Science.gov

Sample records for recombinante heberbiovac hb

  1. Novel permeability characteristics of red blood cells from sickle cell patients heterozygous for HbS and HbC (HbSC genotype).

    PubMed

    Dalibalta, S; Ellory, J C; Browning, J A; Wilkins, R J; Rees, D C; Gibson, J S

    2010-06-15

    Individuals heterozygous for HbS and HbC (HbSC) represent about 1/3(rd) of sickle cell disease (SCD) patients. Whilst HbSC disease is generally milder, there is considerable overlap in symptoms with HbSS disease. HbSC patients, as well as HbSS ones, present with the chronic anaemia and panoply of acute vaso-occlusive complications that characterize SCD. However, there are important clinical and haematological differences. Certain complications occur with greater frequency in HbSC patients (like proliferative retinopathy and osteonecrosis) whilst intravascular haemolysis is reduced. Patients with HbSC disease can be considered as a discrete subset of SCD cases. Although much work has been carried out on understanding the pathogenesis of SCD in HbSS homozygotes, including the contribution of altered red blood cell permeability, relatively little pertains directly to HbSC individuals. Results reported in the literature suggest that HbSC cells, and particularly certain subpopulations, present with similar permeability to HbSS cells but there are also important differences - these have not been well characterized. We hypothesise that their unique cell transport properties accounts for the different pattern of disease in HbSC patients and represents a potential chemotherapeutic target not shared in red blood cells from HbSS patients. The distinct pattern of clinical haematology in HbSC disease is emphasised here. We analyse some of the electrophysiological properties of single red blood cells from HbSC patients, comparing them with those from HbSS patients and normal HbAA individuals. We also use the isosmotic haemolysis technique to investigate the behaviour of total red blood cell populations. Whilst both HbSS and HbSC cells show increased monovalent and divalent (Ca(2+)) cation conductance further elevated upon deoxygenation, the distribution of current magnitudes differs, and outward rectification is greatest for HbSC cells. In addition, although Gd(3+) largely

  2. Stability study for magnetic reagent assaying Hb and HbA1c

    NASA Astrophysics Data System (ADS)

    Hsieh, Wen-Pin; Chieh, J. J.; Yang, C. C.; Yang, S. Y.; Chen, Po-Yu; Huang, Yu-Hao; Hong, Y. W.; Horng, H. E.

    2013-01-01

    Reagents for magnetically labeled immunoassay on human Hb and human HbA1c have been synthesized. The reagents consist of Fe3O4 magnetic particles biofunctionalized with antibodies against Hb and HbA1c. It has been demonstrated that the reagents can be applied to quantitatively detect Hb and HbA1c by using immunomagnetic reduction assay. In addition to characterizing the assay properties, such as the standard curve and the low-detection limit, the stability of reagents is investigated. To do this, the temporal dependence of particle sizes and the bio-activity of reagents are monitored. The results show that the reagents are highly stable when stored at 2-8 °C. This means that the reagents synthesized in this work are promising for practical applications.

  3. A rare hemoglobin variant, Hb Belliard

    PubMed Central

    Benavides, Raul

    2017-01-01

    There are many documented variants of hemoglobin; however, other than a limited number (such as sickle cell disease), very few are known to have any clinical significance. As advances in detection and identification continue through gel electrophoresis, capillary electrophoresis, and DNA sequencing, more rare variants are identified. Without case reporting, the significance of these variants will remain unknown or continue to be thought of as insignificant. Here we report a rare hemoglobin variant, Hb Belliard, which was detected in a 68-year-old Indian immigrant to the United States. He presented with elevated hemoglobin and was found to have a unique peak on capillary electrophoresis. The specimen was sent for sequencing and was subsequently found to have Hb Belliard. Currently, Hb Belliard is thought to be insignificant.

  4. Diagnosis of a rare double heterozygous Hb D Punjab/Hb Q India hemoglobinopathy using Sebia capillary zone electrophoresis.

    PubMed

    Parab, Sushama; Sakhare, Suhas; Sengupta, Caesar; Velumani, Arokiaswamy

    2014-01-01

    In India, hemoglobinopathies constitute a major genetic disorder and hemoglobin variants such as Hb S, Hb D Punjab, and Hb E are the most common ones. Other variants include Hb Q India, Hb Lepore, Hb J Meerut, Hb D Iran, etc. These variants show heterozygous state along with beta thalassemia. However, compound heterozygosities among these variants are very rare. Ethylenediaminetetraacetic acid whole blood sample received for routine thalassemia screening was subjected to alkaline electrophoresis using automated capillary zone electrophoresis. Suspecting the presence of rare variants, further analysis was carried out using Bio-Rad D10 and Tosoh G8 high-performance liquid chromatography (HPLC) systems. Capillary zone electrophoretograms showed the presence of peaks in zone Hb A, Hb D, a fused peak in Hb A2, and a small peak in Z1 zone. Bio-Rad and Tosoh chromatograms also indicated the presence of four peaks which are identified as Hb A, Hb D Punjab, Hb Q India, and hybrid of Hb D Punjab/Hb Q India. A peak in Hb D zone of capillary was due to co-migration of Hb D Punjab and Hb Q India variants. Small peak in Z1 zone indicated the presence of alpha chain variant Hb Q India. The findings were further confirmed by HPLC results and molecular genetic studies. The present study reports for the 1st time a rare hemoglobinopathy of double heterozygosity for Hb D Punjab, Hb Q India on Capillarys 2 Flex Piercing analyzer and is forth reported case for this rare hemoglobinopathy.

  5. Relationship between Hb and HbA1c in Japanese adults: an analysis of the 2009 Japan Society of Ningen Dock database.

    PubMed

    Takahashi, Eiko; Moriyama, Kengo; Yamakado, Minoru

    2014-06-01

    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.

  6. Cation Homeostasis in Red Cells From Patients With Sickle Cell Disease Heterologous for HbS and HbC (HbSC Genotype).

    PubMed

    Hannemann, A; Rees, D C; Tewari, S; Gibson, J S

    2015-11-01

    Sickle cell disease (SCD) in patients of HbSC genotype is considered similar, albeit milder, to that in homozygous HbSS individuals--but with little justification. In SCD, elevated red cell cation permeability is critical as increased solute loss causes dehydration and encourages sickling. Recently, we showed that the KCl cotransporter (KCC) activity in red cells from HbSC patients correlated significantly with disease severity, but that in HbSS patients did not. Two transporters involved in red cell dehydration, the conductive channels Psickle and the Gardos channel, behaved similarly in red cells from the two genotypes, but were significantly less active in HbSC patients. By contrast, KCC activity was quantitatively greater in HbSC red cells. Results suggest that KCC is likely to have greater involvement in red cell dehydration in HbSC patients, which could explain its association with disease severity in this genotype. This work supports the hypothesis that SCD in HbSC patients is a distinct disease entity to that in HbSS patients. Results suggest the possibility of designing specific treatments of particular benefit to HbSC patients and a rationale for the development of prognostic markers, to inform early treatment of children likely to develop more severe complications of the disease.

  7. Anti-human HB-EGF monoclonal antibodies inhibiting ectodomain shedding of HB-EGF and diphtheria toxin binding.

    PubMed

    Hamaoka, Miki; Chinen, Ichino; Murata, Takuya; Takashima, Seiji; Iwamoto, Ryo; Mekada, Eisuke

    2010-07-01

    HB-EGF is a member of the EGF family of growth factors that bind and activate the EGF receptor. HB-EGF is synthesized as a membrane-anchored protein (proHB-EGF), and then proteolytically cleaved, resulting in the mitogenically active soluble form. ProHB-EGF functions as the receptor for the diphtheria toxin (DT). HB-EGF plays pivotal roles in pathophysiological processes, including cancer. Monoclonal antibodies (mAbs) specific for HB-EGF could be an important tool in HB-EGF research. However, few such mAbs have been established to date. In this study, we newly generated seven clones of hybridoma-derived mAbs by immunizing HB-EGF null mice with recombinant human HB-EGF protein. All mAbs specifically bound to human HB-EGF but not to mouse HB-EGF. Epitope mapping analysis showed that most of the mAbs recognized the EGF-like domain. Although none of the newly isolated mAbs directly inhibited the mitogenic activity of HB-EGF for EGFR-expressing cells, some strongly inhibited DT-binding. Interestingly, some of the mAbs efficiently inhibited ectodomain shedding of proHB-EGF, and consequently prevented the cell growth of the EGFR-expressing cells in a co-culture system with proHB-EGF-expressing cells. Hence, these new anti-HB-EGF mAbs may advance clinical as well as basic research on HB-EGF.

