comparators and a DTaP-IPV-HB-PRP-T booster at 15?18 months were evaluated. Materials and methods: This was a Phase III, randomized, open-label trial. Primary series (no hepatitis B [HB] at birth) of DTaP-IPV-HB-PRP-T (N = 155) (group 1) or licensed control vaccines (DTaP-IPV//PRP-T and standalone HB: N = 155) (group 2) and DTaP-IPV-HB-PRP-T booster were administered. Noninferiority was evaluated 1 month postprimary series for anti-HB seroprotection (SP). All other analyses were descriptive. Safety was assessed from parental reports. Results: Postprimary series noninferiority of anti-HB ≥ 10 mIU/mL was demonstrated for the DTaP-IPV-HB-PRP-T vaccine (94.0%) compared to the licensed control (96.1%). Postprimary series primary SP and seroconversion (SC) rates were high and similar for both groups. Antibody persistence (prebooster) was high for each antigen and similar between groups except for HB, which was lower for DTaP-IPV-HB-PRP-T than for standalone HB. For each antigen except HB, DTaP-IPV-HB-PRP-T booster responses were high and similar in each group. Safety was good for primary and booster series and similar between groups. Conclusion: The DTaP-IPV-HB-PRP-T vaccine is immunogenic and safe when administered in a challenging primary series schedule without HB vaccination at birth.

  9. Capsicum annuum homeobox 1 (CaHB1) is a nuclear factor that has roles in plant development, salt tolerance, and pathogen defense

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Sang-Keun; Yoon, Joonseon [Department of Plant Science, College of Agriculture and Life Sciences, Seoul National University, Seou1 151-742 (Korea, Republic of); Choi, Gyung Ja [Screening Division, Korea Research Institute of Chemical Technology, Daejeon 305-600 (Korea, Republic of); Jang, Hyun A; Kwon, Suk-Yoon [Korea Research Institute of Bioscience and Biotechnology, Yusung, Daejeon 305-600 (Korea, Republic of); Choi, Doil, E-mail: [Department of Plant Science, College of Agriculture and Life Sciences, Seoul National University, Seou1 151-742 (Korea, Republic of)


    Highlights: •The CaHB1 is a nuclear factor, belonging to HD-Zip proteins. •SA and ET, as signal molecules, modulate CaHB1-mediated responses. •Overexpression of CaHB1 in tomato resulted in a thicker cell wall. •CaHB1-transgenic tomato confers resistance to Phytophthora infestans. •CaHB1 enhanced tolerance to saline stress in tomato. -- Abstract: Homeodomain-leucine zipper (HD-Zip) family proteins are unique to plants, but little is known about their role in defense responses. CaHB1 is a nuclear factor in peppers, belonging to subfamily II of HD-Zip proteins. Here, we determined the role of CaHB1 in the defense response. CaHB1 expression was induced when pepper plants were challenged with Phytophthora capsici, a plant pathogen to which peppers are susceptible, or environmental stresses such as drought and salt stimuli. CaHB1 was also highly expressed in pepper leaves following application of SA, whereas ethephon and MeJA had a moderate effect. To further investigate the function of CaHB1 in plants, we performed gain-of-function study by overexpression of CaHB1 in tomato. CaHB1-transgenic tomatoes showed significant growth enhancement including increased leaf thickness and enlarged cell size (1.8-fold larger than control plants). Microscopic analysis revealed that leaves from CaHB1-transgenic plants had thicker cell walls and cuticle layers than those from controls. Moreover, CaHB1-transgenic plants displayed enhanced resistance against Phytophthora infestans and increased tolerance to salt stress. Additionally, RT-PCR analysis of CaHB1-transgenic tomatoes revealed constitutive up-regulation of multiple genes involved in plant defense and osmotic stress. Therefore, our findings suggest roles for CaHB1 in development, salt stress, and pathogen defense.


    Directory of Open Access Journals (Sweden)

    Muhammad Taufiq


    Full Text Available The purpose of this result the study learning of hockey games through the 4 Small Wicket Game in Grade VIII 3 students of Smp Muhammadiyah 4 Semarang. In this case the right is 4 semarang. research method. In practice consists of two cycles. Based on the results of the research, it showed the percentage of passing students study result in the first cycle, students who got pass score are 58.33% (21 students and who did not pass are 41.66% (15 students. In the second cycle students who got pass score are 88.88% (34 students and students who did not pass are 11.11% (4 students. It indicates an increase completeness of student study result is 30.55%.Based on the research’s result, it can be concluded that the use of 4 Small Wicket Game in Grade VIII 3 students is right to improve the study result of grade VIII 3 students of SMP Muhammadiyah 4 Semarang in learning hockey.

  11. Partial correction of a severe molecular defect in hemophilia A, because of errors during expression of the factor VIII gene

    Energy Technology Data Exchange (ETDEWEB)

    Young, M.; Antonarakis, S.E. [Univ. of Geneva (Switzerland); Inaba, Hiroshi [Tokyo Medical College (Japan)] [and others


    Although the molecular defect in patients in a Japanese family with mild to moderately severe hemophilia A was a deletion of a single nucleotide T within an A{sub 8}TA{sub 2} sequence of exon 14 of the factor VIII gene, the severity of the clinical phenotype did not correspond to that expected of a frameshift mutation. A small amount of functional factor VIII protein was detected in the patient`s plasma. Analysis of DNA and RNA molecules from normal and affected individuals and in vitro transcription/translation suggested a partial correction of the molecular defect, because of the following: (i) DNA replication/RNA transcription errors resulting in restoration of the reading frame and/or (ii) {open_quotes}ribosomal frameshifting{close_quotes} resulting in the production of normal factor VIII polypeptide and, thus, in a milder than expected hemophilia A. All of these mechanisms probably were promoted by the longer run of adenines, A{sub 10} instead of A{sub 8}TA{sub 2}, after the delT. Errors in the complex steps of gene expression therefore may partially correct a severe frameshift defect and ameliorate an expected severe phenotype. 36 refs., 6 figs.

  12. Nota sobre antígeno relacionado à hepatite (HB Ag e anticorpo (HB Ab em população do território Federal do Amapá

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    Hermann G. Schatzmayr


    Full Text Available 53 amostras de soro, provenientes de Ferreira Gomes, no Amapá, foram testados para antígeno HB Ag e anticorpo HB Ab, com uma positividade de 3,7% para HB Ag, sub-tipo D. Os autores acentuam a necessidade de inquéritos em populações brasileiras a fim de estabelecer os sub-tipos associados à hepatite.3,7% of 53 serum samples from healthy inhabitants of Ferreira Gomes, Amapá, were positive for HB Ag, subtype D. The authors síress the needs of surveys to deteet the prevalent types of antigens associated with viral hepatitis in different areas of Brazil.

  13. HbA(1c) in nondiabetic dutch infants aged 8-12 months - the GECKO-Drenthe birth cohort study

    NARCIS (Netherlands)

    Jansen, Hanneke; Huiting, Haika G.; Scholtens, Salome; Sauer, Pieter J. J.; Stolk, Ronald P.

    OBJECTIVE-An international committee of experts recommended using HbA(1c) for diagnostic testing for diabetes. Little is known about normal values of HbA(1c) in infants. The aim of this study is to describe the distribution of HbA(1c) in 8- to 12-month-old nondiabetic infants. RESEARCH DESIGN AND

  14. Functional mapping of the A2 domain from human factor VIII. (United States)

    Plantier, Jean-Luc; Saboulard, Didier; Pellequer, Jean-Luc; Négrier, Claude; Delcourt, Marc


    Coagulation factor VIII (FVIII) is a multidomain glycoprotein in which the FVIII A2 domain is a key structural element. We aimed at identifying residues within FVIII A2 domain that are crucial for the maintenance of the cofactor function. A high number (n=206) of mutants were generated by substituting original residues with alanine. The mutants were expressed in COS-1 cells and their antigen levels and procoagulant activities were measured. The residues were classified in three categories: those with a non-detrimental alteration of their activities (activity >50 % of control FVIII; n=98), those with a moderate alteration (15 %maintenance of the A2 domain structure. In contrast, residues resistant to mutations formed external loops without well- defined structures suggesting that these loops were not crucial for the process of factor X activation. This study provided a detailed map of the FVIII A2 domain between residues 371 and 649, identifying residues crucial for maintaining FVIII function and residues that can be mutated without jeopardising the coagulant activity.

  15. Characteristics of rabbit transgenic mammary gland expressing recombinant human factor VIII. (United States)

    Chrenek, P; Makarevich, A V; Pivko, J; Massanyi, P; Lukac, N


    The objective of this research was to compare (i) the content of milk protein and recombinant human factor VIII (rhFVIII) in the milk of transgenic and non-transgenic rabbit females at three lactations and (ii) histological structure, ultrastructural morphology and occurrence of apoptosis in rabbit transgenic and non-transgenic mammary gland during third lactation and involution. Significant differences (t(0.05)) in milk protein content were found between transgenic and non-transgenic at all three lactations. The percentage of apoptotic cells was significantly higher (t(0.01)) in non-transgenic ones compared with transgenic mammary gland tissues (6.5% versus 2.4%) taken at the involution stage. Morphometrical analysis of histological preparations at the involution stage detected a significantly higher (t(0.05)) relative volume of lumen in transgenic animals compared with non-transgenic ones (60.00 versus 46.51%). Ultrastructural morphology of the transgenic mammary gland epithelium at the involution stage revealed an increased relative volume of protein globules (t(0.05)); at the lactation stage, a significantly higher volume of mitochondria (13.8%) compared with the non-transgenic (9.8%) ones was observed. These results, although revealing differences in some parameters of ultrastructure and histology, indicate no harmful effect of the mouse whey acid protein-hFVIII transgene expression on the state of mammary gland of transgenic rabbit females.

  16. [Organoleptic and physicochemical characteristics of propolis in the Province Of Nuble, VIII Region-Chile]. (United States)

    Hernández, M S; Lazo, C S; Junod, J M; Arancibia, J M; Flores, R S; Valencia, A E; Valenzuela, E V


    Propolis ("bee-glue") is a gummy resinous substance elaborated by honey bees (Apis mellifera) from different types of plant resins. The chemical composition of propolis is very complex and variable as it depends on the botanical source and the environmental conditions prevailing at the location where the resin is collected by bees. The objective [corrected] of this study was to determine the propolis organoleptic and physicochemical properties of different types in the Province of Nuble (VIII Región, Chile). Samples were collected at different sites located in the Central Valley, ranging from the coast to the mountain skirts. Analyses included humidity, ashes, wax content, total phenolics content, total flavonoids, mechanical impurities, oxidation time, and solubility in ethanol. Results showed that propolis extracts from coastal sites are better quality than those collected at mountain skirts, and these in turn are better than propolis obtained from the Central Valley. All propolis analyzed in this study can be classified according to the Brazilian norm as high flavonoid content. The same homogeneity is observed in the amounts of total phenolics found in the samples. In general terms, properties of the propolis samples analyzed fulfill the quality requirements of the current international standards.


    Directory of Open Access Journals (Sweden)

    Dahler Dahler


    Full Text Available This research is based on the problem faced by the students such as: difficulty inunderstanding the generic structures of descriptive text and the difficulties in developingparagraph. The purpose of this research was to improve the students’ writing skill by usingNeuro Linguistics Programming (NLP strategy at VIII grade of SMPN 11 Mandau Duri. Theresearch design was Classroom Action Research (CAR consisted of two cycles. The datawere collected by using test, field note, observation sheet, and interview. Then, the datacollected were analyzed by using scoring rubric of writing descriptive text. The result showedthat students’ ability in writing descriptive text could be improved. It could be seen frombased score of students writing skill was 38 (failed improve to 51 (failed in cycle 1 to 70(Pass in cycle II. It was caused by some factors, those were the teacher gave motivation,created enjoyfull experience, comfortable class and used various media. In conclusion, theuse of NLP strategy has many beneficial.Keywords:Writing skill, Descriptive Text and NLP strategy.

  18. [Determinants of the elevated factor VIII activity in patients following venous thromboembolism]. (United States)

    Lech, Monika; Kościelniak, Barbara; Bryk, Agata; Undas, Anetta


    Activity of factor VIII (FVIII) increased above 150% of reference range predisposes to venous thromboembolism (VTE). The aim of this study was to identify predictors of increased FVIII activity in patients following VTE. 241 (38% men) patients presented due to objectively documented VTE episode at least 3 months ago were included in this study. FVIII activity was measured using a clotting assay on the analyzer BCS XP. Among 241 patients with VTE, activity of FVIII above 150% (FVIII ≥ 150%) was observed in 96 (40%). These patients were older (p = 0.035) and their concentrations of fibrinogen and C-reactive protein (CRP) were higher by 12% and 88% (p 200%) and this group was also older (p = 0.015), more patients in that group had obesity (p = 0.015), idiopathic VTE (p = 0.043), less of them had positive family history (p = 0.010) and they were characterized by fibrinogen and CRP increased by 28% (p 200% (p = 0.016). The activity of FVIII in patients after VTE episode is influenced by age, concentration of fibrinogen, bilirubin, hemoglobin, glucose, CRP and homocysteine. Our results suggest the role of environmental factors, mainly inflammatory response in maintaining elevated FVIII activity following VTE.


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    Rezky Ramadhona


    Full Text Available Penelitian ini bertujuan untuk mengetahui apakah motivasi dan hasil belajar belajar matematika siswa kelas VIII SMPN 1 Sawahlunto setelah menggunakan mind map dan musik klasik lebih baik dari sebelum menggunakan mind map dan musik klasik. Jenis penelitian ini adalah penelitian eksperimen dengan menggunakan dua model rancangan yaitu One Group Pretest Posttest Design untuk melihat dampak perlakuan terhadap motivasi belajar dan Randomized Control Group Only Design untuk melihat dampak perlakuan terhadap hasil belajar. Pengumpulan data dalam penelitian ini menggunakan angket dan tes akhir berupa soal essai. Data yang diperoleh dianalisis dengan menggunakan Uji-t. Hasil penelitian menunjukkan bahwa motivasi belajar matematika siswa cenderung meningkat. Jadi disimpulkan bahwa motivasi belajar matematika siswa setelah menggunakan mind map dan musik klasik lebih baik dari pada sebelum menggunakan mind map dan musik klasik. Dari hasil uji hipotesis untuk data hasil belajar pada selang kepercayaan α = 0,05 diperoleh P-value = 0,022. Jadi dapat disimpulkan bahwa hasil belajar matematika siswa yang menggunakan mind map dan musik klasik lebih baik dari hasil belajar matematika siswa yang tidak menggunakan mind map dan musik klasik. Kata Kunci: Mind Map, Musik Klasik DOI:

  20. Immunomodulation of transgene responses following naked DNA transfer of human factor VIII into hemophilia A mice. (United States)

    Miao, Carol H; Ye, Peiqing; Thompson, Arthur R; Rawlings, David J; Ochs, Hans D


    A robust humoral immune response against human factor VIII (hFVIII) following naked DNA transfer into immunocompetent hemophilia A mice completely inhibits circulating FVIII activity despite initial high-level hFVIII gene expression. To prevent this undesirable response, we compared transient immunomodulation strategies. Eight groups of mice (n = 4-9 per group) were treated with naked DNA transfer of pBS-HCRHPI-hFVIIIA simultaneously with immunosuppressive reagents that included cyclosporine A (CSA), rapamycin (RAP), mycophenylate mofetil (MMF), a combination of CSA and MMF, a combination of RAP and MMF, a monoclonal antibody against murine CD40 ligand (MR1), recombinant murine Ctla4Ig, and a combination of MR1 and Ctla4Ig. All animals except those receiving only CSA exhibited delayed or absent immune responses against hFVIII. The most effective immunosuppressive regimen, the combination of Ctla4Ig and MR1, prevented inhibitor formation in 8 of 9 animals; the ninth had transient low-titer antibodies. All 9 mice of this group produced persistent, therapeutic levels of hFVIII for more than 6 months. When challenged with the T-dependent antigen bacteriophage Phix174, tolerized mice exhibited normal primary and secondary antibody responses, suggesting that transient immunomodulation to disrupt B/T-cell interaction at the time of plasmid injection effectively promoted long-term immune tolerance specific for hFVIII.