  8. Poly(4-hydroxybutyrate) (P4HB) production in recombinant Escherichia coli: P4HB synthesis is uncoupled with cell growth

    PubMed Central

    2013-01-01

    Background Poly(4-hydroxybutyrate) (P4HB), belonging to the family of bacterial polyhydroxyalkanoates (PHAs), is a strong, flexible and absorbable material which has a large variety of medical applications like tissue engineering and drug delivery. For efficient production of P4HB recombinant Escherichia coli has been employed. It was previously found that the P4HB synthesis is co-related with the cell growth. In this study, we aimed to investigate the physiology of P4HB synthesis, and to reduce the total production cost by using cheap and widely available xylose as the growth substrate and sodium 4-hydroxybutyrate (Na-4HB) as the precursor for P4HB synthesis. Results Six different E. coli strains which are able to utilize xylose as carbon source were compared for their ability to accumulate P4HB. E. coli JM109 was found to be the best strain regarding the specific growth rate and the P4HB content. The effect of growth conditions such as temperature and physiological stage of Na-4HB addition on P4HB synthesis was also studied in E. coli JM109 recombinant in batch culture. Under the tested conditions, a cellular P4HB content in the range of 58 to 70% (w w-1) and P4HB concentrations in the range of 2.76 to 4.33 g L-1 were obtained with a conversion yield (YP4HB/Na-4HB) of 92% w w-1 in single stage batch cultures. Interestingly, three phases were identified during P4HB production: the “growth phase”, in which the cells grew exponentially, the “accumulation phase”, in which the exponential cell growth stopped while P4HB was accumulated exponentially, and the “stagnation phase”, in which the P4HB accumulation stopped and the total biomass remained constant. Conclusions P4HB synthesis was found to be separated from the cell growth, i.e. P4HB synthesis mainly took place after the end of the exponential cell growth. High conversion rate and P4HB contents from xylose and precursor were achieved here by simple batch culture, which was only possible previously

  9. Stress analysis of the HFIR HB-2 and HB-3 beam tube nozzles

    SciTech Connect

    Williams, P.T.

    1998-08-01

    The results of three-dimensional linear elastic stress analyses of the HFIR HB-2 and HB-3 nozzles are presented in this report. Finite element models were developed using the PATRAN pre-processing code and translated into ABAQUS input file format. A scoping analysis using simple geometries with internal pressure loading was carried out to assess the capabilities of the ABAQUS/Standard code to calculate maximum principal stress distributions within cylinders with and without holes. These scoping calculations were also used to provide estimates for the variation in tangential stress around the rim of a nozzle using the superposition of published closed-form solutions for the stress around a hole in an infinite flat plate under uniaxial tension. From the results of the detailed finite element models, peak stress concentration factors (based on the maximum principal stresses in tension) were calculated to be 3.0 for the HB-2 nozzle and 2.8 for the HB-3 nozzle. Submodels for each nozzle were built to calculate the maximum principal stress distribution in the weldment region around the nozzle, where displacement boundary conditions for the submodels were automatically calculated by ABAQUS using the results of the global nozzle models. Maximum principal stresses are plotted and tabulated for eight positions around each nozzle and nozzle weldment.

  10. [Evaluation of HbA1c using different methods in haemoglobin variant, Hb J-Bangkok].

    PubMed

    Sawaragi, Wakana; Shibuya, Hitoshi; Yasuda, Keiko; Suzuki, Haruki; Shimizu, Chikara; Matsuno, Kazuhiko

    2009-05-01

    A 31-year-old Japanese man with haemoglobin variant, Hb J-Bangkok [beta56 (D7) Gly-->Asp], was found by discrepant values between HbA1c and glycated-albumin. We measured HbA1c using three different methods, HPLC, enzyme assay and turbidimetric immunoassay. HbA1c value measured by HPLC was much lower than those by others. Furthermore, we estimated calculated glyco-haemoglobin value measured by high-resolution HPLC, revealing that HbA1c values measured by enzyme assay and turbidimetric immunoassay were comparable with calculated value. When measuring HbA1c value in haemoglobin variant, Hb J Bangkok, enzyme assay and turbidimetric immunoassay are useful methods.

  11. Phenotypic Diversity of Sickle Cell Disease in Patients with a Double Heterozygosity for Hb S and Hb D-Punjab.

    PubMed

    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

    2016-09-01

    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.

  12. The Hb F composition in a Moroccan family with beta zero-thalassaemia and Hb O-Arab.

    PubMed

    Morlé, F; Morlé, L; Baklouti, F; Dorléac, E; Baudonnet, C; Delaunay, J; Godet, J

    1984-09-01

    We report on a Moroccan family in which the proposita displays a picture of beta-thalassaemia intermedia, associated with heterozygous Hb O-Arab (beta 121 Glu----Lys) and a beta zero-thalassaemia trait. Hb O-Arab was ascertained by the disappearance of the Eco RI restriction site that normally overlaps the beta-globin gene codon 121. The proposita further presents high proportions of Hb F (12.1%) and of G gamma chains (68.6%). The transmission of the proband's haemoglobin markers was analyzed (the proband's husband displaying normal haemoglobin). The beta zero-thalassaemia and O-Arab genes underwent mutual exclusion. A high Hb F (9.28%) level was found in one child, in association with the beta zero-thalassaemia trait, while another child carrying the latter trait displayed normal levels of Hb F. This situation suggests that a heterocellular HPFH determinant is involved. However, there was no means to establish whether the high Hb F proportion in the mother results solely from the beta zero-thalassaemia -Hb O-Arab association or whether an additional HPFH determinant is present. No DNA deletion was detectably associated with the high proportion of Hb F. In this family, the G gamma percentage was high whenever the beta zero-thalassaemia gene was present, regardless of total Hb F percentage. This observation is consistent with the view that the control of the G gamma percentage in the adult is linked to the beta-locus.

  13. HbMADS4, a MADS-box Transcription Factor from Hevea brasiliensis, Negatively Regulates HbSRPP

    PubMed Central

    Li, Hui-Liang; Wei, Li-Ran; Guo, Dong; Wang, Ying; Zhu, Jia-Hong; Chen, Xiong-Ting; Peng, Shi-Qing

    2016-01-01

    In plants MADS-box transcription factors (TFs) play important roles in growth and development. However, no plant MADS-box gene has been identified to have a function related to secondary metabolites regulation. Here, a MADS-box TF gene, designated as HbMADS4, was isolated from Hevea brasiliensis by the yeast one-hybrid experiment to screen the latex cDNA library using the promoter of the gene encoding H. brasiliensis small rubber particle protein (HbSRPP) as bait. HbMADS4 was 984-bp containing 633-bp open reading frame encoding a deduced protein of 230 amino acid residues with a typical conserved MADS-box motif at the N terminus. HbMADS4 was preferentially expressed in the latex, but little expression was detected in the leaves, flowers, and roots. Its expression was inducible by methyl jasmonate and ethylene. Furthermore, transient over-expression and over-expression of HbMADS4 in transgenic tobacco plants significantly suppressed the activity of the HbSRP promoter. Altogether, it is proposed that HbMADS4 is a negative regulator of HbSRPP which participates in the biosynthesis of natural rubber. PMID:27895659

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

    SciTech Connect

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

    2008-10-31

    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/Ser{sub 108/121}, HB-EGF-Cys/Ser{sub 116/132}, and HB-EGF-Cys/Ser{sub 134/143}) was cloned under the regulation of the mouse metallothionein (MT) promoter and stably expressed in mouse fibroblasts. HB-EGF immunoreactive proteins with M{sub r} of 6.5, 21 and 24 kDa were observed from lysates of HB-EGF and each HB-EGF disulfide analogue. HB-EGF immunohistochemical analyses of each HB-EGF stable cell line demonstrated ubiquitous protein expression except HB-EGF-Cys/Ser{sub 108/121} and HB-EGF-Cys/Ser{sub 116/132} stable cell lines which exhibited accumulated expression immediately outside the nucleus. rHB-EGF, HB-EGF, and HB-EGF{sub 134/143} proteins competed with {sup 125}I-EGF in an A431 competitive binding assay, whereas HB-EGF-Cys/Ser{sub 108/121} and HB-EGF-Cys/Ser{sub 116/132} failed to compete. Each HB-EGF disulfide analogue lacked the ability to stimulate tyrosine phosphorylation of the 170 kDa EGFR. These results suggest that HB-EGF-Cys/Ser{sub 134/143} antagonizes EGFRs.

  15. Radioisotope Characterization of HB Line Low Activity Waste

    SciTech Connect

    Snyder, S.J.

    1999-08-05

    The purpose of this document is to provide a physical, chemical, hazardous and radiological characterization of Low-Level Waste (LLW) generated in HB-Line as required by the 1S Manual, Savannah River Site Waste Acceptance Criteria Manual.

  16. Photocopy of drawing. VAB HB2 & 4 ET HOLDING CELLS, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Photocopy of drawing. VAB HB-2 & 4 ET HOLDING CELLS, UPGRADE TO CHECKOUT CELLS. NASA John F. Kennedy Space Center, Florida. File Number 79K33180, Reynolds, Smith & Hill, February 1991. H.B.-2, PLANS AT LEVELS 4,5,&6. Sheet 7 - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

  17. Photocopy of drawing. VAB HB2 & 4 ET HOLDING CELLS, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Photocopy of drawing. VAB HB-2 & 4 ET HOLDING CELLS, UPGRADE TO CHECKOUT CELLS. NASA John F. Kennedy Space Center, Florida. File Number 79K33180, Reynolds, Smith & Hill, February 1991. H.B.-2, PLANS AT LEVELS 7,8,&9. Sheet 8 - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

  18. Photocopy of drawing. VAB HB2 & 4 ET HOLDING CELLS, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Photocopy of drawing. VAB HB-2 & 4 ET HOLDING CELLS, UPGRADE TO CHECKOUT CELLS. NASA John F. Kennedy Space Center, Florida. File Number 79K33180, Reynolds, Smith & Hill, February 1991. H.B.-2, PLANS AT LEVELS 1,2,&3. Sheet 6 - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

  19. Transient neonatal cyanosis associated with a new Hb F variant: Hb F viseu.

    PubMed

    Bento, Celeste; Magalhães Maia, Tabita; Carvalhais, Ines; Moita, Filipa; Abreu, Gabriela; Relvas, Luis; Pereira, Alexandra; Farela Neves, José; Ribeiro, Maria L

    2013-03-01

    Neonatal cyanosis in healthy newborns can be associated either with methemoglobin due to cytochrome b5 reductase deficiency or to M-hemoglobin, a group of hemoglobin variants resulting from mutations in the globin chain genes. We report the clinical case of a neonate with cyanosis and normal cardiac and respiratory function. At birth the hematological parameters were normal; however, the methemoglobinemia was 16%. Spontaneously, the cyanosis gradually decreased and by the fifth month of age the methemoglobin level was normal. A heterozygous Gγ-globin gene (HBG2) missense mutation 87 C-A (Leu28Met) was identified. His father, with a history of transfusion in the neonatal period, is heterozygous for the same mutation. This hemoglobin variant, not previously described, was called Hb F Viseu and is the sixth Gγ-chain variant reported in association with neonatal cyanosis.