  1. Optimisation of the Factor VIII yield in mammalian cell cultures by reducing the membrane bound fraction

    DEFF Research Database (Denmark)

    Kolind, Mille Petersen; Nørby, Peder Lisby; Berchtold, Martin Werner


    of active membrane bound rFVIII to the culture medium. Moreover, the attachment of rFVIII to cell membranes of un-transfected HEK293 cells was studied in the presence of compounds that competes for interactions between rFVIII and PS. Competitive assays between iodinated rFVIII (¹²5I-rFVIII) and annexin V......In vivo, clotting Factor VIII (FVIII) circulates in plasma bound to von Willebrand factor (vWF), and the vWF:FVIII complex prevents binding of FVIII to phosphatidylserine (PS). Activation of FVIII by thrombin releases FVIII from vWF, and subsequently FVIII binds to PS exposed on activated platelets...... of the production cells. Recently, we showed that as much as 90% of secreted rFVIII is bound to transiently transfected production cells during serum free conditions. In this study, we investigated the effect of including vWF in the serum free medium, and demonstrate that addition of vWF results in release...

  2. Eradication of neutralizing antibodies to factor VIII in canine hemophilia A after liver gene therapy. (United States)

    Finn, Jonathan D; Ozelo, Margareth C; Sabatino, Denise E; Franck, Helen W G; Merricks, Elizabeth P; Crudele, Julie M; Zhou, Shangzhen; Kazazian, Haig H; Lillicrap, David; Nichols, Timothy C; Arruda, Valder R


    Inhibitory antibodies to factor VIII (FVIII) are a major complication in the treatment of hemophilia A, affecting approximately 20% to 30% of patients. Current treatment for inhibitors is based on long-term, daily injections of large amounts of FVIII protein. Liver-directed gene therapy has been used to induce antigen-specific tolerance, but there are no data in hemophilic animals with pre-existing inhibitors. To determine whether sustained endogenous expression of FVIII could eradicate inhibitors, we injected adeno-associated viral vectors encoding canine FVIII (cFVIII) in 2 strains of inhibitor hemophilia A dogs. In 3 dogs, a transient increase in inhibitor titers (up to 7 Bethesda Units [BU]) at 2 weeks was followed by continuous decline to complete disappearance within 4-5 weeks. Subsequently, an increase in cFVIII levels (1.5%-8%), a shortening of clotting times, and a reduction (> 90%) of bleeding episodes were observed. Immune tolerance was confirmed by lack of antibody formation after repeated challenges with cFVIII protein and normal protein half-life. A fourth dog exhibited a strong early anamnestic response (216 BU), with slow decline to 0.8 BU and cFVIII antigen detection by 18 months after vector delivery. These data suggest that liver gene therapy has the potential to eradicate inhibitors and could improve the outcomes of hemophilia A patients.

  3. Lithium ionophore VIII as an extraordinarily effective receptor for the strontium cation: Experimental and theoretical study (United States)

    Makrlík, Emanuel; Novák, Vít; Vaňura, Petr; Bouř, Petr


    From extraction experiments and γ-activity measurements, the extraction constant corresponding to the equilibrium Sr2+(aq) + 2A-(aq) + 1(nb) ⇔ 1ṡSr2+(nb) + 2A-(nb) taking place in the two-phase water-nitrobenzene system (A- = picrate, 1 = lithium ionophore VIII; aq = aqueous phase, nb = nitrobenzene phase) was evaluated as log Kex (1ṡSr2+, 2A-) = 7.8 ± 0.1. Further, the extremely high stability constant of the 1ṡSr2+ complex in nitrobenzene saturated with water was calculated for a temperature of 25 °C: log βnb (1ṡSr2+) = 16.9 ± 0.1. Finally, by using DFT calculations, the most probable structure of the cationic complex species 1ṡSr2+ was derived. In the resulting complex, the "central" cation Sr2+ is bound by six very strong bond interactions to the corresponding six oxygen atoms of the parent ligand 1; the interaction energy of this complex was found to be -959.9 kJ/mol.

  4. Lithium ionophore VIII as an extraordinarily strong receptor for the trivalent europium cation (United States)

    Makrlík, Emanuel; Novák, Vít; Vaňura, Petr


    On the basis of extraction experiments and γ-activity measurements, the extraction constant corresponding to the equilibrium Eu3+(aq) + 3A-(aq) + 1(nb) ⇆ 1.Eu3+(nb) + 3A-(nb) occurring in the two-phase water-nitrobenzene system (A- = CF3SO-3; 1 = lithium ionophore VIII; aq = aqueous phase, nb = nitrobenzene phase) was determined as log Kex (1.Eu3+, 3A-) = 2.5 ± 0.1. Furthermore, the extremely high stability constant of the 1.Eu3+ complex in nitrobenzene saturated with water was calculated: log βnb (1.Eu3+) = 15.6 ± 0.1. Finally, by using DFT calculations, the most probable structure of the cationic complex species 1.Eu3+ was derived. In the resulting complex, the 'central' cation Eu3+ is bound by six very strong bond interactions to the corresponding six oxygen atoms of the parent ligand 1. It is evident that this exceptionally effective receptor 1 for the Eu3+ cation could be considered as a potential extraction agent for nuclear waste treatment.


    Directory of Open Access Journals (Sweden)

    A. Setyowati


    Full Text Available Tujuan dari penelitian ini adalah untuk mengetahui pengaruh implementasi pendekatan konflik kognitif dalam pembelajaran fisikapokok bahasan tekanan pada siswa kelas VIII terhadap kemampuan berpikir kritis, pemahaman konsep dan hasil belajar kognitifsiswa. Penelitian ini merupakan penelitian eksperimen. Setelah dilakukan pengambilan sampel secara random sampling,diperoleh kelas VIIIB sebagai kelas eksperimen dan kelas VIIIC sebagai kelas kontrol. Dari analisis uji rata-rata dua pihak atau uji tdiperoleh harga t tabel < t hitung yang berarti bahwa terdapat perbedaan yang signifikan terhadap rata-rata kemampuan berpikir kritis,pemahaman konsep dan hasil belajar kognitif kedua kelompok. Kesimpulan dari penelitian ini adalah implementasi pendekatankonflik kognitif pada pokok bahasan tekanan efektif digunakan dalam menumbuhkan kemampuan berpikir kritis, pemahamankonsep dan hasil belajar kognitif siswa kelas VIIISMP. This experiment research aims to examine the influence of cognitive conflict approach application to physics lesson with pressuretopic on critical thinking ability, concept understanding and cognitive learning achievement of the student. The random samplingused resulted class VIIIC as control group and VIIIB as experiment group. The t-test was performed to analyse the average ofcritical thinking ability, concept understanding and cognitive learning achievement of both groups. It was concluded thatimplementation of cognitive conflict approach to physics lesson with pressure topic can grow critical thinking ability, conceptunderstanding and cognitive learning achievement of the JHS student.Keyword: cognitive conflict approach, critical thinking ability, concept understanding, cognitive learning achievement

  6. Nattokinase decreases plasma levels of fibrinogen, factor VII, and factor VIII in human subjects. (United States)

    Hsia, Chien-Hsun; Shen, Ming-Ching; Lin, Jen-Shiou; Wen, Yao-Ke; Hwang, Kai-Lin; Cham, Thau-Ming; Yang, Nae-Cherng


    Nattokinase, a serine proteinase from Bacillus subtilis, is considered to be one of the most active functional ingredients found in natto. In this study, we hypothesized that nattokinase could reduce certain factors of blood clotting and lipids that are associated with an increase risk for cardiovascular disease (CVD). Thus, an open-label, self-controlled clinical trial was conducted on subjects of the following groups: healthy volunteers (Healthy Group), patients with cardiovascular risk factors (Cardiovascular Group), and patients undergoing dialysis (Dialysis Group). All subjects ingested 2 capsules of nattokinase (2000 fibrinolysis units per capsule) daily orally for 2 months. The laboratory measurements were performed on the screening visit and, subsequently, regularly after the initiation of the study. The intent-to-treat analysis was performed on all 45 enrolled subjects. By use of mixed model analysis, a significant time effect, but not group effect, was observed in the change from baseline of fibrinogen (P = .003), factor VII (P nattokinase. No significant changes of uric acid or notable adverse events were observed in any of the subjects. In summary, this study showed that oral administration of nattokinase could be considered as a CVD nutraceutical by decreasing plasma levels of fibrinogen, factor VII, and factor VIII.

  7. Influence of ABO type on global coagulation assay results: effect of coagulation factor VIII. (United States)

    Choi, Qute; Kim, Ji-Eun; Kim, Seon Young; Han, Kyou Sup; Kim, Hyun Kyung


    As ABO blood type influences the plasma level of coagulation factor VIII (FVIII), it likely also affects activated partial thromboplastin time (aPTT) and thrombin generation assay (TGA) values. Here, we aimed to investigate the effect of ABO type on the normal values of three global coagulation assays: prothrombin time (PT), aPTT, and TGA. PT, aPTT, TGA [1 or 5 pmol/L tissue factor (TF)], coagulation factors, anticoagulation factors, and ABO type were measured in 200 healthy adults. aPTT was significantly prolonged in those with type O compared with those with type non-O, whereas PT was not significantly different between those with type O and type non-O. The time to peak induced by 5 pmol/L TF was significantly prolonged, and the peak thrombin level was decreased in those with type O compared with those with type non-O. FVIII was a major contributor to the ABO-specific reference range of aPTT, 5 pmol/L TF-induced time to peak, and peak thrombin level. The reference ranges of aPTT and TGA (time to peak and peak thrombin level) differed by ABO type. FVIII level is considered a major contributor to ABO type-specific differences with respect to aPTT and TGA.

  8. Penggunaan Media Software GeoGebra untuk Meningkatkan Kemampuan Representasi Matematis Siswa SMP Kelas VIII

    Directory of Open Access Journals (Sweden)

    Marini Oktaria


    Full Text Available Rendahnya kemampuan representasi matematis siswa menjadi salah satu penyebab rendahnya prestasi belajar matematika siswa. Hal ini diperkuat dengan hasil laporan TIMSS dan PISA yang menunjukkan rendahnya kemampuan matematika siswa Indonesia. Untuk membantu siswa meningkatkan kemampuan representasi matematis digunakan suatu media pembelajaran matematika. Salah satu media pembelajaran matematika yang dapat merepresentasikan model matematika adalah software GeoGebra. Maka dari itu, penelitian ini bertujuan untuk mengetahui apakah software GeoGebra dapat meningkatkan kemampuan representasi matematis siswa pada materi SPLDV. Sampel dalam penelitian ini adalah siswa kelas VIII.2 SMP Islamic Village tahun ajaran 2015/2016 semester II sebanyak 29 orang dengan purposive sampling. Instrumen penelitian berupa tes uraian untuk mengukur kemaampuan representasi matematis. Metode dalam penelitian ini adalah metode kuantitatif jenis pra eksperimen dengan one group pretest-posttest design. Analisis data penelitian ini menggunakan uji non-parametrik Wilcoxon Signed Ranks Test. Hasil penelitian menunjukkan bahwa penggunaan media software GeoGebra dapat meningkatkan kemampuan representasi matematis siswa pada materi sistem persamaan linier dua variabel (SPLDV. Peningkatan yang diperoleh berada pada kategori sedang sebesar 0,651

  9. Allometry of Factor VIII and informed scaling of next generation therapeutic proteins (United States)

    Kosloski, Matthew P.; Pisal, Dipak S.; Mager, Donald E.; Balu-Iyer, Sathy V.


    Allometric scaling has been applied to the pharmacokinetics (PK) of factor VIII (FVIII), but published relationships are based on relatively small subsets of available data. Numerous next generation forms of FVIII are being developed (e.g. Fc fusion, PEGylated, and liposomal formulations) and traditional pharmacokinetic scaling of these products would not incorporate the wealth of existing knowledge for current FVIII therapy in humans. We conducted a meta-analysis and developed allometric relationships of FVIII from over 100 PK studies collected from literature. Normalized Wajima curves were used to relate mean FVIII profiles between species. An ‘informed scaling’ approach was derived for predicting first-in-human PK parameters and demonstrated with a case study for an Fc fusion FVIII. NCA values for FVIII PK were well described by the allometric equations CL=6.59·W0.85 and Vss=65.0·W0.97. A subset of studies characterized by two compartment modeling showed strong linearity in scaling of total clearance and central volume, but more variability in distributional clearance and peripheral volume. Wajima curves for FVIII superimposed across species and the disposition of Fc fusion FVIII in humans was well predicted by ‘informed scaling.’ This approach might be generally applicable for predicting human PK of next generational therapeutics. PMID:23620343

  10. Potential for cellular stress response to hepatic factor VIII expression from AAV vector

    Directory of Open Access Journals (Sweden)

    Irene Zolotukhin


    Full Text Available Hemophilia A and B are coagulation disorders resulting from the loss of functional coagulation factor VIII (FVIII or factor IX proteins, respectively. Gene therapy for hemophilia with adeno-associated virus vectors has shown efficacy in hemophilia B patients. Although hemophilia A patients are more prevalent, the development of therapeutic adeno-associated virus vectors has been impeded by the size of the F8 cDNA and impaired secretion of FVIII protein. Further, it has been reported that over-expression of the FVIII protein induces endoplasmic reticulum stress and activates the unfolded protein response pathway both in vitro and in hepatocytes in vivo, presumably due to retention of misfolded FVIII protein within the endoplasmic reticulum. Engineering of the F8 transgene, including removal of the B domain (BDD-FVIII and codon optimization, now allows for the generation of adeno-associated virus vectors capable of expressing therapeutic levels of FVIII. Here we sought to determine if the risks of inducing the unfolded protein response in murine hepatocytes extend to adeno-associated virus gene transfer. Although our data show a mild activation of unfolded protein response markers following F8 gene delivery at a certain vector dose in C57BL/6 mice, it was not augmented upon further elevated dosing, did not induce liver pathology or apoptosis, and did not impact FVIII immunogenicity.

  11. Point-of-care testing of HbA1c in diabetes care and preventable hospital admissions

    DEFF Research Database (Denmark)

    Kristensen, Troels; Rose Olsen, Kim

    Background: Point-of-care testing (POCT) of HbA1c may result in improved diabetic control, better patient outcomes and enhanced clinical efficiency with fewer patient visits and subsequent reductions in hospitalizations and costs. In 2008, the Danish regulators agreed to create a new tariff...... for the remuneration of POCT of HbA1c in primary care. Aim: The aim of this study is to assess whether there is an association between the use of POCT of HbA1c and preventable hospital admissions among diabetes patients in general practice. Method: We apply logistic regression analyses to examine whether......, socioeconomic covariates, municipality classifications and case mix measure in terms of the charlson index and costs of care in primary care and secondary care. Results: There was a significant link between POCT of HbA1c among diabetes patients in general practice and an ACSC-measure of preventable out...

  12. Lacking deoxygenation-linked interaction between cytoplasmic domain of band 3 and HbF from fetal red blood cells

    DEFF Research Database (Denmark)

    Weber, Roy E.


    Aim: Several of the red blood cell's metabolic and membrane functions display dependence on haemoglobin oxygenation. In adult human red cells, the increased glycolytic rate at low O2 tension results from binding of deoxygenated HbA at negatively charged, N-terminal, cytoplasmic domain...... of the membrane protein band 3, which liberates glycolytic enzymes from this site. This study aims to investigate the role of fetal HbF (that has lower anion-binding capacity than HbA) in fetal red cells (that are subjected to low O2 tensions), and to elucidate possible linkage (e.g. via the major red cell...... membrane organising centre, band 3) between the individual oxygenation-linked reactions encountered in red cells. Methods: The interaction between band 3 and Hb is analysed in terms of the effects, measured under different conditions, of a 10-mer peptide that corresponds to the N-terminus of human band 3...