  20. Rubber particle proteins, HbREF and HbSRPP, show different interactions with model membranes.

    PubMed

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

    2014-01-01

    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.

  1. A field effect transistor (FET)-based immunosensor for detection of HbA1c and Hb.

    PubMed

    Bian, Chao; Tong, Jianhua; Sun, Jizhou; Zhang, Hong; Xue, Qiannan; Xia, Shanhong

    2011-04-01

    A field effect transistor (FET)-based immunosensor was developed for diabetes monitoring by detecting the concentrations of glycated hemoglobin (HbA1c) and hemoglobin (Hb). This immunosensor consists of a FET-based sensor chip and a disposable extended-gate electrode chip. The sensor chip was fabricated by standard CMOS process and was integrated with signal readout circuit. The disposable electrode chip, fabricated on polyester plastic board by Micro-Electro-Mechanical-Systems (MEMS) technique, was integrated with electrodes array and micro reaction pool. Biomolecules were immobilized on the electrode based on self-assembled monolayer and gold nanoparticles. Experimental results showed that the immunosensor achieved a linear response to HbA1c with the concentration from 4 to 24 μg/ml, and a linear response to Hb with the concentration from 60 to 180 μg/ml.

  2. HB-Line Plutonium Oxide Data Collection Strategy

    SciTech Connect

    Watkins, R.; Varble, J.; Jordan, J.

    2015-05-26

    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

  3. Haemoglobin J-Baltimore can be detected by HbA1c electropherogram but with underestimated HbA1c value.

    PubMed

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

    2016-01-01

    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.

  4. 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.

    PubMed

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

    2015-08-01

    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.

  5. Bioconversion of glycerine pitch into a novel yellow-pigmented P(3HB-co-4HB) copolymer: synergistic effect of ammonium acetate and polymer characteristics.

    PubMed

    Ramachandran, Hema; Amirul, A A

    2014-01-01

    Glycerine pitch waste generated from oleochemical industry was exploited as a carbon source for poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P(3HB-co-4HB)) copolymer production by a novel, yellow-pigmented bacterium Cupriavidus sp. USMAHM13 to improve the economics of microbial polyhydroxyalkanoate production and to establish a feasible waste management approach. Medium optimization using response surface methodology through shake-flask fermentation had led to the accumulation of P(3HB-co-51%4HB) copolymer using a combination of glycerine pitch (10 g/l), 1,4-butanediol (8.14 g/l), and ammonium acetate (2.39 g/l). P(3HB-co-4HB) copolymers with 4HB monomer compositions ranged from 3 to 40 mol% were obtained through batch fermentation in a bioreactor using different concentrations of ammonium acetate. The copolymers exhibited a wide range of material properties depending on the monomer composition and type of carbon sources. P(3HB-co-40%4HB) was a typical random copolymer, whereas other P(3HB-co-4HB) produced were blend copolymers. Carotenoid pigment which was produced simultaneously with the polymer production was found to have negligible effect on the mechanical and thermal properties of the P(3HB-co-4HB) copolymer films.

  6. The History of GalaFLEX P4HB Scaffold

    PubMed Central

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

    2016-01-01

    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 fully resorbable products provides prolonged strength retention, typically 50% to 70% strength retention at 12 weeks, and facilitates remodeling in vivo to provide a strong, lasting repair. P4HB belongs to a naturally occurring class of biopolymers and fibers made from it are uniquely strong, flexible, and biocompatible. GalaFLEX Scaffold is comprised of high-strength, resorbable P4HB monofilament fibers. It is a knitted macroporous scaffold intended to elevate, reinforce, and repair soft tissue. The scaffold acts as a lattice for new tissue growth, which is rapidly vascularized and becomes fully integrated with adjacent tissue as the fibers resorb. In this review, we describe the development of P4HB, its production, properties, safety, and biocompatibility of devices made from P4HB. Early clinical results and current clinical applications of products made from P4HB are also discussed. The results of post-market clinical studies evaluating the GalaFLEX Scaffold in rhytidectomy and cosmetic breast surgery demonstrate that the scaffold can reinforce lifted soft tissue, resulting in persistent surgical results in the face and neck at one year, and provide lower pole stability after breast lift at one year. PMID:27697885

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

    PubMed

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

    2016-03-15

    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.

  8. A simple method for HbF analysis.

    PubMed

    von Mandach, U; Tuchschmid, P; Huch, A; Huch, R

    1987-01-01

    Spectrophotometric methods with CO-oxymeters for measurements of carboxyhemoglobin and/or oxygen saturation in human blood include a systematic error depending on the percentage of fetal hemoglobin. It is of clinical importance to estimate the fetal hemoglobin to correct HbCO and SO2 values respectively. The described method is simple and less time consuming than conventional methods like HPLC or electrophoresis. The two measurements of oxy- and carboxyhemoglobin in the same blood sample with different oxygen saturation are needed for the estimation of the HbF and can be performed, including the deoxygenation procedure, in about 40 minutes.

  9. Impact of glutathione-HbA1c on HbA1c measurement in diabetes diagnosis via array isoelectric focusing, liquid chromatography, mass spectrometry and ELISA.

    PubMed

    Li, Si; Guo, Chen-Gang; Chen, Lu; Yin, Xiao-Yang; Wu, Yi-Xin; Fan, Liu-Yin; Fan, Hui-Zhi; Cao, Cheng-Xi

    2013-10-15

    Hemoglobin A1c (HbA1c) has been proven to be a key biomarker for diabetes screening, and glutathiolation of HbA1c (viz., GSS-HbA1c) has been identified. However, the impact of GSS-HbA1c on the measurement of HbA1c for diabetes screening has not been quantitatively assessed yet. To address the issue, the micropreparative capillary isoelectric focusing (cIEF) developed in our previous work was used for the high resolution separation and purification of hemoglobin (Hb) species. The main fractions of HbA0, HbA3 and HbA1c extracted from the developed cIEF were identified by validated Mono S method. The proposed GSS-HbA1c fractions in the cIEF were pooled and identified by electrospray ionization mass spectrometry (ESI-MS). The HbA1c enzyme-linked immunosorbent assay (ELISA) kit was employed for further quantitative analysis of GSS-HbA1c. A total of 34 blood samples with HbA1c levels from 4.2% to 13.4% were assessed via the above comprehensive strategy of IEF-HPLC-MS-ELISA. It was demonstrated that the HbA1c levels detected by cation exchange LC were considerably influenced by the glutathiolation of Hb and the range of detected GSS-HbA1c values was between 0.23% and 0.74%. The results and developed cIEF methods have considerable significances for investigation of diabetes and clinical diagnosis.

  10. Pregnancy outcome in patients with sickle cell disease in the UK--a national cohort study comparing sickle cell anaemia (HbSS) with HbSC disease.

    PubMed

    Oteng-Ntim, Eugene; Ayensah, Benjamin; Knight, Marian; Howard, Jo

    2015-04-01

    We describe the findings from a national study of maternal and fetal outcomes of pregnancy in women with sickle cell disease (SCD). Data were collected via the United Kingdom Obstetric Surveillance System between 1 February 2010 and 31 January 2011 from 109 women, of whom 51 (46·8%) had HbSS and 44 (40·4%) had HbSC. Data included antenatal, maternal and fetal outcomes. Comparisons were made between women with HbSS and HbSC. Incidence of complications were acute pain (57%), blood transfusion (26%), urinary tract infection (UTI; 12%) and critical care unit admission (23%) and these were all more common in women with HbSS than HbSC. There was no difference in the incidence of acute chest syndrome, hypertension and venous thromboembolism between HbSS and HbSC. Women with HbSS were more likely to deliver at <37 weeks gestation (P = 0·01) and their babies were more likely to have reduced birth weight. Delivery at <34 weeks was increased in both HbSS and HbSC women (5·9% vs. 4·6%) compared to national data. This study confirms a high rate of maternal and fetal complications in mothers with SCD, even in women with HbSC, which has previously been considered to have a more benign phenotype in pregnancy.

  11. Photocopy of drawing. VAB HB2 & 4 ET HOLDING CELLS, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Photocopy of drawing. VAB HB-2 & 4 ET HOLDING CELLS, UPGRADE TO CHECKOUT CELLS. NASA John F. Kennedy Space Center, Florida. File Number 79K33180, Reynolds, Smith & Hill, February 1991. GENERAL ARRANGEMENT, PLAN & ELEVATIONS. Sheet 4 - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

  12. Photocopy of drawing. VAB HB2 & 4 ET HOLDING CELLS, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Photocopy of drawing. VAB HB-2 & 4 ET HOLDING CELLS, UPGRADE TO CHECKOUT CELLS. NASA John F. Kennedy Space Center, Florida. File Number 79K33180, Reynolds, Smith & Hill, February 1991. HINGED PANEL EQUIPMENT SCHEDULE. Sheet 28 - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

  13. Hb Wilde and Hb Patagonia: two novel elongated beta-globin variants causing dominant beta-thalassemia.

    PubMed

    Scheps, Karen G; Hasenahuer, Marcia A; Parisi, Gustavo; Fornasari, María S; Pennesi, Sandra P; Erramouspe, Beatriz; Basack, Felisa N; Veber, Ernesto S; Aversa, Luis; Elena, Graciela; Varela, Viviana

    2015-06-01

    We describe here the molecular and hematological characteristics of novel frameshift mutations in exon 2 of the HBB gene (in heterozygous state) found in two Argentinean pediatric patients with dominant β-thalassemia-like features. In Hb Wilde, HBB:c.270_273delTGAG(p.Glu90Cysfs*67), we detected the deletion of the third base of the codon 89 (T) and the codon 90 (GAG), whereas in Hb Patagonia, HBB:c.296_297dupGT(p.Asp99Trpfs*59), the frameshift mutation was due to a duplication of a 'GT' dinucleotide after the second base of codon 98 (GTG). The Hb Patagonia and Hb Wilde mutations would result in elongated β-globin chains with modified C-terminal sequences and a total of 155 and 157 amino acids residues, respectively. Based on bioinformatics and structural analysis, as well as protein modeling, we predict that the elongated β-globins would affect the formation of the αβ dimers and their stability, which would further support the mechanism for the observed clinical features in both patients.

  14. Complex interaction of Hb Q-Thailand and Hb E with alpha(0)-thalassemia and hereditary persistence of fetal hemoglobin in a Chinese family.

    PubMed

    Zheng, Weidong; Liu, Yanhui; Chen, Dong; Rong, Kabin; Ge, Yanfen; Gong, Caiping; Chen, Heping

    2010-09-01

    Hemoglobin (Hb) Q-Thailand, Hb E, and other forms of thalassemia are prevalent in Southeast Asia including China. We report a hitherto undescribed condition in which four forms of Hb defects co-segregate. The proband was a 20-year-old Chinese man who presented with moderate hypochromic microcytosis with Hb 73 g/l, hematocrit (Hct) 27.0%, mean corpuscular volume 57.6 fl, mean corpuscular hemoglobin 15.5 pg, and mean corpuscular hemoglobin concentration (MCHC) 268.0 g/l. Both Hb electrophoresis and high-performance liquid chromatography analysis revealed abnormal Hbs. DNA analysis demonstrated that the proband was a double heterozygote of Hb Q-Thailand and Hb E in combination with alpha(0)-thalassemia and Southeast Asian-type hereditary persistence of fetal hemoglobin (SEA-HPFH). Family study identified that her father was a double heterozygote for Hb Q-Thailand and Hb E, whereas her mother was a heterozygote for SEA-HPFH with alpha(0)-thalassemia. Moreover, his brother was a classical Hb QH disease patient. The genotype-phenotype relationship observed in this Chinese family with complex thalassemia syndromes is presented. This work will provide some clinical implications for molecular diagnosis for complex hemoglobinopathies.

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

    PubMed Central

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

    2016-01-01

    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. PMID:27375647

  16. Hb E/beta-thalassaemia: a common & clinically diverse disorder.

    PubMed

    Olivieri, Nancy F; Pakbaz, Zahra; Vichinsky, Elliott

    2011-10-01

    Haemoglobin E-beta thalassaemia (Hb E/β-thalassaemia) is the genotype responsible for approximately one-half of all severe beta-thalassaemia worldwide. The disorder is characterized by marked clinical variability, ranging from a mild and asymptomatic anaemia to a life-threatening disorder requiring transfusions from infancy. The phenotypic variability of Hb E/β-thalassaemia and the paucity of long-term clinical data, present challenges in providing definitive recommendations for the optimal management of patients. Genetic factors influencing the severity of this disorder include the type of beta-thalassaemia mutation, the co-inheritance of alpha-thalassaemia, and polymorphisms associated with increased production of foetal haemoglobin. Other factors, including a variable increase in serum erythropoietin in response to anaemia, previous or ongoing infection with malaria, previous splenectomy and other environmental influences, may be involved. The remarkable variation, and the instability, of the clinical phenotype of Hb E beta-thalassaemia suggests that careful tailoring of treatment is required for each patient, and that therapeutic approaches should be re-assessed over-time.

  17. Developing a reference system for the IFCC standardization of HbA2.

    PubMed

    Paleari, Renata; Caruso, Donatella; Kaiser, Patricia; Arsene, Cristian Gabriel; Schaeffer-Reiss, Christine; Van Dorsselaer, Alain; Bissé, Emmanuel; Ospina, Maria; De Jesús, Víctor R; Wild, Barbara; Mosca, Andrea

    2016-05-27

    The importance of hemoglobin A2 (HbA2) as an indicator of the presence of β-thalassemia was established many years ago. However, clinical application of recommended HbA2 cut off values is often hampered due to poor equivalence of HbA2 results among methods and laboratories. Thus, the IFCC standardization program for HbA2 was initiated in 2004 with the goal of achieving a complete reference system for this measurand. HbA2 standardization efforts are still in progress, including the development of a higher-order HbA2 reference measurement procedure and the preparation of a certified reference material in collaboration with the IRMM. Here, we review the past, present and future of HbA2 standardization and describe the current status of HbA2 testing.

  18. A new hemoglobin variant found during Hb A1c measurement: Hb Hokusetsu [beta52(D3)Asp-->Gly].

    PubMed

    Nakanishi, T; Miyazaki, A; Kishikawa, M; Shimizu, A; Kishida, O; Sumi, S; Tsubakio, T; Imai, K

    1998-07-01

    A new beta chain variant was accidentally found through the assay of Hb A1c in a diabetic patient. The variant was detected by polyacrylamide gel isoelectrofocusing and electrospray ionization mass spectrometry. For sequence determination, globin was cleaved with combination of trypsin and lysyl endopeptidase and analyzed by high performance liquid chromatography connected to electrospray ionization mass spectrometry. An abnormal betaT-5 peptide was found by reconstructed selected ion monitoring. The collision-induced dissociation spectrum of an ion derived from the abnormal betaT-5 peptide revealed a new substitution, [beta52(D3)Asp-->Gly], named Hb Hokusetsu. The sequence was confirmed with an automatic sequencer using peptides isolated by reversed phase high performance liquid chromatography. Amplification of the beta-globin exon 2 and nucleotide sequencing revealed a GAT-->GGT mutation in codon 52 corresponding to an Asp-->Gly replacement. Electrospray ionization mass spectrometry analysis of the hemolysate showed a reasonable value of 10.4% for glycated globin. The variant migrated as Hb S on isoelectrofocusing. Hematological analysis revealed normal parameters. The patient's hemolysate showed normal stability in the isopropanol test. Oxygen equilibrium studies on the patient's red blood cells and hemolysate showed no significant change in oxygen affinity or cooperativity.

  19. The Long and Winding Road to Optimal HbA1c Measurement

    PubMed Central

    Little, Randie R.; Rohlfing, Curt

    2016-01-01

    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

  20. Hb Southern Italy: coexistence of two missence mutations (the Hb Sun Prairie alpha2 130 Ala --> Pro and Hb Caserta alpha2 26 Ala --> Thr) in a single HBA2 gene.

    PubMed

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

    2008-10-01

    This study describes a new molecular condition in the alpha(2)-globin gene (HBA2) found in six unrelated families from Southern Italy (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). Hb Sun Prairie was originally observed in Indian patients in either the homozygous state, with severe hemolytic anemia, and in the heterozygous state with microcytosis, or in asymptomatic cases as an alpha-thalassemia carrier phenotype. Hb Caserta was observed for the first time in a Casertian family (South Italy) that displayed a slowmigrating haemoglobin upon investigation. We report the clinical phenotype and molecular study of this new double mutant form of haemoglobin in heterozygous and homozygous subjects, as well as in association with alpha degrees delectional thalassemia.

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

    PubMed

    Vigneswari, S; Murugaiyah, V; Kaur, G; Abdul Khalil, H P S; Amirul, A A

    2016-09-01

    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 20mol% 4HB [53.2°], P(3HB-co-35mol%4HB)[48.9°], P(3HB-co-50mol%4HB)[44.5°] and P(3HB-co-82mol%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.

  2. Solids loading evaluation for HB-line scrap recovery filters

    SciTech Connect

    Crowder, M.L.

    2000-08-08

    The HB-Line Scrap Recovery facility uses wire screen filters to remove solids from plutonium-containing solutions transferred from the slab tank dissolvers. At times, the accumulation of solids is large enough to cause blinding (i.e., pluggage) of the filters. If the solids contain undissolved plutonium, significant accumulation of fissile material could impact operations. To address this potential issue, experiments were performed to define the minimum solids required to completely blind a filter. The solids loading experiments were performed by arranging 25- and 10-{micro}m HB-Line filters in series to simulate the equipment in the scrap recovery process. Separate tests were performed using coarse and fine glass frit and cerium oxide powder suspended in 35 wt% sodium nitrate solution using a small turbine mixer. The solution and solids were transferred from a reservoir through the filter housings by vacuum. In each case, the 25-{micro}m filter blinded first and was full of wet cake. After drying and accounting for the sodium nitrate in the filter cake, the following results were obtained. The results of the solids loading tests demonstrated that at least 800 g of solids accumulated in the filter housing before flow stopped. The actual amount of collected material was dependent upon the physical properties of the solids such as density and particle size. The mass of solids collected by the blinded 25-{micro}m filter increased when successively finer solids were used in the experiments. Based on these results, one should anticipate that filters in the HB-Line Scrap Recovery Facility have the potential to collect similar quantities of material before transfer of solution from the dissolvers is severely impacted.