  13. Detection of Hb E mutation (beta(26), GAG-AAG, Glu-Lys) using allelic discrimination analysis. (United States)

    Sangkitporn, S; Sangkitporn, S K; Sangnoi, A; Duangruang, S


    A method for detection of hemoglobin (Hb) E mutation was developed based on allelic discrimination analysis. Two probes labeled with different fluorescent reporter dyes were designed to specifically detect variation of a single nucleic acid polymorphism (SNP) site in the target template sequence. Polymerase chain reaction (PCR) products of normal allele and mutant allele were detected directly by analyzing fluorescent signal of each probe. This method was validated in term of accuracy (by comparing with sequence analysis) and reproducibility. The % CV between run precision was 5.16-8.86%. The narrow scatter of the results confirmed the reproducibility of the assay. This technique is a rapid, reliable and cost-effective method to differentiate Hb E homozygosity from beta(0)-thalassemia/Hb E in populations with a high frequency of beta-thalassemia and Hb E.

  14. Impact of Disease Management Programs on HbA1c Values in Type 2 Diabetes Patients in Germany. (United States)

    Kostev, Karel; Rockel, Timo; Jacob, Louis


    The aim was to analyze the impact of disease management programs on HbA1c values in type 2 diabetes mellitus (T2DM) patients in Germany. This study included 9017 patients followed in disease management programs (DMPs) who started an antihyperglycemic treatment upon inclusion in a DMP. Standard care (SC) patients were included after individual matching (1:1) to DMP cases based on age, gender, physician (diabetologist versus nondiabetologist care), HbA1c values at baseline, and index year. The main outcome was the share of patients with HbA1c <7.5% or 6.5% after at least 6 months and less than 12 months of therapy in DMP and SC groups. Multivariate logistic regression models were fitted with HbA1c level as a dependent variable and the potential predictor (DMP versus SC). The mean age was 64.3 years and 54.7% of the patients were men. The mean HbA1c level at baseline was equal to 8.7%. In diabetologist practices, 64.7% of DMP patients and 55.1% of SC patients had HbA1c levels <7.5%, while 23.4% of DMP patients and 16.9% of SC patients had HbA1c levels <6.5% ( P values < .001). By comparison, in general practices, 72.4% of DMP patients and 65.7% of SC patients had HbA1c levels <7.5%, while 29.0% of DMP patients and 25.4% of SC patients had HbA1c levels <6.5% ( P values < .001). DMPs increased the likelihood of HbA1c levels lower than 7.5% or 6.5% after 6 months of therapy in both diabetologist and general care practices. The present study indicates that the enrollment of T2DM patients in DMPs has a positive impact on HbA1c values in Germany.

  15. Implications of iron deficiency/anemia on the classification of diabetes using HbA1c. (United States)

    Attard, S M; Herring, A H; Wang, H; Howard, A-G; Thompson, A L; Adair, L S; Mayer-Davis, E J; Gordon-Larsen, P


    Nonglycemic factors like iron deficiency (ID) or anemia may interfere with classification of diabetes and prediabetes using hemoglobin A1c (HbA1c). However, few population-based studies of diabetes in areas with endemic ID/anemia have been conducted. We aimed to determine how mutually exclusive categories of ID alone, anemia alone and iron-deficiency anemia (IDA) were each associated with prediabetes and diabetes prevalence using fasting blood glucose (FBG) versus HbA1c in a population-based study of adults with endemic ID/anemia. We used data from the China Health and Nutrition Survey, a longitudinal, population-based study across 228 communities within nine provinces of China. This analysis included 7308 adults seen in the 2009 survey aged 18-75 years. We used descriptive and covariate-adjusted models to examine relative risk of prediabetes and diabetes using FBG alone, HbA1c alone, HbA1c and FBG, or neither (normoglycemia) by anemia alone, ID alone, IDA or normal iron/hemoglobin. Approximately 65% of individuals with diabetes in our sample were concordantly classified with diabetes using both FBG and HbA1c, while 35% had a discordant diabetes classification: they were classified using either FBG or HbA1c, but not both. Fewer participants with ID alone versus normal iron/hemoglobin were classified with diabetes using HbA1c only. From covariate-adjusted, multinomial regression analyses, the adjusted prevalence of prediabetes using HbA1c only was 22% for men with anemia alone, but 13% for men with normal iron/hemoglobin. In contrast, the predicted prevalence of prediabetes using HbA1c only was 8% for women with ID alone, compared with 13% for women with normal iron/hemoglobin. These findings suggest potential misclassification of diabetes using HbA1c in areas of endemic ID/anemia. Estimating diabetes prevalence using HbA1c may result in under-diagnosis in women with ID and over-diagnosis in men with anemia.

  16. Source Terms for HFIR Beam Tube Shielding Analyses, and a Complete Shielding Analysis of the HB-3 Tube

    Energy Technology Data Exchange (ETDEWEB)

    Bucholz, J.A.


    The High Flux Isotope Reactor (HFIR) at the Oak Ridge National Laboratory is in the midst of a massive upgrade program to enhance experimental facilities. The reactor presently has four horizontal experimental beam tubes, all of which will be replaced or redesigned. The HB-2 beam tube will be enlarged to support more guide tubes, while the HB-4 beam tube will soon include a cold neutron source.

  17. Omp85Tt from Thermus thermophilus HB27 : an Ancestral Type of the Omp85 Protein Family


    Nesper, Jutta; Brosig, Alexander; Ringler, Philippe; Patel, Geetika J.; Müller, Shirley A.; Kleinschmidt, Jörg; Boos, Winfried; Diederichs, Kay; Welte, Wolfram


    Proteins belonging to the Omp85 family are involved in the assembly of β-barrel outer membrane proteins or in the translocation of proteins across the outer membrane in bacteria, mitochondria, and chloroplasts. The cell envelope of the thermophilic bacterium Thermus thermophilus HB27 is multilayered, including an outer membrane that is not well characterized. Neither the precise lipid composition nor much about integral membrane proteins is known. The genome of HB27 encodes one Omp85-like pro...

  18. Trimester-specific reference intervals for haemoglobin A(1c) (HbA(1c)) in pregnancy.

    LENUS (Irish Health Repository)

    O'Connor, Catherine


    Abstract Background: Diabetes in pregnancy imposes additional risks to both mother and infant. These increased risks are considered to be primarily related to glycaemic control which is monitored by means of glycated haemoglobin (HbA(1c)). The correlation of HbA(1c) with clinical outcomes emphasises the need to measure HbA(1c) accurately, precisely and for correct interpretation, comparison to appropriately defined reference intervals. Since July 2010, the HbA(1c) assay in Irish laboratories is fully metrologically traceable to the IFCC standard. The objective was to establish trimester-specific reference intervals in pregnancy for IFCC standardised HbA(1c) in non-diabetic Caucasian women. Methods: The authors recruited 311 non-diabetic Caucasian pregnant (n=246) and non-pregnant women (n=65). A selective screening based on risk factors for gestational diabetes was employed. All subjects had a random plasma glucose <7.7 mmol\\/L and normal haemoglobin level. Pregnancy trimester was defined as trimester 1 (T1, n=40) up to 12 weeks +6 days, trimester 2 (T2, n=106) 13-27 weeks +6 days, trimester 3 (T3, n=100) >28 weeks to term. Results: The normal HbA(1c) reference interval for Caucasian non-pregnant women was 29-37 mmol\\/mol (Diabetes Control and Complications Trial; DCCT: 4.8%-5.5%), T1: 24-36 mmol\\/mol (DCCT: 4.3%-5.4%), T2: 25-35 mmol\\/mol (DCCT: 4.4%-5.4%) and T3: 28-39 mmol\\/mol (DCCT: 4.7%-5.7%). HbA(1c) was significantly decreased in trimesters 1 and 2 compared to non-pregnant women. Conclusions: HbA(1c) trimester-specific reference intervals are required to better inform the management of pregnancies complicated by diabetes.

  19. Capillarys 2 Flex Piercing: Analytical performance assessment according to CLSI protocols for HbA1c quantification. (United States)

    Doggui, Radhouene; Abdelhafidh Sahli, Chaïma; Aissa, Wassef Lotfi; Hammami, Maroua; Ben Sedrine, Maha; Mahjoub, Rahma; Zouaoui, Khemais; Daboubi, Rim; Siala, Hajer; Messaoud, Taieb; Bibi, Amina


    HbA1c is used for monitoring diabetic balance. In this paper we report an assessment of the analytical performances of Capillarys 2 Flex Piercing (C2FP) for HbA1c measurement using CE (Capillary Electrophoresis). CLSI (Clinical and Laboratory Standard Institute) protocols are used for the evaluation of apparatus performances: precision, linearity, method comparison, trueness and common interferences. HbA1c CVs average in intra-assay was 1.6% between run imprecision CV ranged from 0.1 to 1.8%. The linearity was demonstrated between 4.7 and 15.0%. The comparison study revealed that Bland Altman plot mean difference was equal to -0.03 (CI 95% (-0.05 to -0.0003)) and Passing-Bablok regression intercept was -0.05, CI95%(-0.13 -  -0.05); slope: 1.00, CI95%[1.00-1.01]. A strong correlation (r > 0.99) was proved. No significant effects of hemoglobin variants were seen with CE on HbA1c measurement. No problem related to sample-to-sample carry over was noted. No interferences of LA1c and cHb were observed. CE allowed quantification of HbA1c even at low level of total hemoglobin (40 g/L) in contrast to HPLC. Furthermore, this analyzer offered the opportunity of quantifying the HbA2 simultaneously with HbA1c . This evaluation showed that C2FP is a convenient system for the control of diabetes and the detection of hemoglobinopathies. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Identification of Hb Constant Spring (HBA2: c.427T > C) by an Automated High Performance Liquid Chromatography Method. (United States)

    Wisedpanichkij, Raewadee; Jindadamrongwech, Sumalee; Butthep, Punnee


    Laboratory investigation of hemoglobinopathies includes complete blood count (CBC), hemoglobin (Hb) typing by high performance liquid chromatography (HPLC) and DNA analysis. DNA analysis is the most reliable method but requires a manually laborious procedure and is time consuming. A more practical method of detecting abnormal Hbs is the HPLC technique, because it is more rapid and easier to interpret. Hb Constant Spring (Hb CS; HBA2: c.427T > C) is an abnormal variant that is labile and difficult to detect using conventional methods. To evaluate the efficiency of Hb CS determination by HPLC, blood samples from 578 subjects were analyzed using an automated cell analyzer for hematological parameters, automated HPLC for Hb identification, and polymerase chain reaction (PCR) for α-thalassemia (α-thal) and Hb CS confirmation. These included 169 normal, 119 heterozygous α-thal-2, 30 homozygous α-thal-2, 177 heterozygous α-thal-1, 59 heterozygous Hb CS, seven homozygous Hb CS and 17 compound heterozygous α-thal-2 and Hb CS subjects. The results showed that sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of Hb CS by HPLC were 93.78, 99.80, 98.73 and 99.00%, respectively. The mean of misdiagnosis value of the three groups of Hb CS subjects (total 83) was 6.02% (n = 5), with percentages for heterozygous Hb CS, homozygous Hb CS, and compound heterozygous α-thal-2 and Hb CS being 6.8, 0.0 and 5.9%, respectively. The HPLC method yielded good results, although it may also lead to misdiagnosis of Hb CS due to the relatively small amount and lability.

  1. Self-knowledge of HbA1c in people with Type 2 Diabetes Mellitus and its association with glycaemic control. (United States)

    Trivedi, Hina; Gray, Laura J; Seidu, Samuel; Davies, Melanie J; Charpentier, Guillaume; Lindblad, Ulf; Kellner, Christiane; Nolan, John; Pazderska, Agnieszka; Rutten, Guy; Trento, Marina; Khunti, Kamlesh


    The aim of this study was to evaluate the prevalence of accurate self-knowledge of a patient's own HbA1c level (HbA1cSK), as a component of structural education (University Hospital's of Leicester (UHL), 2013) and its association with glycaemic control. Data from the GUIDANCE study, a cross-sectional study involving 7597 participants from eight European countries was used. HbA1cSK was evaluated and compared with laboratory measured HbA1c levels (HbA1cLAB), which represented the measure of glycaemic control. Accuracy of the self-reported HbA1c was evaluated by using agreement statistical methods. The prevalence of HbA1cSK was 49.4%. Within this group, 78.3% of the participants had accurately reported HbA1cSK. There was good level of agreement between HbA1cSK and HbA1cLAB (intra-class correlation statistic=0.84, p<0.0001). Participants with accurately reported HbA1cSK were found to have a statistically significantly lower HbA1cLAB compared to participants with inaccurately reported HbA1cSK (7.0% versus 7.3%, p<0.001). Nearly half of the patients had self-knowledge of their own HbA1c level. Moreover, the participants with accurately reported HbA1cSK were found to have associated better glycaemic control. Copyright © 2017 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

  2. Proton capture reaction cross section measurements on 162Er as a probe of statistical model calculations (United States)

    Özkan, N.; Güray, R. T.; Yalçın, C.; Tan, W. P.; Aprahamian, A.; Beard, M.; deBoer, R. J.; Almaraz-Calderon, S.; Falahat, S.; Görres, J.; Li, Q.; Sauerwein, A.; Sonnabend, K.; Wiescher, M.; Fülöp, Zs.; Gyürky, Gy.; Somorjai, E.; Greene, J.


    It is crucial to measure reaction cross sections relevant to the astrophysical γ process so that theoretical reaction rates can be tested and validated with experimental data. The total cross sections for the 162Er(p ,γ )163Tm and the 162Er(p ,n )162Tm reactions have been measured by the activation method in center-of-mass energies from 3.973 to 8.944 MeV and from 5.962 to 8.944 MeV, respectively. The nucleus 162Er is the heaviest p nuclide to be measured by the activation method using γ -ray spectroscopy, so far. It is important to note that the energy range for the (p ,γ ) reaction measurement covers a large fraction of the astrophysically relevant energy region between 2.71 and 5.34 MeV. The targets were prepared by evaporating 28.2 % isotopically enriched Er1622O3 powder onto carbon backing foils, and bombarded with proton beams provided by the FN Tandem Accelerator at the University of Notre Dame. The reaction yields have been determined by the observed activity of produced radioactive isotopes, which was detected offline by a high-purity germanium detector. The results are presented and compared with calculations from two statistical model codes: non-smoker and talys.

  3. Association between HbA1c and carotid atherosclerosis among elderly Koreans with normal fasting glucose.

    Directory of Open Access Journals (Sweden)

    Seung Won Lee

    Full Text Available We examined whether glycated haemoglobin (HbA1c is associated to carotid atherosclerosis in an elderly Korean population with normal fasting glucose.Using data from the Korean Urban Rural Elderly study, we conducted a cross-sectional analysis of 1,133 participants (335 men and 798 women with a mean age of 71.8 years. All participants had fasting blood glucose less than 100mg/dL (5.6 mmol/L and HbA1c level below 6.5% (48 mmol/mol. They were also free from a history of cardiovascular disease, known type 2 diabetes mellitus or use of anti-diabetes medications. Carotid atherosclerosis was assessed by intima-media thickness (IMT using ultrasonography. The association between HbA1c and carotid IMT was investigated using multivariable linear regression analysis.HbA1c levels were independently and positively associated with carotid IMT (β = 0.020, p = 0.045 after adjusting for sex, age, body mass index, systolic blood pressure, diastolic blood pressure, triglyceride, LDL cholesterol, smoking and alcohol intake. However, fasting insulin and glucose levels were not associated with carotid IMT.HbA1c levels were positively associated with carotid atherosclerosis, as assessed by carotid IMT, in an elderly population with normoglycemia. Our study suggested that higher HbA1c level is an effective and informative marker of carotid atherosclerosis in an elderly population.

  4. Analysis of glycosylated hemoglobin (HbA1c) level on maxillofacial fascial space infection in diabetic patients (United States)

    Jang, Jong-Won; Kim, Moon-Young


    Objectives This study was performed to evaluate the impact of glycosylated hemoglobin (HbA1c) level on characteristics and prognosis of maxillofacial fascial infection in diabetic patients. Materials and Methods We reviewed the medical records of 72 patients (35 patients with HbA1c lower than 7.0% and 37 patients with HbA1c higher than 7.0%) diagnosed with maxillofacial fascial space infection and hospitalized for treatment at the Department of Oral and Maxillofacial Surgery in Dankook University Hospital (Cheonan, Korea) from January 2005 to February 2014. We compared demographics, parameters of glucoregulation (HbA1c), laboratory parameters of inflammation (white blood cell [WBC], C-reactive protein [CRP] count), type and number of involved spaces, type and number of antibiotics, period of hospitalization, number of surgical operations, need for tracheostomy, complications, computed tomography (CT), and microorganisms between the two groups. Results Compared with the well-controlled diabetes mellitus (DM) group (HbA1c maxillofacial fascial infection. Poorly controlled DM with high HbA1c level negatively influences the prognosis of infection. PMID:26568927

  5. Ethnicity modifies the relation between fasting plasma glucose and HbA1c in Indians, Malays and Chinese. (United States)

    Venkataraman, K; Kao, S L; Thai, A C; Salim, A; Lee, J J M; Heng, D; Tai, E S; Khoo, E Y H


    To study whether HbA(1c) , and its relationship with fasting plasma glucose, was significantly different among Chinese, Malays and Indians in Singapore. A sample of 3895 individuals without known diabetes underwent detailed interview and health examination, including anthropometric and biochemical evaluation, between 2004 and 2007. Pearson's correlation, analysis of variance and multiple linear regression analyses were used to examine the influence of ethnicity on HbA(1c) . As fasting plasma glucose increased, HbA(1c) increased more in Malays and Indians compared with Chinese after adjustment for age, gender, waist circumference, serum cholesterol, serum triglyceride and homeostasis model assessment of insulin resistance (P-interaction fasting plasma glucose 5.6 mmol/l (the American Diabetes Association criterion for impaired fasting glycaemia); and 2.1 mmol/mol (0.19%, Indians vs. Chinese) and 2.6 mmol/mol (0.24%, Malays vs. Chinese) at fasting plasma glucose 7.0 mmol/l, the diagnostic criterion for diabetes mellitus. Using HbA(1c) in place of fasting plasma glucose will reclassify different proportions of the population in different ethnic groups. This may have implications in interpretation of HbA(1c) results across ethnic groups and the use of HbA(1c) for diagnosing diabetes mellitus. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.

  6. The Chinese medicine formula HB01 reduces choroidal neovascularization by regulating the expression of vascular endothelial growth factor

    Directory of Open Access Journals (Sweden)

    Jin Ming


    Full Text Available Abstract Background Choroidal neovascularization (CNV remains the leading cause of newly acquired blindness in the developed world. Currently anti-vascular endothelial growth factor (VEGF therapies are broadly used to treat neovascular ocular disorders. Here we demonstrate the effect of a traditional Chinese medicine formula, HB01, on CNV. Methods A rat model of laser-induced CNV was used to investigate the effect of HB01 in vivo. The CNV lesions in the eye were evaluated using fundus fluorescein angiography and visualized/quantified using confocal microscopy. Expression of VEGF in the choroidal and retinal tissues was measured using quantitative real-time PCR and immunohistochemistry. Results We demonstrated that a traditional Chinese Medicine formula, named HB01, significantly reduced neovascularization in a rat CNV model. The effect of HB01 on CNV was comparable to the intravitreal injection of bevacizumab (Avastin. Our results also suggested that HB01 may reduce CNV partially through inhibiting the expression of VEGF. Conclusions These data support HB01 as an alternative therapy for ocular neovascular disorders.

  7. Laboratory diagnosis of a compound heterozygosity for Hb Hekinan [alpha27(B8) Glu-Asp] and a deletional alpha-thalassaemia 2 in Thailand. (United States)

    Chunpanich, S; Ayukarn, K; Sanchaisuriya, K; Fucharoen, G; Fucharoen, S


    We report the haematological and molecular characterization of a previously undescribed condition of compound heterozygosity for haemoglobin (Hb) Hekinan [alpha27(B8) Glu-Asp] and a deletional alpha-thalassaemia 2 detected in a Thai individual. Hb analysis demonstrated that although this Hb variant co-migrates with Hb A on cellulose acetate electrophoresis and cation-exchange high-performance liquid chromatography (HPLC), the HPLC procedure using a weak cation-exchange material with polyaspartic acid could clearly differentiate the two Hb. The variant could then be confirmed using the polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) analysis of the amplified alpha1-globin gene.

  8. Evaluation of the HB&L system for the culture of prosthetic and osteoarticular origin samples

    Directory of Open Access Journals (Sweden)

    Agostina Ronca


    Full Text Available Prosthetic and osteoarticular infections represent a complex condition to diagnose and resolve. In both cases, the eradication of microorganisms is difficult because of anatomical and physiological characteristics of the site of infection (bone.The best strategy for an effective pharmacological treatment is based on an early diagnosis confirmed by microbiological testing of bone, periprosthetic tissue or removed prostheses, to support clinicians to undertake prolonged targeted therapy. The purpose of this paper is to assess the clinical correlation between the results of the cultures performed with automated HB&L (ALIFAX system compared to the result of traditional methods. HB&L is a system to perform bacterial cultures, susceptibility and direct P.A.R. tests on biological materials based on detection of bacteria and fungi by laser light-scattering kinetics in liquid culture medium at 37°C. Samples get to laboratory are inoculated in rich broth and placed in the incubator. The next day are processed accordin to the following protocol: 500 ml of the broth are transferred in the vial of the instrument and 200 ml of supplement DEB for fastidious organisms are added.The cultures are incubated for 360 minutes in the same time PAR test (antimicrobial residual power is determined. In the first half of 2009 418 samples collected from prostheses and osteoarticular infections from 118 patients were analyzed.The tests showed 304 negative and 114 positive samples (27.30% from which were isolated Gram negative (17.5% and Gram positive (82.5% bacteria. Gram positive included 38.3% S. aureus, 33% coagulase negative Staphylococci and 26.6% Enterococci. Preliminary data obtained by the HB&L system for the culture of tissue sample, as well as the improvement of surgical techniques have led to a significant increase in correlation with the clinical data compared to traditional microbiological analysis.

  9. Interaction between the Supernova Remnant HB 3 and the Nearby Star-forming Region W3 (United States)

    Zhou, Xin; Yang, Ji; Fang, Min; Su, Yang; Sun, Yan; Chen, Yang


    We performed millimeter observations of CO lines toward the supernova remnant (SNR) HB 3. Substantial molecular gas around -45 km s-1 is detected in the conjunction region between the SNR HB 3 and the nearby W3 complex. This molecular gas is distributed along the radio continuum shell of the remnant. Furthermore, the shocked molecular gas indicated by line wing broadening features is also distributed along the radio shell and inside it. By both morphological correspondence and dynamical evidence, we confirm that the SNR HB 3 interacts with the -45 km s-1 molecular cloud (MC), in essence, with the nearby H ii region/MC complex W3. The redshifted line wing broadening features indicate that the remnant is located at the nearside of the MC. With this association, we could place the remnant at the same distance as the W3/W4 complex, which is 1.95 ± 0.04 kpc. The spatial distribution of aggregated young stellar object candidates shows a correlation with the shocked molecular strip associated with the remnant. We also find a binary clump of CO at (l = 132.°94, b = 1.°12) around -51.5 km s-1 inside the projected extent of the remnant, and it is associated with significant mid-infrared emission. The binary system also has a tail structure resembling the tidal tails of interacting galaxies. According to the analysis of CO emission lines, the larger clump in this binary system is about stable, and the smaller clump is significantly disturbed.

  10. HB&L System: rapid determination of antibiotic sensitivity of bacteria isolated from blood cultures.

    Directory of Open Access Journals (Sweden)

    Simone Barocci


    Full Text Available Introduction. Blood culture is an important method to detect microbial pathogens on blood, very useful for diagnosing bacterial infections. Unfortunately, classical diagnostic protocols cannot directly identify bacteria responsible for sepsis and accordingly their antimicrobial profiles. This problem causes a delay of almost two days in the availability of a specific antimicrobial profile. Objective. Among the main causes of death, sepsis have a relevant importance. For this reason it is important both to identify pathogens and to perform an antimicrobial susceptibility test in the shortest time as possible. For this purpose, the main aim of this study is the evaluation of the performances of an antimicrobial susceptibility determination directly performed on positive blood cultures. Materials and methods. This study has been performed on 70 positive blood cultures, during the period from January to July 2009. A number of 35 blood cultures were positive for Gram negative bacteria, and 35 were positive for Gram positive bacteria. From these positive blood cultures, after a short sample preparation, it has been possible to directly determine antimicrobial susceptibility profiles by using the HB&L (formerly URO-QUICK instrument. Results. The HB&L system results showed a very good correlation with both the classical disk diffusion method and VITEK 2 automatic system.The performances between the methods carried out in this study were equivalent. Conclusions. From data reported, thanks to the rapidity and simplicity of the method used, we can assert that the direct susceptibility test available with the HB&L system, is useful for a rapid and early choice of the antibiotic treatment.

  11. Statins are independently associated with increased HbA1c in type 1 diabetes

    DEFF Research Database (Denmark)

    Jensen, Magnus Thorsten; Andersen, Henrik Ullits; Rossing, Peter


    ventricular ejection fraction was not associated with statin use. In multivariable models including age, gender, diabetes duration, BMI, blood pressure, physical activity, family history of cardiovascular disease, physical activity, albuminuria, eGFR, retinopathy, smoking, cholesterol, ejection fraction......, triglycerides, and use of ACE/ATII-antagonists, aspirin, calcium-antagonists, betablockers or diuretics, statin use was independently and significantly associated with higher HbA1c (0.2% (95%CI: 0.1; 0.4) (2.0mmol/mol (0.2; 3.8)), p=0.029). CONCLUSIONS: In T1DM, use of statins is independently associated...

  12. Muscle pathology in lower motor neuron paraplegia and h-b FES

    Directory of Open Access Journals (Sweden)

    Ugo Carraro


    Full Text Available After complete Spinal Cord Injury (SCI, causing complete disconnection between the muscle fibers and the nervous system, the denervated muscles become unexcitable with commercial electrical stimulators within several months and undergo severe atrophy and disorganization of contractile apparatus after 1-3 years. Years after the injury the surviving and regenerated myofibers are substituted with adipocytes and collagen. To counteract the progressive changes transforming muscle into an unexcitable tissue, we developed a novel therapy concept for paraplegic patients with complete lower motor neuron (LMN denervation of the lower extremities. The new stimulators for home-based functional electrical stimulation (h-b FES have been designed to reverse longstanding and severe atrophy of LMN denervated muscles by delivering high-intensity (up to 2,4 J and long-duration impulses (up to 150 ms able to elicit contractions of denervated skeletal muscle fibers in absence of nerve. Concurrent to the development of the stimulation equipment, specific clinical assessments and training strategies were developed at the Wilhelminenspital Wien, Austria. Main results of our clinical study on 20 patients, which completed a 2 years h-b FES program are: 1. significant +33% increase of muscle size and +75% of the mean diameter of muscle fibers, with striking improvements of the ultra-structural organization of contractile material; 2. recovery of the tetanic contractility with significant increase in muscle force output during electrical stimulation; 3. five subjects performed FES-assisted stand-up and stepping-in-place exercises;. 4. data from ultrastructural analyses indicating that the shorter the time span between SCI and the beginning of h-b FES, the larger were the number and the size of recovered fibers. The study demonstrates that h-b FES of permanent LMN denervated muscle is an effective home therapy that results in rescue of muscle mass, function and perfusion

  13. HbA1c, diabetes and cognitive decline: the English Longitudinal Study of Ageing. (United States)

    Zheng, Fanfan; Yan, Li; Yang, Zhenchun; Zhong, Baoliang; Xie, Wuxiang


    The aim of the study was to evaluate longitudinal associations between HbA1c levels, diabetes status and subsequent cognitive decline over a 10 year follow-up period. Data from wave 2 (2004-2005) to wave 7 (2014-2015) of the English Longitudinal Study of Ageing (ELSA) were analysed. Cognitive function was assessed at baseline (wave 2) and reassessed every 2 years at waves 3-7. Linear mixed models were used to evaluate longitudinal associations. The study comprised 5189 participants (55.1% women, mean age 65.6 ± 9.4 years) with baseline HbA1c levels ranging from 15.9 to 126.3 mmol/mol (3.6-13.7%). The mean follow-up duration was 8.1 ± 2.8 years and the mean number of cognitive assessments was 4.9 ± 1.5. A 1 mmol/mol increment in HbA1c was significantly associated with an increased rate of decline in global cognitive z scores (-0.0009 SD/year, 95% CI -0.0014, -0.0003), memory z scores (-0.0005 SD/year, 95% CI -0.0009, -0.0001) and executive function z scores (-0.0008 SD/year, 95% CI -0.0013, -0.0004) after adjustment for baseline age, sex, total cholesterol, HDL-cholesterol, triacylglycerol, high-sensitivity C-reactive protein, BMI, education, marital status, depressive symptoms, current smoking, alcohol consumption, hypertension, CHD, stroke, chronic lung disease and cancer. Compared with participants with normoglycaemia, the multivariable-adjusted rate of global cognitive decline associated with prediabetes and diabetes was increased by -0.012 SD/year (95% CI -0.022, -0.002) and -0.031 SD/year (95% CI -0.046, -0.015), respectively (p for trend <0.001). Similarly, memory, executive function and orientation z scores showed an increased rate of cognitive decline with diabetes. Significant longitudinal associations between HbA1c levels, diabetes status and long-term cognitive decline were observed in this study. Future studies are required to determine the effects of maintaining optimal glucose control on the rate of cognitive decline in people

  14. Registration of a High Yielding Malt Barley Variety HB1454 for the ...

    African Journals Online (AJOL)


    Registration of a High Yielding Malt Barley Variety. HB1454 for the Potential Highlands of Ethiopia. Berhane Lakew and Wondimu Fekadu. EIAR, Holetta Research Center, P O Box- 2003, Addis Ababa. አህፅርኦት. ኤች ቢ1454 የተባሇው ባሇሁሇት መስመር የብቅል ገብስ ዝርያ የተመዘገበበት ስም EH 1847/F4.2P.5.2). ሲሆን በሆሇታ ...

  15. Multicentre evaluation of the Tosoh HbA1c G8 analyser. (United States)

    Chapelle, Jean-Paul; Teixeira, Jelda; Maisin, Diane; Assink, Hans; Barla, Gerhard; Stroobants, An K; Delzenne, Barend; van den Eshof, Wouter


    We report a Dutch-Belgian multicentre evaluation of the Tosoh HLC-723G8 glycohaemoglobin analyser, an ion-exchange HPLC instrument for the separation and quantification of haemoglobin A1c (HbA1c) in whole blood. We evaluated the analytical performances of the Tosoh G8 analyser and compared the results for blood samples with its predecessor, the Tosoh G7, and with two other widely used analysers, the Bio-Rad Variant II and Adams Arkray HA-8160. Within- and between-batch imprecision [coefficient of variation (CVs)] was G8 analyser can be considered to be state of the art.

  16. Interaction of - α 3.7, ß Thalassemia Mutation IVS 1-5 and HbD Punjab in a Family: A Case Report. (United States)

    Pandey, S; Ranjan, Ravi; Mishra, R M; Pandey, Sw; Saxena, R


    Hemoglobin D exist in four form; HbD trait, HbD-thalassemia, HbD sickle cell and HbD homozygous. HbD trait and HbD homozygous generally asymptomatic condition but when HbD co-inherit with thalassemia and sickle cell anemia, produces clinically significant conditions like chronic hemolytic anemia. Here we present a case of HbD Punjab with α 3.7 kb deletion and IVS-1-5 β-thalassemia across a family. Diagnosis of HbD patient was performed by high performance liquid chromatography and complete blood count was measured by automated cell analyzer. Molecular study for common alpha deletions done by Gap-PCR while beta thalassemia mutation identified by ARMS-PCR. Case was clinically significant due to the inheritance of HbD/β(+)thalassemia genotype. Thus observed case behaved like thalassemia intermedia due to co-existence of α 3.7 deletions with IVS 1-5 β-thalassemia mutation in HbD Punjab patient.