  3. Electric dipole moments of Escherichia coli HB 101.

    PubMed

    Stoylov, Stoyl P; Gyurova, Anna Y; Bunin, Viktor; Angersbach, Alexander; Georgieva, Ralitsa N; Danova, Svetla T

    2009-04-01

    The theoretical and experimental studies of the particles' electric dipole moments in the microscopic and submicroscopic size range show that in the case of polar and conductive media the interfacial components of the dipole moments are of greatest importance. While in the range of manometer's sizes there seems to be no important problems in the identification and in the estimation of the values of the dipole moments at present, in the micrometer range there are serious problems. In this communication these problems are considered and illustrated by electro-optic investigations of Escherichia coli HB 101.

  4. Use of fructosyl peptide oxidase for HbA1c assay.

    PubMed

    Yonehara, Satoshi; Inamura, Norio; Fukuda, Miho; Sugiyama, Koji

    2015-03-01

    ARKRAY, Inc developed the world's first automatic glycohemoglobin analyzer based on HPLC (1981). After that, ARKRAY developed enzymatic HbA1c assay "CinQ HbA1c" with the spread and diversification of HbA1c measurement (2007). CinQ HbA1c is the kit of Clinical Chemistry Analyzer, which uses fructosyl peptide oxidase (FPOX) for a measurement reaction. This report mainly indicates the developmental background, measurement principle, and future of the enzymatic method HbA1c reagent.

  5. Molecular Cloning of HbPR-1 Gene from Rubber Tree, Expression of HbPR-1 Gene in Nicotiana benthamiana and Its Inhibition of Phytophthora palmivora

    PubMed Central

    Khunjan, Uraiwan; Ekchaweng, Kitiya; Panrat, Tanate; Tian, Miaoying; Churngchow, Nunta

    2016-01-01

    This is the first report to present a full-length cDNA (designated HbPR-1) encoding a putative basic HbPR-1 protein from rubber tree (Hevea brasiliensis) treated with salicylic acid. It was characterized and also expressed in Nicotiana benthamiana using Agrobacterium-mediated transient gene expression system in order to investigate the role of HbPR-1 gene in rubber tree against its oomycete pathogen Phytopthora palmivora and to produce recombinant HbPR-1 protein for microbial inhibition test. The HbPR-1 cDNA was 647 bp long and contained an open reading frame of 492 nucleotides encoding 163 amino acid residues with a predicted molecular mass of 17,681 Da and an isoelectric point (pI) of 8.56, demonstrating that HbPR-1 protein belongs to the basic PR-1 type. The predicted 3D structure of HbPR-1 was composed of four α-helices, three β-sheets, seven strands, and one junction loop. Expression and purification of recombinant HbPR-1 protein were successful using Agrobacterium-mediated transient expression and one-step of affinity chromatography. Heterologous expression of HbPR-1 in N. benthamiana reduced necrosis areas which were inoculated with P. palmivora zoospores, indicating that the expressed HbPR-1 protein played an important role in plant resistance to pathogens. The purified recombinant HbPR-1 protein was found to inhibit 64% of P. palmivora zoospore germination on a water agar plate compared with control, suggesting that it was an antimicrobial protein against P. palmivora. PMID:27337148

  6. Molecular Cloning of HbPR-1 Gene from Rubber Tree, Expression of HbPR-1 Gene in Nicotiana benthamiana and Its Inhibition of Phytophthora palmivora.

    PubMed

    Khunjan, Uraiwan; Ekchaweng, Kitiya; Panrat, Tanate; Tian, Miaoying; Churngchow, Nunta

    2016-01-01

    This is the first report to present a full-length cDNA (designated HbPR-1) encoding a putative basic HbPR-1 protein from rubber tree (Hevea brasiliensis) treated with salicylic acid. It was characterized and also expressed in Nicotiana benthamiana using Agrobacterium-mediated transient gene expression system in order to investigate the role of HbPR-1 gene in rubber tree against its oomycete pathogen Phytopthora palmivora and to produce recombinant HbPR-1 protein for microbial inhibition test. The HbPR-1 cDNA was 647 bp long and contained an open reading frame of 492 nucleotides encoding 163 amino acid residues with a predicted molecular mass of 17,681 Da and an isoelectric point (pI) of 8.56, demonstrating that HbPR-1 protein belongs to the basic PR-1 type. The predicted 3D structure of HbPR-1 was composed of four α-helices, three β-sheets, seven strands, and one junction loop. Expression and purification of recombinant HbPR-1 protein were successful using Agrobacterium-mediated transient expression and one-step of affinity chromatography. Heterologous expression of HbPR-1 in N. benthamiana reduced necrosis areas which were inoculated with P. palmivora zoospores, indicating that the expressed HbPR-1 protein played an important role in plant resistance to pathogens. The purified recombinant HbPR-1 protein was found to inhibit 64% of P. palmivora zoospore germination on a water agar plate compared with control, suggesting that it was an antimicrobial protein against P. palmivora.

  7. Membrane-associated HB-EGF modulates HGF-induced cellular responses in MDCK cells.

    PubMed

    Singh, Amar B; Tsukada, Toshiaki; Zent, Roy; Harris, Raymond C

    2004-03-15

    In MDCK cells, hepatocyte growth factor/scatter factor (HGF/SF) induces epithelial cell dissociation, scattering, migration, growth and formation of branched tubular structures. By contrast, these cells neither scatter nor form tubular structures in response to the epidermal growth factor (EGF) family of growth factors. Heparin-binding EGF-like growth factor (HB-EGF) is a member of the EGF family of growth factors and is synthesized as a membrane-associated precursor molecule (proHB-EGF). ProHB-EGF is proteolytically cleaved to release a soluble ligand (sHB-EGF) that activates the EGF receptor. Although recent studies suggest possible physiological functions, the role of proHB-EGF remains largely undefined. Using MDCK cells stably expressing proHB-EGF, a noncleavable deletion mutant of proHB-EGF or soluble HB-EGF, we show that epithelial cell functions differ depending on the form of HB-EGF being expressed. Expression of noncleavable membrane-anchored HB-EGF promoted cell-matrix and cell-cell interactions and decreased cell migration, HGF/SF-induced cell scattering and formation of tubular structures. By contrast, expression of soluble HB-EGF induced increased cell migration, decreased cell-matrix and cell-cell interactions and promoted the development of long unbranched tubular structures in response to HGF/SF. These findings suggest that HB-EGF can not only modulate HGF/SF-induced cellular responses in MDCK cells but also that membrane-bound HB-EGF and soluble HB-EGF give rise to distinctly different effects on cell-cell and cell-extracellular matrix interactions.

  8. Genetic analysis of lipolytic activities in Thermus thermophilus HB27.

    PubMed

    Leis, Benedikt; Angelov, Angel; Li, Haijuan; Liebl, Wolfgang

    2014-12-10

    The extremely thermophilic bacterium Thermus thermophilus HB27 displays lipolytic activity for the hydrolysis of triglycerides. In this study we performed a mutational in vivo analysis of esterases and lipases that confer growth on tributyrin. We interrupted 10 ORFs suspected to encode lipolytic enzymes. Two chromosomal loci were identified that resulted in reduced hydrolysis capabilities against tributyrin and various para-nitrophenyl acyl esters. By implementation of a convenient new one-step method which abstains from the use of selectable markers, a mutant strain with multiple scar-less deletions was constructed by sequentially deleting ORFs TT_C1787, TT_C0340, TT_C0341 and TT_C0904. The quadruple deletion mutant of T. thermophilus exhibited significantly lower lipolytic activity (approximately 25% residual activity compared to wild type strain) over a broad range of fatty acyl esters and had lost the ability to grow on agar plates containing tributyrin as the sole carbon source. Furthermore, we were able to determine the impact of each gene disruption on the lipolytic activity profile in this model organism and show that the esterase activity in T. thermophilus HB27 is due to a concerted action of several hydrolases having different substrate preferences and activities. The esterase-less T. thermophilus multi-deletion mutant from this study can be used as a screening and expression host for esterase genes from thermophiles or metagenomes.

  9. Two new beta-chain variants: Hb Tripoli [beta26(B8)Glu-->Ala] and Hb Tizi-Ouzou [beta29(B11)Gly-->Ser].

    PubMed

    Lacan, Philippe; Becchi, Michel; Zanella-Cleon, Isabelle; Aubry, Martine; Ffrench, Martine; Couprie, Nicole; Francina, Alain

    2004-08-01

    Two new beta-globin chain variants: Hb Tripoli: codon 26, GAG-->GCG [beta26(B8)Glu-->Ala] and Hb Tizi-Ouzou: codon 29, GGC-->AGC [beta29(B11)Gly-->Ser] are described on the first exon of the beta-globin gene. The two variants are characterized by DNA sequencing and mass spectrometry (MS). Hematological abnormalities were found in the two carriers. The presence of microcytosis and hypochromia is explained by an additional homozygous 3.7 kb alpha(+) thalassemic deletion for the carrier of Hb Tizi-Ouzou. Hb Tizi-Ouzou showed a slight instability in vitro. The same hematological abnormalities associated with anemia are difficult to explain for Hb Tripoli's carrier in the absence of an alpha-globin genes abnormality and could suggest a possible abnormal splicing.