  17. Severe Hemophilia A in a Male Old English Sheep Dog with a C→T Transition that Created a Premature Stop Codon in Factor VIII (United States)

    Lozier, Jay N; Kloos, Mark T; Merricks, Elizabeth P; Lemoine, Nathaly; Whitford, Margaret H; Raymer, Robin A; Bellinger, Dwight A; Nichols, Timothy C


    Animals with hemophilia are models for gene therapy, factor replacement, and inhibitor development in humans. We have actively sought dogs with severe hemophilia A that have novel factor VIII mutations unlike the previously described factor VIII intron 22 inversion. A male Old English Sheepdog with recurrent soft-tissue hemorrhage and hemarthrosis was diagnosed with severe hemophilia A (factor VIII activity less than 1% of normal). We purified genomic DNA from this dog and ruled out the common intron 22 inversion; we then sequenced all 26 exons. Comparing the results with the normal canine factor VIII sequence revealed a C→T transition in exon 12 of the factor VIII gene that created a premature stop codon at amino acid 577 in the A2 domain of the protein. In addition, 2 previously described polymorphisms that do not cause hemophilia were present at amino acids 909 and 1184. The hemophilia mutation creates a new TaqI site that facilitates rapid genotyping of affected offspring by PCR and restriction endonuclease analyses. This mutation is analogous to the previously described human factor VIII mutation at Arg583, which likewise is a CpG dinucleotide transition causing a premature stop codon in exon 12. Thus far, despite extensive treatment with factor VIII, this dog has not developed neutralizing antibodies (‘inhibitors’) to the protein. This novel mutation in a dog gives rise to severe hemophilia A analogous to a mutation seen in humans. This model will be useful for studies of the treatment of hemophilia. PMID:27780008

  18. The Effectiveness of Team's Game Tournament Seen From Communication and Problem Solveing Capabilities (Experimental Study of Class VIII students in SMP Negeri 1 Seyegan

    Directory of Open Access Journals (Sweden)

    Nuryadi Nuryadi


    Full Text Available Cooperative learning is the type of Team's Games Tournament (TGT which is a learning model in which there are stages such as games which can make the students communicate mathematically, more creative, have a positive attitude towards mathematics, and appropriate in solving mathematical problems. But in fact, communication skills and problem solving that should be owned by the students as a result of the learning process of mathematics meet the minimum completeness criteria (KKM. This study aims to describe the effectiveness of Cooperative learning of TGT type at mathematics learning in terms of communication skills and problem solving in class VIII SMP N 1 Seyegan the school year 2016/2017.  This research is a quasi ekspreriment research with pre-posttest nonequivalent control group design. This study uses two groups: the experimental group and the control group. The population study includes all students of class VIII which consists of four classes. From the existing population, it is drawn randomly two classes, namely VIII A and VIII C as samples. Mathematics Learning in class VIII A (experimental group uses TGT type Cooperative learning and mathematics learning in class VIII C (control group uses direct instruction. The instrument of this study is testing the communication and problem solving capability. To test the effectiveness of the study, it is used the analysis of one sample t-test. Whereas the T2 test hotteling is foolowed by univariate t-test which is used to determine more effective model. The result of research indicates that: (1 Cooperative learning of TGT-type and direct instruction in mathematics is effective in terms of communication skills and problem-solving; and (2 Cooperative learning of TGT type is more effective than direct instruction type in term of communication skill in class VIII SMPN 1 Seyegan.   Keywords: TGT, mathematical communication, problem solving

  19. Impact of fasting and postprandial glycemia on overall glycemic control in type 2 diabetes Importance of postprandial glycemia to achieve target HbA1c levels. (United States)

    Woerle, Hans J; Neumann, Christoph; Zschau, Silvia; Tenner, Stephanie; Irsigler, Andrea; Schirra, Joerg; Gerich, John E; Göke, Burkhard


    HbA1c values reflect overall glycemic exposure over the past 2-3 months and are determined by both fasting (FPG) and postprandial plasma glucose (PPG) levels. Cross-sectional studies suggest that attainment of HbA1c goals requires specific targeting of postprandial hyperglycemia. We undertook a prospective intervention trial to assess the relative contribution of controlling FPG and PPG for achieving recommended HbA1c goals. One hundred and sixty-four patients (90 male and 74 female) with unsatisfactory glycemic control (HbA1c >/=7.5%) were enrolled in an individualized forced titration intensified treatment program. After 3 months HbA1c levels decreased from 8.7+/-0.1 to 6.5+/-0.1% (pfasting hyperglycemia is necessary but usually insufficient for achieving HbA1c goals <7%. Control of postprandial hyperglycemia is essential for achieving recommended HbA1c goals.

  20. Two cases of compound heterozygosity for Hb Hekinan [alpha27(B8)Glu-->Asp (alpha1)] and alpha-thalassemia in Thailand. (United States)

    Ngiwsara, Lukana; Srisomsap, Chantragan; Winichagoon, Pranee; Fucharoen, Suthat; Svasti, Jisnuson


    Two unrelated cases of compound heterozygosity for Hb Hekinan [alpha27(B8)Glu-->Asp (alpha1) and alpha-thalassemia have been found in Thailand. Mutations were established at protein level by peptide mapping and at the DNA level by direct sequence analysis. Proband S.S. had genotype - -SEA/alpha2(A)alpha1Hekinan, betaA/betaE, while an unrelated proband, S.J., is the first case described with the genotype - -SEA/alpha2(A)alpha1Hekinan, betaA/betaA. Both alpha1Hekinan mutations were located in the alpha1 locus. Hb Hekinan could not be accurately estimated by HPLC, since it was poorly separated from Hb A. However IEF gave good separation of Hb Hekinan and Hb A, leading to estimates of Hb Hekinan (alpha Hekinan 2/beta A 2 and alpha Hekinan 2/beta E 2) level as 40-43% of total Hb.


    Directory of Open Access Journals (Sweden)

    Dian Nailis Suroyya


    Full Text Available Tujuan penelitian ini adalah mengetahui apakah apakah rata-rata kemampuan spasial siswa pada kelas yang menggunakan model pembelajaran Novick lebih baik dari rata-rata kemampuan spasial siswa pada kelas yang menggunakan model pembelajaran Direct Instruction, mengetahui apakah rata-rata kemampuan spasial siswa pada kelas yang menggunakan model pembelajaran Group Investigation lebih baik dari rata-rata kemampuan spasial siswa pada kelas yang menggunakan model pembelajaran Direct Instruction, mengetahui apakah rata-rata kemampuan spasial siswa pada kelas yang menggunakan model pembelajaran Novick lebih baik dari rata-rata kemampuan spasial siswa pada kelas yang menggunakan model pembelajaran Group Investigation, dan mengetahui apakah peningkatan kemampuan spasial siswa pada kelas yang menggunakan model pembelajaran Novick lebih baik dari peningkatan kemampuan spasial siswa pada kelas yang menggunakan model pembelajaran Group Investigation. Populasi dalam penelitian ini adalah seluruh siswa kelas VIII MTs N 1 Kudus tahun pelajaran 2013/2014. Pengambilan sampel menggunakan teknik random sampling. Data diperoleh melalui metode tes dan data dianalisis menggunakan uji t. Hasil penelitian menunjukkan bahwa rata-rata kemampuan spasial siswa pada kelas yang menggunakan model pembelajaran Novick dan rata-rata kemampuan spasial siswa pada kelas yang menggunakan model pembelajaran Group Investigation lebih baik dari rata-rata kemampuan spasial siswa pada kelas yang menggunakan model pembelajaran Direct Instruction, rata-rata kemampuan spasial siswa pada kelas yang menggunakan model pembelajaran Novick kurang dari atau sama dengan kemampuan rata-rata kemampuan spasial siswa pada kelas yang menggunakan model pembelajaran Group Investigation, dan peningkatan kemampuan spasial siswa pada kelas yang menggunakan model pembelajaran Novick kurang dari atau sama dengan peningkatan kemampuan spasial siswa pada kelas yang menggunakan model pembelajaran Group

  2. The ABO blood group genotype and factor VIII levels as independent risk factors for venous thromboembolism. (United States)

    Tirado, Isabel; Mateo, José; Soria, José Manuel; Oliver, Arturo; Martínez-Sánchez, Elisabeth; Vallvé, Cristina; Borrell, Monserrat; Urrutia, Teresa; Fontcuberta, Jordi


    Factor VIII (FVIII), von Willebrand factor (vWF) and the ABO blood groups have been associated with thrombosis. The ABO locus has functional effects on vWF and FVIII levels and is genetically correlated with FVIII, vWF and thrombosis. We carried out a case-control study to assess the role of FVIII, vWF and ABO types on thrombotic risk. We analyzed 250 patients with venous thrombosis and 250 unrelated controls. FVIII, vWF and other factors related to thrombophilia were measured, ABO groups were analyzed by genotyping. FVIII and vWF were higher in non-O individuals. Group O was more frequent in the controls (44.3% v 23.3%; difference 21.1%; 95% CI: 13.0-29.3%) and Group A in patients (59.2% v. 41.5%; difference 17.7%, 95% CI: 9.1-26.4%). Individuals carrying the A1 allele had a higher risk of thrombosis (OR 2.6; 95% CI, 1.8-3.8). The risk attributed to vWF disappeared after adjusting for the ABO group. Patients with FVIII above the 90th percentile had a high thrombotic risk (adjusted OR 3.7; 95% CI, 2.1-6.5), and a high risk of recurrence (OR 2.3; 95% CI: 1.3-4.1). In conclusion, high FVIII levels and non-O blood groups, likely those with the A1 allele, are independent risk factors for venous thromboembolism and should be considered in evaluating of thrombophilia.

  3. Frequencies of VNTR and RFLP polymorphisms associated with factor VIII gene in Singapore

    Energy Technology Data Exchange (ETDEWEB)

    Fong, I.; Lai, P.S.; Ouah, T.C. [National Univ. of Singapore (Malaysia)] [and others


    The allelic frequency of any polymorphism within a population determines its usefulness for genetic counselling. This is important in populations of non-Caucasian origin as RFLPs may significantly differ among ethnic groups. We report a study of five intragenic polymorphisms in factor VIII gene carried out in Singapore. The three PCR-based RFLP markers studied were Intron 18/Bcl I, Intron 19/Hind III and Intron 22/Xba I. In an analysis of 148 unrelated normal X chromosomes, the allele frequencies were found to be A1 = 0.18, A2 = 0.82 (Bcl I RFLP), A1 = 0.80, A2 = 0.20 (Hind III RFLP) and A1 = 0.58, and A2 = 0.42 (Xba I RFLP). The heterozygosity rates of 74 females analyzed separately were 31%, 32% and 84.2%, respectively. Linkage disequilibrium was also observed to some degree between Bcl I and Hind III polymorphism in our population. We have also analyzed a sequence polymorphism in Intron 7 using hybridization with radioactive-labelled {sup 32}P allele-specific oligonucleotide probes. This polymorphism was not very polymorphic in our population with only 2% of 117 individuals analyzed being informative. However, the use of a hypervariable dinucleotide repeat sequence (VNTR) in Intron 13 showed that 25 of our of 27 (93%) females were heterozygous. Allele frequencies ranged from 1 to 55 %. We conclude that a viable strategy for molecular analysis of Hemophilia A families in our population should include the use of Intron 18/Bcl I and Intron 22/Xba I RFLP markers and the Intron 13 VNTR marker.

  4. Nonneutralizing antibodies against factor VIII and risk of inhibitor development in severe hemophilia A. (United States)

    Cannavò, Antonino; Valsecchi, Carla; Garagiola, Isabella; Palla, Roberta; Mannucci, Pier Mannuccio; Rosendaal, Frits R; Peyvandi, Flora


    The development of anti-factor VIII (FVIII) neutralizing antibodies (inhibitors) is the major complication in hemophilia A. Nonneutralizing antibodies (NNAs) have been detected in hemophilia patients and also in unaffected individuals. The aim of this study was to assess the prevalence of NNAs and to evaluate whether their presence is associated with the development of inhibitors in a cohort of previously untreated or minimally treated patients with hemophilia A; plasma samples of 237 patients with severe hemophilia A enrolled in the SIPPET trial were collected before any exposure to FVIII concentrates and analyzed for the presence of anti-FVIII NNAs. Patients were observed for the development of neutralizing antibodies. NNAs were found in 18 (7.6%) of 237 patients at screening, and there was a clear age gradient. Of those with NNAs, 7 patients subsequently developed an inhibitor for a cumulative incidence of 45.4% (95% confidence interval [CI], 19.5% to 71.3%); among the 219 patients without NNAs, 64 (29%) developed an inhibitor (cumulative incidence, 34.0%; 95% CI, 27.1%-40.9%). In Cox regression analyses, patients with NNAs at screening had an 83% higher incidence of inhibitor development than patients without NNAs (hazard ratio [HR], 1.83; 95% CI, 0.84-3.99). For high-titer inhibitors, the incidence rate had an almost threefold increase (HR, 2.74; 95% CI, 1.23-6.12). These associations did not materially change after adjustment. The presence of anti-FVIII NNAs in patients with severe hemophilia A who were not previously exposed to FVIII concentrates is associated with an increased incidence of inhibitors. © 2017 by The American Society of Hematology.

  5. Immunoprotective effect of von Willebrand factor towards therapeutic factor VIII in experimental haemophilia A. (United States)

    Delignat, S; Repessé, Y; Navarrete, A-M; Meslier, Y; Gupta, N; Christophe, O D; Kaveri, S V; Lacroix-Desmazes, S


    The development of inhibitory anti-factor VIII (FVIII) antibodies in patients with haemophilia A following replacement therapy is associated with several types of risk factors. Among these, the purity of FVIII concentrates, and in particular the presence of von Willebrand factor (VWF), was controversially proposed to influence the immunogenicity of exogenous FVIII. We re-assessed in vivo and in vitro the immuno-protective effect of VWF towards FVIII. The immuno-protective effect of VWF towards FVIII was investigated in vivo, in a model of haemophilia A. We studied the endocytosis of FVIII by murine bone marrow-derived dendritic cells and evaluated the capacity of VWF to block the internalization of FVIII. We characterized the relevance of VWF for the accumulation of FVIII in the marginal zone of the spleen, a secondary lymphoid organ where the immune response to therapeutically administered FVIII initiates. Our results confirm that VWF reduces the immunogenicity of FVIII in FVIII-deficient mice. Paradoxically, VWF is important for the accumulation of FVIII in the marginal zone of the spleen. We propose that VWF exerts at least two non-mutually exclusive immunoprotective roles towards FVIII in haemophilic mice: VWF prevents the endocytosis of FVIII by professional antigen-presenting cells by blocking the interaction of FVIII with as yet unidentified endocytic receptor(s). Hypothetically, VWF, by virtue of increasing the half-life of FVIII in the circulation, may allow an increased contact time with tolerogenic marginal zone B cells in the spleen. © 2011 Blackwell Publishing Ltd.

  6. Expanding the Ortholog Approach for Hemophilia Treatment Complicated by Factor VIII Inhibitors (United States)

    Zakas, P.M.; Vanijcharoenkarn, K.; Markovitz, R.C.; Meeks, S.L.; Doering, C.B.


    Summary Background The formation of neutralizing antibodies (inhibitors) directed against human coagulation factor VIII (hFVIII) is a life-threatening pathogenic response that occurs in 20–30% of severe congenital hemophilia A patients and 0.00015% of remaining population (i.e. acquired hemophilia A). Interspecies amino acid sequence disparity among FVIII orthologs represents a promising strategy to mask FVIII from existing inhibitors while retaining procoagulant function. Evidence for the effectiveness of this approach exists in clinical data obtained for porcine FVIII products, which have demonstrated efficacy in the setting of congenital and acquired hemophilia. Objectives In the current study, recombinant (r) ovine FVIII (oFVIII), was evaluated for antigenicity and procoagulant activity in the context of human patient-derived and murine model-generated FVIII inhibitors. Methods The antigenicity of roFVIII was assessed using i) inhibitor patient plasma samples, ii) murine anti-FVIII MAbs, iii) immunized murine hemophilia A plasmas, and iv) an in vivo model of acquired hemophilia A Results Overall, roFVIII demonstrated reduced reactivity to, and inhibition by, anti-hFVIII immunoglobulin in patient plasmas. Additionally, several hFVIII epitopes were predicted and empirically shown not to exist within roFVIII. In a murine hemophilia A model designed to mimic clinical inhibitor formation, it was demonstrated that inhibitor titers to roFVIII were significantly reduced compared to the orthologous immunogens, rhFVIII or rpFVIII. Furthermore in a murine model of acquired hemophilia A, roFVIII administration conferred protection from bleeding following tail transection. Conclusion These data support the investigation of FVIII orthologs as treatment modalities in both the congenital and acquired FVIII inhibitor settings. PMID:25315236

  7. Rancang Bangun Perangkat Eksperimen Hukum Archimedes untuk MTs LB/A Yaketunis Kelas VIII

    Directory of Open Access Journals (Sweden)

    Rofiqoh Utami


    Full Text Available Blind students find difficulties whenever they are involved in the experiment of Archimedes principle as it requests an active visual role. Thus, it is very important to design a special tool for blind students so their practice of Archimedes principle become easier. This paper discusses a research finding which is an innovation of adaptive tools for blind students, such as beaker glass with Braille number, dynamometer with modification and Braille number (Braille Spring Balance and recording lesson about Archimedes principle. This research done for students MTs LB / A Yaketunis Class VIII which aims at analyzing the quality of each tool by media experts, lesson experts, and physics teacher of MTs LB/A.This research is R & D with procedural models adapted from the development of the 4-D models, namely Define, Design, Develop, and Disseminate. According to media expert assessment, beaker glass with Braille number and Braille spring balance has a very good quality with percentage of their respective 100% of the ideal score, while the assessment by lesson experts for each tool have a good quality with percentage 80% and 73.33% of the ideal score, and physics teacher of MTs LB / A assessment for each tool have a very good quality with percentage 100%. According to the media and lesson experts, the recording lesson about Archimedes principle have a good quality with percentage 80% of the ideal score, according to physics teacher MTs LB / A, the recording tool has excellent quality either with percentage 91.82% of the ideal score. This research recommends the blinds students to utilize these innovative-adaptive tools which will enable them appropriately practice Archimedes principle as non-blind students.

  8. A Model for Predicting Persistent Elevation of Factor VIII among Patients with Acute Ischemic Stroke. (United States)

    Samai, Alyana A; Boehme, Amelia K; Shaban, Amir; George, Alexander J; Dowell, Lauren; Monlezun, Dominique J; Leissinger, Cindy; Schluter, Laurie; El Khoury, Ramy; Martin-Schild, Sheryl


    Elevated levels of coagulation factor VIII (FVIII) may persist independent of the acute-phase response; however, this relationship has not been investigated relative to acute ischemic stroke (AIS). We examined the frequency and predictors of persistently elevated FVIII in AIS patients. AIS patients admitted between July 2008 and May 2014 with elevated baseline FVIII levels and repeat FVIII levels drawn for more than 7 days postdischarge were included. The patients were dichotomized by repeat FVIII level for univariate analysis at 150% and 200% activity thresholds. An adjusted model was developed to predict the likelihood of persistently elevated FVIII levels. Among 1616 AIS cases, 98 patients with elevated baseline FVIII had repeat FVIII levels. Persistent FVIII elevation was found in more than 75% of patients. At the 150% threshold, the prediction score ranged from 0 to 7 and included black race, female sex, prior stroke, hyperlipidemia, smoking, baseline FVIII > 200%, and baseline von Willebrand factor (vWF) level greater than 200%. At the 200% threshold, the prediction score ranged from 0-5 and included female sex, prior stroke, diabetes mellitus, baseline FVIII level greater 200%, and baseline vWF level greater than 200%. For each 1-point increase in score, the odds of persistent FVIII at both the 150% threshold (odds ratio [OR] = 10.4, 95% confidence interval [CI] 1.63-66.9, P = .0134) and 200% threshold (OR = 10.2, 95% CI 1.82-57.5, P = .0083) increased 10 times. Because an elevated FVIII level confers increased stroke risk, our model for anticipating a persistently elevated FVIII level may identify patients at high risk for recurrent stroke. FVIII may be a target for secondary stroke prevention. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  9. Enhanced factor VIII heavy chain for gene therapy of hemophilia A. (United States)

    Chen, Lingxia; Lu, Hui; Wang, Jinhui; Sarkar, Rita; Yang, Xiao; Wang, Hongli; High, Katherine A; Xiao, Weidong


    Hemophilia A gene therapy using recombinant adenovirus-associated virus (AAV) vectors has been hampered by the size of the factor VIII (FVIII) cDNA. Previously, splitting the FVIII coding sequence into a heavy-chain (HC) fragment and a light-chain (LC) fragment for dual recombinant AAV vector delivery has been successfully explored. However, the main disadvantage of this approach is a "chain imbalance" problem in which LC secretion is approximately 1-2 logs higher than that of HC, and therefore, the majority of protein synthesized is nonfunctional. To improve HC secretion, we constructed alternate FVIII HCs based on our observation that LC facilitates HC secretion. To our surprise, most of the new HC molecules exhibited enhanced expression over the traditional HC molecule (HC(745)). The optimized HC mutein, HC(HL), including additional acidic-region-3 (ar3) sequences, exhibited three- to fivefold higher activity in both enzyme-linked immunosorbent assay (ELISA) and activated partial thromboplastin time (aPTT) assay in in vitro testing. Further characterization suggested ar3 sequences increased HC secretion, rather than promoting HC synthesis. Intravenous delivery of AAV8-HC(HL)+AAV8-LC or AAV8-HC(745)+AAV8-LC achieved phenotypic correction in hemophilia A mice. Mice receiving AAV8-HC(HL)+AAV8-LC achieved three- to fourfold higher HC expression than AAV8-HC(745)+AAV8-LC, consistent with the FVIII functional assays. HC(HL) should be substituted for HC(745) in a dual AAV vector strategy due to its enhanced expression.

  10. Intraosseous delivery of lentiviral vectors targeting factor VIII expression in platelets corrects murine hemophilia A. (United States)

    Wang, Xuefeng; Shin, Simon C; Chiang, Andy F J; Khan, Iram; Pan, Dao; Rawlings, David J; Miao, Carol H


    Intraosseous (IO) infusion of lentiviral vectors (LVs) for in situ gene transfer into bone marrow may avoid specific challenges posed by ex vivo gene delivery, including, in particular, the requirement of preconditioning. We utilized IO delivery of LVs encoding a GFP or factor VIII (FVIII) transgene directed by ubiquitous promoters (a MND or EF-1α-short element; M-GFP-LV, E-F8-LV) or a platelet-specific, glycoprotein-1bα promoter (G-GFP-LV, G-F8-LV). A single IO infusion of M-GFP-LV or G-GFP-LV achieved long-term and efficient GFP expression in Lineage(-)Sca1(+)c-Kit(+) hematopoietic stem cells and platelets, respectively. While E-F8-LV produced initially high-level FVIII expression, robust anti-FVIII immune responses eliminated functional FVIII in circulation. In contrast, IO delivery of G-F8-LV achieved long-term platelet-specific expression of FVIII, resulting in partial correction of hemophilia A. Furthermore, similar clinical benefit with G-F8-LV was achieved in animals with pre-existing anti-FVIII inhibitors. These findings further support platelets as an ideal FVIII delivery vehicle, as FVIII, stored in α-granules, is protected from neutralizing antibodies and, during bleeding, activated platelets locally excrete FVIII to promote clot formation. Overall, a single IO infusion of G-F8-LV was sufficient to correct hemophilia phenotype for long term, indicating that this approach may provide an effective means to permanently treat FVIII deficiency.

  11. Impact of being overweight on factor VIII dosing in children with haemophilia A. (United States)

    Henrard, S; Hermans, C


    Treatment of haemophilia A (HA) requires infusions of factor VIII (FVIII) concentrates. The number of FVIII units infused to obtain a specific circulating FVIII level is calculated with the formula: [body weight (BW) (kg) × desired FVIII increase (%)]/2, with the assumption that each unit of FVIII infused per kg of BW increases the circulating FVIII level by 2%. The aim of this study was to evaluate the impact of several morphometric parameters (BW, body mass index (BMI)-for-age, height), age and type of FVIII concentrate on FVIII recovery in children with HA. A total of 66 children aged between 10 and 18 with severe HA selected from six pharmacokinetic (PK) clinical trials using two recombinant FVIII concentrates were included in the analysis. Regression tree (RT) was used to identify predictors of FVIII recovery. The median age was 14.5 years with a median FVIII recovery of 2.09 for all children. The median FVIII recovery was not significantly different between age groups. Two groups were created by RT: children with a BMI-for-age percentile

  12. Galectin-1 and Galectin-3 Constitute Novel-Binding Partners for Factor VIII. (United States)

    O'Sullivan, Jamie M; Jenkins, P Vince; Rawley, Orla; Gegenbauer, Kristina; Chion, Alain; Lavin, Michelle; Byrne, Barry; O'Kennedy, Richard; Preston, Roger J S; Brophy, Teresa M; O'Donnell, James S


    Recent studies have demonstrated that galectin-1 (Gal-1) and galectin-3 (Gal-3) can bind von Willebrand factor and directly modulate von Willebrand factor-dependent early thrombus formation in vivo. Because the glycans expressed on human factor VIII (FVIII) are similar to those of von Willebrand factor, we investigated whether galectins might also bind and modulate the activity of FVIII. Immunosorbant assays and surface plasmon resonance analysis confirmed that Gal-1 and Gal-3 bound purified FVIII with high affinity. Exoglycosidase removal of FVIII N-linked glycans significantly reduced binding to both Gal-1 and Gal-3. Moreover, combined removal of both the N- and O-glycans of FVIII further attenuated Gal-3 binding. Notably, specific digestion of FVIII high-mannose glycans at N239 and N2118 significantly impaired FVIII affinity for Gal-1. Importantly Gal-1, but not Gal-3, bound to free FVIII in the plasma milieu, and significantly inhibited FVIII functional activity. Interestingly, commercial recombinant FVIII (rFVIII) concentrates are manufactured in different cell lines and differ in their glycosylation profiles. Although the biological mechanism has not been defined, recent studies in previously untreated patients with severe hemophilia A reported significant differences in inhibitor development associated with different rFVIII products. Interestingly, Gal-1 and Gal-3 both displayed enhanced affinity for BHK-rFVIII compared with CHO-rFVIII. Furthermore, binding of Gal-1 and Gal-3 to BDD-FVIII was markedly reduced compared with full-length rFVIII. We have identified Gal-1 and Gal-3 as novel-binding partners for human FVIII and demonstrated that Gal-1 binding can influence the procoagulant activity of FVIII. © 2016 American Heart Association, Inc.

  13. Pharmacokinetic properties of BAY 81-8973, a full-length recombinant factor VIII. (United States)

    Shah, A; Delesen, H; Garger, S; Lalezari, S


    BAY 81-8973 is a full-length recombinant factor VIII (FVIII) with the same primary amino acid sequence as sucrose-formulated recombinant FVIII (rFVIII-FS) but is produced with advanced manufacturing technologies. To analyse the pharmacokinetics (PK) of BAY 81-8973 after single and multiple dosing across different age and ethnic groups in the LEOPOLD clinical trial programme. The LEOPOLD trials enrolled patients with severe haemophilia A aged 12-65 years (LEOPOLD I and II) or ≤12 years (LEOPOLD Kids) with ≥150 (LEOPOLD I and II) or ≥50 (LEOPOLD Kids) exposure days to any FVIII product and no history of FVIII inhibitors. PK were assessed using chromogenic and one-stage assays (only chromogenic assay for LEOPOLD Kids) after a single 50-IU kg(-1) dose of BAY 81-8973 and, in a subset of patients in LEOPOLD I, after repeated dosing. Pharmacokinetic analyses were also performed based on age (18 to 65, 12 to <18, 6 to <12 and <6 years) and ethnicity (Asian and non-Asian). Pharmacokinetic assessments in the LEOPOLD I trial showed non-inferiority of BAY 81-8973 vs. rFVIII-FS. The PK of BAY 81-8973 were comparable after single and multiple dosing. Age-based analysis in the three trials showed that plasma concentrations were slightly lower for children, but similar for adolescents compared with adults. Pharmacokinetic results were similar in the different ethnic groups. Results of the LEOPOLD trials show that the BAY 81-8973 pharmacokinetic profile is non-inferior to rFVIII-FS. Similar BAY 81-8973 pharmacokinetic values were observed following single and repeated dosing and across ethnic groups. © 2015 John Wiley & Sons Ltd.

  14. Strategies for improving extracellular lipolytic enzyme production by Thermus thermophilus HB27. (United States)

    Deive, Francisco J; Carvalho, Elisabete; Pastrana, Lorenzo; Rúa, Maria L; Longo, Maria A; Sanroman, M Angeles


    In Thermus thermophilus HB27 cultures the localisation of lipolytic activity is extracellular, intracellular and membrane bound, with low percentage for the former. Therefore, the extracellular secretion must be increased in order to simplify the downstream process and to reduce the economic cost. This study focuses on the design of an innovative operational strategy to increase extracellular lipolytic enzyme production by T. thermophilus HB27 at bioreactor scale. In order to favour its secretion, the effect of several operational variables was evaluated. Among them, the presence of oils in the culture medium leads to improvements in growth and lipolytic enzyme activity. Sunflower oil is the most efficient inducer showing better results when added after 10h of growth. On the other hand, although surfactants lead to an almost complete inhibition of growth and lipolytic enzyme production, their addition along the culture could affect the location of the enzyme. Thus, by addition of surfactants at the stationary phase, a release of intracellular and membrane enzyme which increases the extracellular enzyme proportion is detected. Based on these results, strategies with successive addition of oil and surfactant in several culture phases in shake flask are developed and verified in a laboratory scale stirred tank bioreactor.

  15. At high altitude in the Netherlands: secondary erythrocytosis due to HB-Malmö (United States)

    Santbergen, Bart; van der Heul, Cees


    We describe two patients, a father and a son, presenting with erythrocytosis. Evaluation showed no pulmonal or cardial disorders. Owing to an elevated erythropoietin level after phlebotomy, a physiological secondary polycythaemia was suspected. A haemoglobin electrophoresis showed that our patients have a haemoglobinopathy with high affinity for oxygen, called Hb-Malmö (exon 3: c.294 C>G p.His98Gln). Hb-Malmö is a congenital disorder located on a gene at chromosome 11, in the B-chain on codon 97, decoding the α-subunit and β-subunit of the haemoglobin. Through a mutation (CAC→CAG), histidine is replaced by glutamine. The mutation causes a disorder in the connection between the α1-subunit and β2-subunit of the haemoglobin structure. These connections are important sites for binding oxygen. Mutated haemoglobin has a preference for an oxygenated status, which implicates that there is an increased binding and decreased release of oxygen. To compensate, there will be an erythrocytosis to transport sufficient oxygen to the peripheral tissues. PMID:24599433

  16. Genomic characterization of Pasteurella multocida HB01, a serotype A bovine isolate from China. (United States)

    Peng, Zhong; Liang, Wan; Liu, Wenjing; Wu, Bin; Tang, Biao; Tan, Chen; Zhou, Rui; Chen, Huanchun


    Pasteurella multocida infects various domestic and feral animals, generally causing clinical disease. To investigate P. multocida disease in cattle, we sequenced the complete genome of P. multocida HB01 (GenBank accession CP006976), a serotype A organism isolated from a cow in China. The genome is composed of a single circular chromosome of 2,416,068 base pairs containing 2212 protein-coding sequences, 6 ribosomal rRNA operons, and 56 tRNA genes. The present study confirms that P. multocida HB01 possesses a more complete metabolic pathway with an intact trichloroacetic acid cycle for anabolism compared with A. pleuropneumoniae and Haemophilus parasuis. This is the first time that this metabolic mechanism of P. multocida has been described. We also identified a full spectrum of genes related to known virulence factors of P. multocida. The differences in virulence factors between strains of different serotypes and origins were also compared. This comprehensive comparative genome analysis will help in further studies of the metabolic pathways, genetic basis of serotype, and virulence of P. multocida. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Features of the electronic structure of the active center of an HbS molecule (United States)

    Novoselov, D. Yu.; Korotin, Dm. M.; Anisimov, V. I.