  10. Performance of the Roche second generation hemoglobin A1c immunoassay in the presence of HB-S or HB-C traits.

    PubMed

    Abadie, Jude M; Koelsch, Angela A

    2008-01-01

    Blood HbA1c determination is a powerful tool for the evaluation and management of patients with diabetes mellitus. Many HbA1c analytical methods demonstrate bias in samples from patients with hemoglobinopathies. This study evaluated the analytical performance of Roche Diagnostics' 1st and 2nd generation HbA1c assays in patients with or without hemoglobinopathies whose HbA1c levels were elevated or normal, respectively. Boronate-affinity high performance liquid chromatography (HPLC) served as the reference method. Whole blood samples were collected from 80 patients with HbS or HbC whose group mean HbA1c value was elevated and also from 80 patients without hemoglobinopathy whose HbA1c values were in the well-controlled range. Each sample was assayed for HbA1c by the Primus boronate-affinity HPLC technique and by Roche's 1st and 2nd generation immunoassays using a Cobas Integra 800 analytical system. Results by the HPLC technique were compared with the results of both Roche assays by linear regression and Bland-Altman analysis. The 1st and 2nd generation assays yielded regression lines and correlation values vs HPLC assay of y = 1.43x - 1.59; R(2) = 0.83, and y = 0.94x + 0.10; R(2) = 0.92, respectively, in the 80 patients with hemoglobinopathies. The mean difference and the +/-2SD range were greater in the 1st than in the 2nd generation assay (2.68, +/-2.07 vs -0.54, +/-0.86, respectively). The 2nd generation assay also showed better performance than the 1st generation assay in samples from the 80 patients without hemoglobinopathy. In conclusion, this study validates the accuracy of Roche's 2nd generation assay, which is substantially improved over Roche's 1st generation HbA1c assay.

  11. Application of CRISPRi for prokaryotic metabolic engineering involving multiple genes, a case study: Controllable P(3HB-co-4HB) biosynthesis.

    PubMed

    Lv, Li; Ren, Yi-Lin; Chen, Jin-Chun; Wu, Qiong; Chen, Guo-Qiang

    2015-05-01

    Clustered regularly interspaced short palindromic repeats interference (CRISPRi) is used to edit eukaryotic genomes. Here, we show that CRISPRi can also be used for fine-tuning prokaryotic gene expression while simultaneously regulating multiple essential gene expression with less labor and time consumption. As a case study, CRISPRi was used to control polyhydroxyalkanoate (PHA) biosynthesis pathway flux and to adjust PHA composition. A pathway was constructed in Escherichia coli for the production of poly(3-hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-4HB)] from glucose. The native gene sad encoding E. coli succinate semi-aldehyde dehydrogenase was expressed under the control of CRISPRi using five specially designed single guide RNAs (sgRNAs) for regulating carbon flux to 4-hydroxybutyrate (4HB) biosynthesis. The system allowed formation of P(3HB-co-4HB) consisting of 1-9mol% 4HB. Additionally, succinate, generated by succinyl-coA synthetase and succinate dehydrogenase (respectively encoded by genes sucC, sucD and sdhA, sdhB) was channeled preferentially to the 4HB precursor by using selected sgRNAs such as sucC2, sucD2, sdhB2 and sdhA1 via CRISPRi. The resulting 4HB content in P(3HB-co-4HB) was found to range from 1.4 to 18.4mol% depending on the expression levels of down-regulated genes. The results show that CRISPRi is a feasible method to simultaneously manipulate multiple genes in E. coli.

  12. NITRATE CONVERSION OF HB-LINE REILLEXTM HPQ RESIN

    SciTech Connect

    Steimke, J.; Williams, M.; Steeper, T.; Leishear, R.

    2012-05-29

    Reillex{trademark} HPQ ion exchange resin is used by HB Line to remove plutonium from aqueous streams. Reillex{trademark} HPQ resin currently available from Vertellus Specialties LLC is a chloride ionic form, which can cause stress corrosion cracking in stainless steels. Therefore, HB Line Engineering requested that Savannah River National Laboratory (SRNL) convert resin from chloride form to nitrate form in the Engineering Development Laboratory (EDL). To perform this task, SRNL treated two batches of resin in 2012. The first batch of resin from Reilly Industries Batch 80302MA was initially treated at SRNL in 2001 to remove chloride. This batch of resin, nominally 30 liters, has been stored wet in carboys since that time until being retreated in 2012. The second batch of resin from Batch 23408 consisted of 50 kg of new resin purchased from Vertellus Specialties in 2012. Both batches were treated in a column designed to convert resin using downflow of 1.0 M sodium nitrate solution through the resin bed followed by rinsing with deionized water. Both batches were analyzed for chloride concentration, before and after treatment, using Neutron Activation Analysis (NAA). The resin specification [Werling, 2003] states the total chlorine and chloride concentration shall be less than 250 ppm. The resin condition for measuring this concentration is not specified; however, in service the resin would always be fully wet. Measurements in SRNL showed that changing from oven dry resin to fully wet resin, with liquid in the particle interstices but no supernatant, increases the total weight by a factor of at least three. Therefore, concentration of chlorine or chloride expressed as parts per million (ppm) decreases by a factor of three. Therefore, SRNL recommends measuring chlorine concentration on an oven dry basis, then dividing by three to estimate chloride concentration in the fully wet condition. Chloride concentration in the first batch (No.80302MA) was nearly the same

  13. Hb E-β-Thalassemia in Five Indian States.

    PubMed

    Italia, Khushnooma; Dabke, Pooja; Sawant, Pratibha; Nadkarni, Anita; Ghosh, Kanjaksha; Colah, Roshan B

    2016-09-01

    Hb E [β26(B8)Glu→Lys; HBB: c.79G > A]-β-thalassemia (β-thal) has an extremely variable clinical presentation. We report the clinical features of these patients from five Indian states together with their hematological and molecular characteristics. Seventy-eight Hb E-β-thal patients from different regions [West Bengal (30), Maharashtra (21), Uttar Pradesh (13), Bihar (11), Orissa (3)] were clinically evaluated along with hematological profiles and molecular characteristics (β-thal mutations, XmnI polymorphisms, α genotypes). Twenty-nine of the 78 patients had a mild clinical presentation (clinical score 2.2 ± 1.1), while 15 had moderate severity (clinical score 6.1 ± 1.2) with occasional transfusion needs, and 34 patients were severely affected (clinical score 8.2 ± 0.5) requiring regular blood transfusions. The age at clinical presentation in the severely affected patients was lower (6 months-10 years) as compared to those with milder symptoms (2 years-34 years). Thirty-four patients showed splenomegaly (spleen ≥3 cm below the costal margin) and five patients were splenectomized. The severe β(+ )IVS1-5 (G > C) (HBB: c.92 + 5G > C) was the most common β-thal mutation, while seven other mutations were also seen. The XmnI [+/+] and [-/-] polymorphisms were seen in 24.1 and 10.3% of mildly affected patients and 14.7 and 17.6% of severely affected patients respectively. A single α gene deletion (-α(3.7)/αα) was found in 20.7% of mildly affected and 5.9% of severely affected patients, respectively. No specific differences in the clinical, hematological or molecular characteristics were observed in the Hb E-β-thal patients from various geographic regions or different ethnic groups.

  14. Detection of HbA(1c) by boronate affinity immunoassay using bacterial magnetic particles.

    PubMed

    Tanaka, T; Matsunaga, T

    2001-12-01

    We have developed a boronate affinity immunoassay system using m-aminophenylboronic acid (mAPB) coupling to bacterial magnetic particles (BMPs). Homobifunctional crosslinker, Bis-(succcimidyl)suberate (BS3), was employed for preparation of mAPB-BMPs conjugates (mAPB-BMPs). Quantities of HbA(1c) on mAPB-BMPs were evaluated based on luminescence from alkaline phosphatase-conjugated anti-Hb antibody (ALP-antibody) binding to HbA(1c) on the BMP surface. The binding of HbA(1c) to mAPB-BMPs occurred gradually and was almost completed within 10 mm. The coupling reaction is enhanced due to static electric interaction between the positive charges on HbA(1c) and negative charges on BMPs. The amount of HbA(1c) binding to mAPB-BMPs increased with increasing sodium chloride concentrations in the range of 0-100 mM. However, the amount of Hb binding to mAPB-BMPs also increased in high concentration of sodium chloride. The Hb binding to mAPB-BMPs was detached from mAPB-BMPs when Hb-mAPB-BMPs were washed with low salt buffer. This indicates that Hb is nonspecifically adsorbed onto the surface of mAPB-BMPs in high concentration of sodium chloride. These results suggest that selective separation of HbA(1c) using mAPB-BMPs can be achieved with these conditions. A dose-response curve was obtained between luminescence intensity and HbA(1c) concentration using a fully automated boronate affinity immunoassay. A linear relationship between luminescence intensity and HbA(1c) concentration was obtained in the range of 10-10(4) ng/ml.