    Features of the electronic structure of the nonprotein part of the mutant form of the human hemoglobin molecule, HbS, are studied along with the magnetic state of the iron ion that is the "nucleus" of the active center of the molecule. It is found that the mutant form of the HbS molecule differs from a normal hemoglobin molecule by the distortion of the local environment of the iron ion, which changes the energy level splitting by a crystal field. As a result of ab initio calculations, the magnetic transition in the iron atom from the high-spin state to the low-spin state upon the addition of molecular oxygen to hemoglobin molecule is reproduced. It is established for the first time that a change in the crystal and electronic structure of the active center as a result of a mutation can lead to a substantial change in the energy of the bond between the active center of the hemoglobin molecule and an oxygen molecule.

  18. Development of pro-inflammatory phenotype in monocytes after engulfing Hb-activated platelets in hemolytic disorders. (United States)

    Singhal, Rashi; Chawla, Sheetal; Rathore, Deepak K; Bhasym, Angika; Annarapu, Gowtham K; Sharma, Vandana; Seth, Tulika; Guchhait, Prasenjit


    Monocytes and macrophage combat infections and maintain homeostatic balance by engulfing microbes and apoptotic cells, and releasing inflammatory cytokines. Studies have described that these cells develop anti-inflammatory properties upon recycling the free-hemoglobin (Hb) in hemolytic conditions. While investigating the phenotype of monocytes in two hemolytic disorders-paroxysmal nocturnal hemoglobinuria (PNH) and sickle cell disease (SCD), we observed a high number of pro-inflammatory (CD14(+)CD16(hi)) monocytes in these patients. We further investigated in vitro the phenotype of these monocytes and found an estimated 55% of CD14(+) cells were transformed into the CD14(+)CD16(hi) subset after engulfing Hb-activated platelets. The CD14(+)CD16(hi) monocytes, which were positive for both intracellular Hb and CD42b (platelet marker), secreted significant amounts of TNF-α and IL-1β, unlike monocytes treated with only free Hb, which secreted more IL-10. We have shown recently the presence of a high number of Hb-bound hyperactive platelets in patients with both diseases, and further investigated if the monocytes engulfed these activated platelets in vivo. As expected, we found 95% of CD14(+)CD16(hi) monocytes with both intracellular Hb and CD42b in both diseases, and they expressed high TNF-α. Furthermore our data showed that these monocytes whether from patients or developed in vitro after treatment with Hb-activated platelets, secreted significant amounts of tissue factor. Besides, these CD14(+)CD16(hi) monocytes displayed significantly decreased phagocytosis of E. coli. Our study therefore suggests that this alteration of monocyte phenotype may play a role in the increased propensity to pro-inflammatory/coagulant complications observed in these hemolytic disorders-PNH and SCD. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Using the likelihood ratio to evaluate allowable total error--an example with glycated hemoglobin (HbA1c). (United States)

    Åsberg, Arne; Odsæter, Ingrid Hov; Carlsen, Sven Magnus; Mikkelsen, Gustav


    Allowable total error is derived in many ways, often from data on biological variation in normal individuals. We present a new principle for evaluating allowable total error: What are the diagnostic consequences of allowable total errors in terms of errors in likelihood ratio (LR)? Glycated hemoglobin A1c in blood (HbA1c) in diagnosing diabetes mellitus is used as an example. Allowable total error for HbA1c is 3.0% derived from data on biological variation compared to 6.0% as defined by National Glycohemoglobin Standardization Program (NGSP). We estimated a function for LR of HbA1c in diagnosing diabetes mellitus using logistic regression with a clinical database (n=572) where diabetes status was defined by WHO criteria. Then we estimated errors in LR that correspond to errors in the measurement of HbA1c. Measuring HbA1c 3% too low at HbA1c of 6.5 percentage points (the suggested diagnostic limit) gives a LR of 0.36 times the correct LR, while measuring HbA1c 3% too high gives a LR of 2.77 times the correct LR. The corresponding errors in LR for allowable total error of 6% are 0.13 and 7.69 times the correct LR, respectively. These principles of evaluating allowable total error can be applied to any diagnostically used analyte where the distribution of the analyte's concentration is known in patients with and without the disease in a clinically relevant population. In the example used, the allowable total error of 6% leads to very erroneous LRs, suggesting that the NGSP limits of ±6% are too liberal.

  20. Accuracy and clinical utility of a point-of-care HbA1c testing device. (United States)

    Knaebel, Jennifer; Irvin, Benjamin R; Xie, Charles Z


    Point-of-care testing (POCT) is widely used to measure blood glucose levels in people with diabetes, although its use in measuring glycated hemoglobin (HbA1c) levels is less common, perhaps due to perceived performance issues and access to the technology. Forty blood samples were analyzed in duplicate using Bayer's A1CNow + ® Multi-Test A1C system (A1CNow + ) with 3 different reagent lots; HbA1c levels of the samples spanned the clinically relevant range of 4% to 10%. Corresponding samples were sent to a National Glycohemoglobin Standardization Program (NGSP) secondary reference laboratory (University of Missouri Secondary Reference Laboratory #9), which analyzed the samples with a Tosoh Automated Glycohemoglobin Analyzer HLC-723G8 (Tosoh G8; Tosoh Bioscience, Inc). Glycated hemoglobin levels measured with the A1CNow + aligned with measurements obtained using the laboratory method, with correlation coefficients of 0.985, 0.987, and 0.989 for the 3 lots, respectively. The 95% CIs for the differences between the A1CNow + levels and the mean HbA1c levels were within -0.55% to +0.50% for the 3 reagent lots, which is well within the currently acceptable limits of ±0.75% HbA1c required by the NGSP. Results were further analyzed per the new tighter NGSP performance criteria effective September 1, 2012, requiring that 37 of 40 results be within ±7% (relative bias) of the NGSP reference laboratory measures. All 3 lots met the tighter NGSP criteria. The A1CNow + provides accuracy and precision when performing POCT of HbA1c as an aid in diabetes management. Ongoing improvements in this and other HbA1c POCT devices may lead to a greater global acceptance of the role of POCT of HbA1c in diabetes management.

  1. RhHB1 mediates the antagonism of gibberellins to ABA and ethylene during rose (Rosa hybrida) petal senescence. (United States)

    Lü, Peitao; Zhang, Changqing; Liu, Jitao; Liu, Xiaowei; Jiang, Guimei; Jiang, Xinqiang; Khan, Muhammad Ali; Wang, Liangsheng; Hong, Bo; Gao, Junping


    Rose (Rosa hybrida) is one of the most important ornamental plants worldwide; however, senescence of its petals terminates the ornamental value of the flower, resulting in major economic loss. It is known that the hormones abscisic acid (ABA) and ethylene promote petal senescence, while gibberellins (GAs) delay the process. However, the molecular mechanisms underlying the antagonistic effects amongst plant hormones during petal senescence are still unclear. Here we isolated RhHB1, a homeodomain-leucine zipper I transcription factor gene, from rose flowers. Quantitative RT-PCR and GUS reporter analyses showed that RhHB1 was strongly expressed in senescing petals, and its expression was induced by ABA or ethylene in petals. ABA or ethylene treatment clearly accelerated rose petal senescence, while application of the gibberellin GA3 delayed the process. However, silencing of RhHB1 delayed the ABA- or ethylene-mediated senescence, and resulted in higher petal anthocyanin levels and lower expression of RhSAG12. Moreover, treatment with paclobutrazol, an inhibitor of GA biosynthesis, repressed these delays. In addition, silencing of RhHB1 blocked the ABA- or ethylene-induced reduction in expression of the GA20 oxidase encoded by RhGA20ox1, a gene in the GA biosynthetic pathway. Furthermore, RhHB1 directly binds to the RhGA20ox1 promoter, and silencing of RhGA20ox1 promoted petal senescence. Eight senescence-related genes showed substantial differences in expression in petals after treatment with GA3 or paclobutrazol. These results suggest that RhHB1 mediates the antagonistic effect of GAs on ABA and ethylene during rose petal senescence, and that the promotion of petal senescence by ABA or ethylene operates through an RhHB1-RhGA20ox1 regulatory checkpoint. © 2014 The Authors The Plant Journal © 2014 John Wiley & Sons Ltd.


    Directory of Open Access Journals (Sweden)

    Mutthofiyah Mutthofiyah


    Full Text Available Penelitian ini bertujuan untukmeningkatkan aktivitas belajar siswa dengan menggunakan metode group investigation (GI pada pokok bahasan pasar pada penelitian ini menggunakan penelitian tindakan kelas (PTK. Dalam penelitian ini dirancang menggunakan siklus, masing-masing siklus dengan tahapan perencanaan, pelaksanaan tindakan, observasi dan refleksi. Teknik pengumpulan data pada penelitian ini adalah dokumentasi, observasi dan tes.Hasil penelitian menunjukkan melalui meningkatkan metode group investigation (GI aktivitas siswa SMP 5 Kudus ada peningkatan yang sigifikan, dari siklus I kelas VIII F 15,8 (41,62% meningkat di siklus II menjadi 24,8 (72,9%, sedangkan di kelas VIII G siklus I 18,5 (47,04% meningkat menjadi 26,2 (74,7%; melalui penerapan metode group investigation hasil belajar siswa SMP 5 kudus meningkat sangat signifkan, ketuntasan belajar secara klasikal dari kelas VIII F pra siklus sebesar 17,64% terjadi peningkatan 47% ke siklus I dan meningkat menjadi 82,35% di siklus II. Sedangkan di kelas VII G pra siklus sebesar 22,85% meningkat 54,28% di siklus I dan meningkat menjadi 94,28% di siklus II. Saran yang peneliti berikan adalah sebagai berikut:1Kepada para guru diharapkan dapat menerapkan pembelajaran kooperatif khususnya pembelajaran kooperatif tipe Group Investigation (GI dalam proses pembelajaran ekonomi dan mata pelajaran lainya dan mengembangkannya; 2 Kepada para peneliti selanjutnya diharapkan dapat melakukan penelitian tentang penerapan model pembelajaran yang dapat membangkitkan keaktifan siswa untuk belajar ekonomi. This study aims to improve students' learning activities using group investigation (GI on the subject of markets in class VIII SMP 5 Kudus. In this study is designed to use cycles, with each cycle stages of planning, action, observation and reflection. Data collection techniques in this study is documentation, observation and tests. Results showed through improved methods of group investigation (GI junior 5 high

  3. Development of a reliable analytical method for the precise extractive spectrophotometric determination of osmium(VIII) with 2-nitrobenzaldehydethiocarbohydrazone: Analysis of alloys and real sample (United States)

    Zanje, Sunil B.; Kokare, Arjun N.; Suryavanshi, Vishal J.; Waghmode, Duryodhan P.; Joshi, Sunil S.; Anuse, Mansing A.


    The proposed method demonstrates that the osmium(VIII) forms complex with 2-NBATCH from 0.8 mol L- 1 HCl at room temperature. The complex formed was extracted in 10 mL of chloroform with a 5 min equilibration time. The absorbance of the red colored complex was measured at 440 nm against the reagent blank. The Beer's law was obeyed in the range of 5-25 μg mL- 1, the optimum concentration range was 10-20 μg mL- 1 of osmium(VIII) as evaluated by Ringbom's plot. Molar absorptivity and Sandell's sensitivity of osmium(VIII)-2NBATCH complex in chloroform is 8.94 × 103 L mol- 1 cm- 1 and 0.021 μg cm- 2, respectively. The composition of osmium(VIII)-2NBATCH complex was 1:2 investigated from Job's method of continuous variation, Mole ratio method and slope ratio method. The interference of diverse ions was studied and masking agents were used wherever necessary. The present method was successfully applied for determination of osmium(VIII) from binary, ternary and synthetic mixtures corresponding to alloys and real samples. The validity of the method was confirmed by finding the relative standard deviation for five determinations which was 0.29%.

  4. Combined X-ray and neutron diffraction study of vacancies and disorder in the dimorphic clathrate Ba8Ga16Sn30 of type I and VIII. (United States)

    Christensen, Sebastian; Avila, Marcos A; Suekuni, Koichiro; Piltz, Ross; Takabatake, Toshiro; Christensen, Mogens


    We report detailed structural investigations of the dimorphic clathrate Ba8Ga16Sn30 that crystallizes in both type I and VIII clathrate structures. Single crystals of type I and VIII have been examined using single crystal X-ray and Laue neutron diffraction in the temperature range T = 10 K-500 K. The utilization of both X-ray and neutron diffraction gives a unique ability to reveal the occurrence of minute vacancy occupancies in the host structure. The vacancies are shown to be located on the 6c (type I) and 24g (type VIII) framework sites. Largest vacancy densities are observed for type I p-Ba8Ga16Sn30, 1.3(4)%, and type VIII n-Ba8Ga16Sn30, 0.7(2)%. The relation between guest atom disorder and occurrence of glasslike thermal conductivity in intermetallic clathrates was also investigated. In type VIII Ba8Ga16Sn30 neither n-type (crystalline thermal conductivity) nor p-type (glasslike thermal conductivity) showed any significant disorder of the guest atoms; they do however show anharmonic motion. The glasslike thermal conductivity of p-type Ba8Ga16Sn30 is interpretable as a result of higher effective mass of p-type charge-carriers affecting phonon scattering. In type I Ba8Ga16Sn30 guest atoms are highly disordered for both carrier types and samples of both charge carrier types have glasslike thermal conductivity.

  5. Successful immune tolerance induction consisting of high-dose factor VIII rich in von Willebrand factor and pulsed intravenous immunoglobulin: a case report

    Directory of Open Access Journals (Sweden)

    Kubisz Peter


    Full Text Available Abstract Introduction The development of factor VIII inhibitors is a serious complication of replacement therapy in patients with congenital hemophilia A. Immune tolerance induction has been accepted as the only clinically proven treatment allowing antigen-specific tolerance to factor VIII. However, some of its issues, such as patient selection, timing, factor VIII dosing, use of immunosuppressive or immunomodulatory procedures, still remain the subject of debate. Case presentation A case of a 3-year-old Caucasian boy with severe congenital hemophilia A, intron 22 inversion of the F8 gene and high-titer inhibitor, who underwent an immune tolerance induction according to the modified Bonn regimen (high doses of plasma-derived factor VIII rich in von Willebrand factor and pulsed intravenous immunoglobulin is presented. The treatment lasted for 13 months and led to the eradication of inhibitor. Conclusion Addition of intravenous immunoglobulin did not negatively affect the course of immune tolerance induction and led to the rapid eradication of factor VIII inhibitor.

  6. The Effect of Growth Temperature and V/III Flux Ratio of MOCVD Antimony Based Semiconductors on Growth Rate and Surface Morphology

    Directory of Open Access Journals (Sweden)

    Ramelan Ari Handono


    Full Text Available Epitaxial Alx Ga1-x Sb layers on GaSb and GaAs substrates have been grown by atmospheric pressure metalorganic chemical vapor deposition using TMAl, TMGa and TMSb. Nomarski microscope and a profiler were employed to examine the surface morphology and growth rate of the samples. We report the effect of growth temperature and V/III flux ratio on growth rate and surface morphology. Growth temperatures in the range of 520°C and 680°C and V/III ratios from 1 to 5 have been investigated. A growth rate activation energy of 0.73 eV was found. At low growth temperatures between 520 and 540°C, the surface morphology is poor due to antimonide precipitates associated with incomplete decomposition of the TMSb. For layers grown on GaAs at 580°C and 600°C with a V/III ratio of 3 a high quality surface morphology is typical, with a mirror-like surface and good composition control. It was found that a suitable growth temperature and V/III flux ratio was beneficial for producing good AlGaSb layers. Undoped AlGaSb grown at 580°C with a V/III flux ratio of 3 at the rate of 3.5 μm/hour shows p-type conductivity with smooth surface morphology

  7. Effect of V/III ratio on the surface morphology and electrical properties of m-plane (10 1 bar 0) GaN homoepitaxial layers (United States)

    Barry, Ousmane I.; Tanaka, Atsushi; Nagamatsu, Kentaro; Bae, Si-Young; Lekhal, Kaddour; Matsushita, Junya; Deki, Manato; Nitta, Shugo; Honda, Yoshio; Amano, Hiroshi


    We have investigated the effect of V/III ratio on the surface morphology, impurity concentration and electrical properties of m-plane (10 1 bar 0) Gallium Nitride (GaN) homoepitaxial layers. Four-sided pyramidal hillocks are observed on the nominally on-axis m-plane GaN films. Hillocks sizes relatively increase by increasing the V/III ratio. All facets of pyramidal hillocks exhibit well-defined step-terrace features. Secondary ion mass spectrometry depth profiles reveal that carbon impurities decrease by increasing the V/III ratio while the lowest oxygen content is found at an optimized V/III ratio of 900. Vertical Schottky barrier diodes fabricated on the m-GaN samples were characterized. Low leakage current densities of the order of 10-10 A/cm2 at -5 V are obtained at the optimum V/III ratio. Oxygen impurities and screw-component dislocations around hillocks are found to have more detrimental impact on the leakage current mechanism.