  15. Glycated Hemoglobin (HbA1c): Clinical Applications of a Mathematical Concept

    PubMed Central

    Leow, Melvin Khee Shing

    2016-01-01

    Background and purpose: Glycated hemoglobin (HbA1c) reflects the cumulative glucose exposure of erythrocytes over a preceding time frame proportional to erythrocyte survival. HbA1c is thus an areal function of the glucose-time curve, an educationally useful concept to aid teaching and clinical judgment. Methods: An ordinary differential equation is formulated as a parsimonious model of HbA1c. The integrated form yields HbA1c as an area-under-the-curve (AUC) of a glucose-time profile. The rate constant of the HbA1c model is then derived using the validated regression equation in the ADAG study that links mean blood glucose and HbA1c with a very high degree of goodness-of-fit. Results: This model has didactic utility to enable patients, biomedical students and clinicians to appreciate how HbA1c may be conceptually inferred from discrete blood glucose values using continuous glucose monitoring system (CGMS) or self-monitored blood glucose (SMBG) glucometer readings as shown in the examples. It can be appreciated how hypoglycemia can occur with rapid HbA1c decline despite poor glycemic control. Conclusions: Being independent of laboratory assay pitfalls, computed ‘virtual’ HbA1c serves as an invaluable internal consistency cross-check against laboratory-measured HbA1c discordant with SMBG readings suggestive of inaccurate/fraudulent glucometer records or hematologic disorders including thalassemia and hemoglobinopathy. This model could be implemented within portable glucometers, CGMS devices and even smartphone apps for deriving tentative ‘virtual’ HbA1c from serial glucose readings as an adjunct to measured HbA1c. Such predicted ‘virtual’ HbA1c readily accessible via glucometers may serve as feedback to modify behavior and empower diabetic patients to achieve better glycemic control. PMID:27708483

  16. NIR Flare of the quasar HB890736+017

    NASA Astrophysics Data System (ADS)

    Carrasco, L.; Recillas, E.; Porras, A.; Carraminana, A.

    2013-06-01

    We report that on May 19th, 2013, MJD 2456431.6350 the quasar HB89 0736+017 (z=0.1894) was found on a rising flux event, with a flux corresponding to H = 13.65 +/- 0.05. On this date, we found that the source had brightening by 0.45 mag in the H band with respect to the flux previously measured on MJD 2456343.83. The source is cross identified with the Gamma-Ray source 2FGL0739.2+0138, Observations were carried out with the 2.1m telescope of the Guillermo Haro Observatory operated by the National Institute for Astrophysics, Optics and Electronics (Mexico), equipped with the instrument CANICA a NIR camera.

  17. NIR brightening of the Quasar [HB89] 0133+476

    NASA Astrophysics Data System (ADS)

    Carrasco, L.; Luna, A.; Escobedo, G.; Mayya, D. Y.; Carraminana, A.

    2012-11-01

    We have observed a recent NIR brightening of the high redshift quasar HB890133+476 (z=0.856), a gamma ray source 1FGL J0137.0+4751. On October 23th,2012, epoch JD2456223.903056, we determined its flux in the H band to be 13.921 +/- 0.05. That is 0.9 magnitudes brighter than flux we had determined a month ago on epoch JD2456196.970671 H = 14.807 +/- 0.06. Observations were carried out with the 2.1m telescope of the Guillermo Haro Observatory operated by the National Institute for Astrophysics, Optics and Electronics (Mexico), equipped with the instrument CANICA a NIR camera.

  18. Two new G gamma chain variants: Hb F-Saint-Etienne [G gamma 79(EF3)Asp-->His] and Hb F-Lyon [G gamma 97(FG4)His-->Arg].

    PubMed

    Joly, Philippe; Lacan, Philippe; Garcia, Caroline; Berger, Claire; Perier, Christian; Barro, Claire; Francina, Alain

    2008-01-01

    Two new fetal hemoglobin (Hb F) variants affecting the (G)gamma chain are reported: Hb F-Saint-Etienne [G gamma 79(EF3)Asp-->His] and Hb F-Lyon [G gamma 97(FG4)His-->Arg]. These new Hb variants were found during a neonatal screening for hemoglobinopathies but characterized a few months later by our reference laboratory. The corresponding mutations are located on the external part of the Hb molecule and seem to be clinically silent.

  19. Hb Beograd [beta121(GH4)Glu-->Val, GAA-->GTA] in the Turkish population.

    PubMed

    Atalay, Ayfer; Koyuncu, Hasan; Köseler, Aylin; Ozkan, Anzel; Atalay, Erol O

    2007-01-01

    Hb Beograd [beta121(GH4)Glu-->Val, GAA-->GTA] is a rare variant first reported in Yugoslavia and then in Turkey, Australia and New Zealand. We report two further unrelated cases from Turkey. The importance of identifying Hb Beograd at the molecular level, especially in regions where Hb D-Los Angeles [beta121(GH4)Glu-->Gln, GAA-->CAA] is prevalent, is emphasized.

  20. Description of two new alpha variants: Hb Canuts [alpha85(F6)Asp-->His (alpha1)] and Hb Ambroise Pare [alpha117(GH5)Phe-->Ile (alpha2)]; two new beta variants: Hb Beaujolais [beta84(EF8)Thr-->Asn] and Hb Monplaisir [beta147 (Tyr-Lys-Leu-Ala-Phe-Phe-Leu-Leu-Ser-Asn-Phe-Tyr-158-COOH)] and one new delta variant: Hb (A2)North Africa [delta59(E3)Lys-->Met].

    PubMed

    Joly, Philippe; Lacan, Philippe; Bererd, Martine; Garcia, Caroline; Zanella-Cleon, Isabelle; Becchi, Michel; Aubry, Martine; Couprie, Nicole; Francina, Alain

    2009-01-01

    We present here five new hemoglobin (Hb) variants which have been identified during routine Hb analysis before their genotypic characterization. Four of these result from a classical missense mutation: Hb Canuts [alpha85(F6)Asp-->His (alpha1)], Hb Ambroise Pare [alpha117(GH5)Phe-->Ile (alpha2)], Hb Beaujolais [beta84(EF8)Thr-->Asn] and HbA(2)-North Africa [delta59(E3)Lys-->Met]. The last one, Hb Monplaisir [beta147 (Tyr-Lys-Leu-Ala-Phe-Phe-Leu-Leu-Ser-Asn-Phe-Tyr-158-COOH)], results from a frameshift mutation at the stop codon of the beta-globin gene which leads to a modified C-terminal sequence in the beta-globin chain. None of these variants seem to have a particular clinical expression in the heterozygous state. The circumstances of the discovery of these five new Hb variants emphasize the fact that an association of techniques is necessary for a complete screening of Hb variants during routine Hb analysis. Globin chain separation by reversed phase liquid chromatography (RP-LC) appears to be the most relevant method.

  1. Is There a Role for HbA1c in Pregnancy?

    PubMed

    Hughes, Ruth C E; Rowan, Janet; Florkowski, Chris M

    2016-01-01

    Outside pregnancy, HbA1c analysis is used for monitoring, screening for and diagnosing diabetes and prediabetes. During pregnancy, the role for HbA1c analysis is not yet established. Physiological changes lower HbA1c levels, and pregnancy-specific reference ranges may need to be recognised. Other factors that influence HbA1c are also important to consider, particularly since emerging data suggest that, in early pregnancy, HbA1c elevations close to the reference range may both identify women with underlying hyperglycaemia and be associated with adverse pregnancy outcomes. In later pregnancy, HbA1c analysis is less useful than an oral glucose tolerance test (OGTT) at detecting gestational diabetes. Postpartum, HbA1c analysis detects fewer women with abnormal glucose tolerance than an OGTT, but the ease of testing may improve follow-up rates and combining HbA1c analysis with fasting plasma glucose or waist circumference may improve detection rates. This article discusses the relevance of HbA1c testing at different stages of pregnancy.

  2. Two new hemoglobin variants: Hb Brem-sur-Mer [beta9(A6)Ser-->Tyr] and Hb Passy [alpha81(F2)Ser-->Pro (alpha2)].

    PubMed

    Lacan, Philippe; Moreau, Mathieu; Becchi, Michel; Zanella-Cleon, Isabelle; Aubry, Martine; Louis, Jean-Jacques; Couprie, Nicole; Francina, Alain

    2005-01-01

    Two new hemoglobin (Hb) variants: Hb Brem-sur-Mer [codon 9 (TCT-->TAT); beta9(A6)Ser-->Tyr] on the first exon of the beta-globin gene and Hb Passy [codon 81 (TCC-->CCC); alpha81(F2)Ser-->Pro (alpha2)] on the second exon of the alpha2-globin gene, are described. The two variants were characterized by DNA sequencing and mass spectrometry (MS). Hematological abnormalities: microcytosis and hypochromia were found only in the carrier of Hb Passy. In the absence of an association with an alpha-thalassemic deletion or mutation, the mutation 81(F2)Pro could induce a possible alpha-thalassemia (thal).

  3. [The effect of hyperbilirubinemia on the measurement of oxygenated hemoglobin (O2Hb), carboxyhemoglobin (COHb) and methemoglobin (MetHb) using multiwavelength oximeters in mixed venous blood].