    Directory of Open Access Journals (Sweden)



    Full Text Available Abstract: Pessimism and attitudes that consider themselves weak and does not have the ability when facing a problem will make individual impediment in the task of development. Problems confidence that underlies the research are: a Students are less confident in the ability it has, b Students feel pessimistic when faced with an issue, c Student perception subjectively, d Students still do not do the work independently, and e negative minded students with a state-owned. The problems of this study are whether there is an influence of information services using the medium of film to the confidence of eighth-grade students of SMP Negeri 8 Metro. The purpose of this study was to determine whether there is an influence of information services using the medium of film to the self-confidence of students in class VIII SMP Negeri 8 Metro. Subject participant is graders VIII-E total 30 students. Data were collected by questionnaire self-confidence and analyzed the data used is the t-test. The results of this study, shown by the difference in change scores of confidence from the pre-test and post-test of 17.1. Testing the hypothesis obtained calculation results thitung6,036> table = 1.699. The conclusion is that the information services implemented using the film medium can be a positive influence on self-esteem, especially students of class VIII. The advice given is to use the medium of film should be done intensively and more creative by BK teachers in giving information service. Keywords: Confidence, Service Information Using Media Film.

  9. Chronic cerebral hypoperfusion-induced impairment of Aβ clearance requires HB-EGF-dependent sequential activation of HIF1α and MMP9. (United States)

    Ashok, Anushruti; Rai, Nagendra Kumar; Raza, Waseem; Pandey, Rukmani; Bandyopadhyay, Sanghamitra


    Chronic cerebral hypoperfusion (CCH) manifests Alzheimer's Disease (AD) neuropathology, marked by increased amyloid beta (Aβ). Besides, hypoxia stimulates Heparin-binding EGF-like growth factor (HB-EGF) mRNA expression in the hippocampus. However, involvement of HB-EGF in CCH-induced Aβ pathology remains unidentified. Here, using Bilateral Common Carotid Artery Occlusion mouse model, we explored the mechanism of HB-EGF regulated Aβ induction in CCH. We found that HB-EGF inhibition suppressed, while exogenous-HB-EGF triggered hippocampal Aβ, proving HB-EGF-dependent Aβ increase. We also detected that HB-EGF affected the expression of primary Aβ transporters, receptor for advanced glycation end-products (RAGE) and lipoprotein receptor-related protein-1 (LRP-1), indicating impaired Aβ clearance across the blood-brain barrier (BBB). An HB-EGF-dependent loss in BBB integrity supported impaired Aβ clearance. The effect of HB-EGF on Amyloid Precursor Protein pathway was relatively insignificant, suggesting a lesser effect on Aβ generation. Delving into BBB disruption mechanism demonstrated HB-EGF-mediated stimulation of Matrix metalloprotease-9 (MMP9), which affected BBB via HB-EGF-ectodomain shedding and epidermal growth factor receptor activation. Examining the intersection of HB-EGF-regulated pathway and hypoxia revealed HB-EGF-dependent increase in transcription factor, Hypoxia-inducible factor-1alpha (HIF1α). Further, via binding to hypoxia-responsive elements in MMP9 gene, HIF1α stimulated MMP9 expression, and therefore appeared as a prominent intermediary in HB-EGF-induced BBB damage. Overall, our study reveals the essential role of HB-EGF in triggering CCH-mediated Aβ accumulation. The proposed mechanism involves an HB-EGF-dependent HIF1α increase, generating MMP9 that stimulates soluble-HB-EGF/EGFR-induced BBB disintegration. Consequently, CCH-mediated hippocampal RAGE and LRP-1 deregulation together with BBB damage impair Aβ transport and clearance

  10. Joint bleeds increase the inhibitor response to human factor VIII in a rat model of severe haemophilia A

    DEFF Research Database (Denmark)

    Löfgren, Karin Maria; Søndergaard, H.; Skov, Søren


    Introduction The most serious complication in haemophilia A (HA) replacement therapy with coagulation factor VIII (FVIII) is neutralizing antibodies, i.e. inhibitors. It has been hypothesized that danger signals generated during a bleed might have an adjuvant effect on the immune response to FVIII...... in on-demand treatment, increasing the inhibitor risk. Aim To compare the antibody response to treatment with recombinant human FVIII (rhFVIII) in relation to induced knee joint bleeds and treatment without concurrent bleeds in a HA rat model. Method HA rats were divided into two groups: one group (n...

  11. Recombinant factor VIII Fc fusion protein for the prevention and treatment of bleeding in children with severe hemophilia A. (United States)

    Young, G; Mahlangu, J; Kulkarni, R; Nolan, B; Liesner, R; Pasi, J; Barnes, C; Neelakantan, S; Gambino, G; Cristiano, L M; Pierce, G F; Allen, G


    Prophylactic factor replacement, which prevents hemarthroses and thereby reduces the musculoskeletal disease burden in children with hemophilia A, requires frequent intravenous infusions (three to four times weekly). Kids A-LONG was a phase 3 open-label study evaluating the safety, efficacy and pharmacokinetics of a longer-acting factor, recombinant factor VIII Fc fusion protein (rFVIIIFc), in previously treated children with severe hemophilia A (endogenous FVIII level of hemophilia A. © 2015 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.


    Energy Technology Data Exchange (ETDEWEB)

    Miller, Matthew J.; Bregman, Joel N., E-mail:, E-mail: [Department of Astronomy, University of Michigan, Ann Arbor, MI 48104 (United States)


    The Milky Way hosts a hot (≈2 × 10{sup 6} K), diffuse, gaseous halo based on detections of z = 0 O VII and O VIII absorption lines in quasar spectra and emission lines in blank-sky spectra. Here we improve constraints on the structure of the hot gas halo by fitting a radial model to a much larger sample of O VII and O VIII emission line measurements from XMM-Newton/EPIC-MOS spectra compared to previous studies (≈650 sightlines). We assume a modified β-model for the halo density distribution and a constant-density Local Bubble from which we calculate emission to compare with the observations. We find an acceptable fit to the O VIII emission line observations with χ{sub red}{sup 2} (dof) = 1.08 (644) for best-fit parameters of n{sub o}r{sub c}{sup 3β}=1.35±0.24 cm{sup –3} kpc{sup 3β} and β = 0.50 ± 0.03 for the hot gas halo and negligible Local Bubble contribution. The O VII observations yield an unacceptable χ{sub red}{sup 2} (dof) = 4.69 (645) for similar best-fit parameters, which is likely due to temperature or density variations in the Local Bubble. The O VIII fitting results imply hot gas masses of M(<50 kpc) = 3.8{sub −0.3}{sup +0.3}×10{sup 9} M{sub ⊙} and M(<250 kpc) = 4.3{sub −0.8}{sup +0.9}×10{sup 10} M{sub ⊙}, accounting for ≲50% of the Milky Way's missing baryons. We also explore our results in the context of optical depth effects in the halo gas, the halo gas cooling properties, temperature and entropy gradients in the halo gas, and the gas metallicity distribution. The combination of absorption and emission line analyses implies a sub-solar gas metallicity that decreases with radius, but that also must be ≥0.3 Z {sub ☉} to be consistent with the pulsar dispersion measure toward the Large Magellanic Cloud.

  13. Conversaciones en el VIII Congreso Panamericano de Mecánica de Suelos e Ingeniería de Fundaciones


    Ruiz Restrepo, Carlos Enrique


    En el mes de agosto de 1987 se cumplió, en Cartagena de Indias el "VIII Congreso Panamericano de Mecánica de Suelos", bajo la presidencia del geólogo colombiano Juan Montero Olarte, asistido por un Comité Organizador de todas las excelencias. Abrir canales para la comunicación permanente entre todos nuestros centros educativos, o entre los más representativos, es el método más simple para garantizar, como en simbólico vaso comunicante, que el nivel de enseñanza vibre en un clima de con...

  14. Seleucid, Demotic and Mediterranean mathematics versus Chapters VIII and IX of the Nine Chapters: accidental or significant similarities?

    DEFF Research Database (Denmark)

    Høyrup, Jens

    Similarities of geometrical diagrams and arithmetical structures of problems have often been taken as evidence of transmission of mathematical knowledge or techniques between China and “the West”. Confronting on one hand some problems from Chapter VIII of the Nine Chapters with comparable problems...... known from Ancient Greek sources, on the other a Seleucid collection of problems about rectangles with a subset of the triangle problems from Chapter IX, it is concluded, (1) that transmission of some arithmetical riddles without method – not “from Greece” but from a transnational community of traders...

  15. Love and/in psychoanalysis: a commentary on Lacan's reading of Plato's Symposium in Seminar VIII: Transference. (United States)

    Fink, Bruce


    What is love and what part does it play in psychoanalysis? Where are the analyst and the analysand situated in relation to the roles defined as those of the "lover" and the "beloved"? Jacques Lacan explores these and other questions in his soon-to-be-published Seminar VIII: Transference by providing an extensive commentary on Plato's most famous dialogue on love, the Symposium. This paper outlines some of the major points about love that grow out of Lacan's reading of the dialogue and examines their relevance to the analytic setting. Can the analyst be characterized as a sort of modern-day Socrates?

  16. EK(b)P Keskkomitee VIII pleenumi stenogramm / tõlk. Mart Arold, tõlk. Jaan Isotamm

    Index Scriptorium Estoniae


    EK(b)P Keskkomitee VIII pleenum, 21.-23. märts 1950. Sõnavõtud: N. Karotamm, P. Ponomarenko, I. Käbin, V. Kuusik, A. Jaanus, V. Hiznjakov, E. Ristimägi, I. Suija, H. Ajo, A. Meri, G. Abels, M. Assin, G. Latõshov, Rumjantsev, Müürisepp. Kommenteerinud Viktor Niitsoo. Algus: Akadeemia (1998) nr. 12, lk. 2655-2683 ; Järg nr.2;3;4;5;6;7;8;9;10 lk.415-446;639-670;863-894;1087-1118;1310-1342;1534-1566;1759-1790;2017-2048;2220-2256

  17. Hb I-Toulouse in association with homozygosity for the α3.7 deletion in a Pacific Island woman

    Directory of Open Access Journals (Sweden)

    Beverley Pullon


    Full Text Available Only four cases of Hb I-Toulouse have been reported to date. Current literature associates Hb I-Toulouse in the heterozygote with a mild chronic hemolytic anemia. The variant is mildly unstable with a tendency to form metHb. The quantity of the variant in heterozygotes has been reported as varying between 33 to 40%. This report confirms the finding from a single case, that a reduced percentage of Hb IToulouse along with microcytosis can be attributed to the co-inheritance of an abnormal α globin genotype. This current case was found in a woman of Pacific People ethnicity residing in New Zealand. There is a high prevalence of α thalassemia in this ethnic group and New Zealand has the highest Pacific population in the world. Therefore, if a reduced percentage of Hb I-Toulouse is found with microcytosis and normal iron studies, co-inheritance with α thalassemia should be considered. 目前仅有四例Hb I-Toulouse的病例报告。 当前的文献将杂合子中的Hb I-Toulouse与慢性溶血性贫血相关联。 这种变异体轻度不稳定,有形成高铁血红蛋白(metHb)的倾向。 杂合子中变异体数量据报道为33%至40%不等。 本报告证实从单一病例得到的结果,即伴有小红细胞症的更低Hb I-Toulouse百分比可被归结为异常α球蛋白基因型的合并遗传。 该例当前病例在一名居住在新西兰的太平洋诸岛族裔女性身上发现。 在这个族群中存在较高的α地中海贫血患病率,而在全世界新西兰的太平洋诸岛族裔人口最多。 因此,如果发现Hb I-Toulouse的百分比更低,同时伴有小红细胞症并且检查铁含量正常,则应考虑α地中海贫血的合并遗传。

  18. Features of glycemic variations in drug naïve type 2 diabetic patients with different HbA1c values. (United States)

    Li, Feng-Fei; Liu, Bing-Li; Yan, Reng-Na; Zhu, Hong-Hong; Zhou, Pei-Hua; Li, Hui-Qin; Su, Xiao-Fei; Wu, Jin-Dan; Zhang, Dan-Feng; Ye, Lei; Ma, Jian-Hua


    To define the features of glycemic variations in drug naïve type 2 diabetic (T2D) patients with different HbA1c values using continuous glucose monitoring (CGM), a total of 195 drug naïve T2D patients were admitted. The subjects were divided into the following groups: lower HbA1c values (≤8%), moderate HbA1c values (>8% and ≤10%), and higher HbA1c values (>10%). The patients underwent oral glucose tolerance tests and were then subjected to 3-day CGM. The primary endpoint was the differences in the 24-hr mean amplitude of glycemic excursions (MAGE) in patients with different HbA1c values. Patients with higher HbA1c values had larger MAGEs than those in the moderate and lower groups (7.44 ± 3.00 vs. 6.30 ± 2.38, P values. Moreover, the patients with higher HbA1c values exhibited higher peak glucose concentrations and prolongation in the time to peak glucose. Patients with higher HbA1c values had larger MAGE compared with those with lower and moderate HbA1c values. Our data indicated patients with higher HbA1c values should receive special therapy aimed at reducing the larger glycemic variations.

  19. Simple diagnosis of HbA1c using the dual-plasmonic platform integrated with LSPR and SERS (United States)

    Heo, Nam Su; Kwak, Cheol Hwan; Lee, Hoomin; Kim, Dongjoo; Lee, Sunmook; Kim, Gi-bum; Kwon, Soonjo; Kim, Woo Sik; Huh, Yun Suk


    A plasmonic active chip was designed with a transparent polymer film self-assembled with gold nanoparticles (AuNPs). In this study, we demonstrated the feasibility and sensitivity of biosensors by employing a plasmonic resonance technique. AuNPs are widely used as biosensing probes because they facilitate stable immobilization of biomolecules. Transparent polymer film facilitated measurement of changes in absorbance via transmitted light and analysis of Raman scattering via scattered light. The cysteine rich protein G and anti-HbA1c were sequentially conjugated to self-assembled AuNPs on the transparent polymer film to detect a target protein. HbA1c, which is used as an indicator for diabetes diagnosis, was selected for target protein detection. We confirmed the linearly increased absorbance values with increasing HbA1c level (3.19-14.0%) by LSPR detection. We also verified the linear increase in SERS intensity as the concentration of anti-Hb increased from 10 ng mL-1 to 1 μg mL-1 by analyzing the SERS spectra of Cy3 labeled anti-Hb added substrates.

  20. Heparin-Binding EGF-like Growth Factor (HB-EGF) Therapy for Intestinal Injury: Application and Future Prospects (United States)

    Yang, Jixin; Su, Yanwei; Zhou, Yu; Besner, Gail E.


    Throughout the past 20 years, we have been investigating the potential therapeutic roles of heparin-binding EGF-like growth factor (HB-EGF), a member of the epidermal growth factor family, in various models of intestinal injury including necrotizing enterocolitis (NEC), intestinal ischemia/reperfusion (I/R) injury, and hemorrhagic shock and resuscitation (HS/R). Our studies have demonstrated that HB-EGF acts as an effective mitogen, a restitution-inducing reagent, a cellular trophic factor, an anti-apoptotic protein and a vasodilator, via its effects on various cell types in the intestine. In the current paper, we have reviewed the application and therapeutic effects of HB-EGF in three classic animal models of intestinal injury, with particular emphasis on its protection of the intestines from NEC. Additionally, we have summarized the protective functions of HB-EGF on various target cells in the intestine. Lastly, we have provided a brief discussion focusing on the future development of HB-EGF clinical applications for the treatment of various forms of intestinal injury including NEC. PMID:24345808