    PubMed

    Lampert, R; Brandt, L

    1993-10-01

    Oximetric measurements are influenced by several mechanisms. Severe jaundice is one of these mechanisms with some clinical interest. In the literature it is pointed out that a high bilirubin concentration may falsify oximetric measurements and is often accompanied by elevated COHb levels. The reason for this phenomenon is thought to be an interference in the absorption spectra of haemoglobin derivatives and bilirubin [2, 3, 4, 10]. In our investigation we attempted to answer the following questions: 1. How do multiwavelength oximeters measure haemoglobin derivatives in different bilirubin concentrations? 2. Do different multiwavelength oximeters give different concentrations of haemoglobin derivatives? METHODS. In 13 patients who developed postoperative jaundice on the intensive care unit, O2Hb, COHb and MetHb were measured in mixed venous blood with two multiwavelength oximeters (OSM3, Radiometer; CO 2500, Ciba-Corning). Bilirubin concentration was measured by the DPD (dichlorphenyldiazonium) method in the central laboratory of our hospital. RESULTS. With increasing bilirubin concentrations, both oximeters measured increasing O2Hb values; the OSM3 consistently showed higher O2Hb concentrations than the CO 2500, with a maximal difference of 2.8% (Fig. 3). Regarding COHb, we saw clear increases in the values with increasing bilirubin concentrations (Fig. 4). The CO 2500 showed higher COHb values than the OSM3 (average 1.54 +/- 0.3%). The findings regarding MetHb differed. The CO 2500 showed increasing MetHb values as the bilirubin concentration increased (Fig. 5). All measurements exceeded normal values above a bilirubin concentration of 17 mg/dl. The OSM3, however, measured constant MetHb values which did not depend on jaundice. CONCLUSIONS. 1. The in vitro measurement of haemoglobin derivates by multiwavelength oximeters is influenced by hyperbilirubinaemia. This is caused by an interference between the light absorption spectra of the haemoglobin derivates and of

  4. Simulation Analysis for HB-Line Dissolver Mixing

    SciTech Connect

    Lee, S

    2006-03-22

    In support of the HB-Line Engineering agitator mixing project, flow pattern calculations have been made for a 90{sup o} apart and helical pitch agitator submerged in a flat tank containing dissolver baskets. The work is intended to determine maximum agitator speed to keep the dissolver baskets from contacting the agitator for the nominal tank liquid level. The analysis model was based on one dissolver basket located on the bottom surface of the flat tank for a conservative estimate. The modeling results will help determine acceptable agitator speeds and tank liquid levels to ensure that the dissolver basket is kept from contacting the agitator blade during HB-Line dissolver tank operations. The numerical modeling and calculations have been performed using a computational fluid dynamics approach. Three-dimensional steady-state momentum and continuity equations were used as the basic equations to estimate fluid motion driven by an agitator with four 90{sup o} pitched blades or three flat blades. Hydraulic conditions were fully turbulent (Reynolds number about 1 x 10{sup 5}). A standard two-equation turbulence model ({kappa},{var_epsilon}), was used to capture turbulent eddy motion. The commercial finite volume code, Fluent [5], was used to create a prototypic geometry file with a non-orthogonal mesh. Hybrid meshing was used to fill the computational region between the round-edged tank bottom and agitator regions. The nominal calculations and a series of sensitivity runs were made to investigate the impact of flow patterns on the lifting behavior of the dissolver basket. At high rotational speeds and low tank levels, local turbulent flow reaches the critical condition for the dissolver basket to be picked up from the tank floor and to touch the agitator blades during the tank mixing operations. This is not desirable in terms of mixing performance. The modeling results demonstrate that the flow patterns driven by the agitators considered here are not strong enough to

  5. Mechanisms and kinetics of melting of HbS aggregates studied in high concentration phosphate buffer

    NASA Astrophysics Data System (ADS)

    Aroutiounian, Svetlana

    The importance of melting kinetics in the pathogenesis of sickle cell disease originates from the inhibition of sickle hemoglobin polymer formation by the presence of oxygen. Sickle hemoglobin polymers form in the absence of oxygen or similar ligands, like carbon monoxide (CO). Melting of HbS polymers is initiated when red cells enter the lungs. Under the double nucleation mechanism, the formation of a sickle hemoglobin (HbS) polymer is composed of two events. Homogeneous nucleation with a characteristic delay time is prior to heterogeneous nucleation, which shows an avalanche-like kinetics. Two thirds of the transit time through the circulatory system, red cells spend under hypoxic conditions. In this work the role that ligand saturation plays in the kinetics of HbS polymer melting is investigated. There are two possible pathways connecting the initial and final states, direct ligation of molecules bound to the polymers followed by melting of ligated molecule, and melting of deoxy molecules followed by ligation of free molecules. Hence four kinetic rates describe the relaxation: two rates for CO binding (one to monomer phase Hb and one to polymer phase Hb) and two for Hb dissociation from polymers (one for CO-ligated Hb and for deoxyHb). We examine two models that gradually incorporate CO presence into the mechanism of polymer melting. The Homogeneous Model (HM) describes the melting of HbS polymers due to dilution and CO binding of HbS. We assume that the melting starts with the dissociation of monomers from the fiber ends. As a result the polymer concentration remains unchanged at the beginning of melting. The Simple Ends Model (SEM) describes melting from HbS fiber ends when melting is induced by diluting with deoxy buffer (DMM). The extended Ends Model (EEM) describes melting of HbS aggregates with dissociation of monomers from fiber ends when CO fully saturated buffer is applied. An additional (second) assumption is that the CO molecules bind only to free Hb

  6. HbS Binding to GP1bα Activates Platelets in Sickle Cell Disease

    PubMed Central

    Gupta, Avinash; Chawla, Sheetal; Batra, Harish; Seth, Tulika

    2016-01-01

    Intravascular hemolysis increases the risk of thrombosis in hemolytic disorders. Our previous study showed that the binding of adult hemoglobin (HbA) to glycoprotein (GP) 1bα induced the activation of platelets. The elevated plasma Hb or platelet surface bound Hb positively correlated with platelet activation in patients with paroxysmal nocturnal hemoglobinuria (PNH). Furthermore, this study shows that the sickle Hb [HbS, occurs due to single nucleotide polymorphism at A>T of β-globin gene of Hb and causes sickle cell disease (SCD)] also bound to GP1bα and activated platelets in a concentration-dependent manner. The HbS bound to glycocalicin (extramembranous part of GP1bα) with KD ~ 10.46 ± 3 μM. HbS induced phosphorylation of signaling adapter proteins, such as Lyn, PI3K, Akt and ERK in platelets, and also increased the surface expression of platelet activation markers such as P-selectin (10.7 fold) and PAC1 binding (10.4 fold) in platelet surface in a concentration-dependent manner. HbS also increased the platelet microparticle-generation (4.7 fold) and thrombus-formation (4.3 fold) in a concentration-dependent manner. An elevated level of extracellular Hb in plasma correlated directly with platelet activation markers such as P-selectin (r = 0.7947), PAC1 binding (r = 0.5914) on platelet surface and plasma levels of platelet-derived microparticles (r = 0.7834) in patients with SCD. Our study therefore suggests that the HbS-induced platelet activation may play a crucial role in intravascular clot formation observed in SCD patients characterized by high propensity to vascular occlusion and hypercoagulable states. PMID:27936141

  7. Osteocyte-derived HB-GAM (pleiotrophin) is associated with bone formation and mechanical loading.

    PubMed

    Imai, S; Heino, T J; Hienola, A; Kurata, K; Büki, K; Matsusue, Y; Väänänen, H K; Rauvala, H

    2009-05-01

    HB-GAM (also known as pleiotrophin) is a cell matrix-associated protein that is highly expressed in bone. It affects osteoblast function, and might therefore play a role in bone development and remodeling. We aimed to investigate the role of HB-GAM in bone in vivo and in vitro. The bones of HB-GAM deficient mice with an inbred mouse background were studied by histological, histomorphometrical, radiological, biomechanical and mu-CT analyses and the effect of immobilization was evaluated. HB-GAM localization in vivo was studied. MLO-Y4 osteocytes were subjected to fluid shear stress in vitro, and gene and protein expression were studied by subtractive hybridization, quantitative PCR and Western blot. Human osteoclasts were cultured in the presence of rhHB-GAM and their formation and resorption activities were assayed. In agreement with previous reports, the skeletal structure of the HB-GAM knockout mice developed normally. However, a growth retardation of the weight-bearing bones was observed by 2 months of age, suggesting a link to physical activity. Adult HB-GAM deficient mice were characterized by low bone formation and osteopenia, as well as resistance to immobilization-dependent bone remodeling. HB-GAM was localized around osteocytes and their processes in vivo and furthermore, osteocytic HB-GAM expression was upregulated by mechanical loading in vitro. HB-GAM did not affect on human osteoclast formation or resorption in vitro. Taken together, our results suggest that HB-GAM is an osteocyte-derived factor that could participate in mediating the osteogenic effects of mechanical loading on bone.

  8. Expression of HB-EGF by retinal pigment epithelial cells in vitreoretinal proliferative disease.

    PubMed

    Hollborn, Margrit; Iandiev, Ianors; Seifert, Marlen; Schnurrbusch, Ute E K; Wolf, Sebastian; Wiedemann, Peter; Bringmann, Andreas; Kohen, Leon

    2006-10-01

    The heparin-binding epidermal growth factor-like growth factor (HB-EGF) has been implicated in wound-healing processes of various tissues. However, it is not known whether HB-EGF may represent a factor implicated in overstimulated wound-healing processes of the retina during proliferative retinopathies. Therefore, we investigated whether human retinal pigment epithelial (RPE) cells, which are crucially involved in proliferative retinopathies, express and respond to HB-EGF. RPE cells express mRNAs for various members of the EGF-related growth factor family, among them for HB-EGF, as well as for the EGF receptors ErbB1, -2, -3, and -4. The gene expression of HB-EGF is stimulated in the presence of transforming and basic fibroblast growth factors and by oxidative stress and is suppressed during chemical hypoxia. Exogenous HB-EGF stimulates proliferation and migration of RPE cells and the gene and protein expression of the vascular endothelial growth factor (VEGF). HB-EGF activates at least three signal transduction pathways in RPE cells including the extracellular signal-regulated kinases (involved in the proliferation-stimulating action of HB-EGF), p38 (mediates the effects on chemotaxis and secretion of VEGF), and the phosphatidylinositol-3 kinase (necessary for the stimulation of chemotaxis). In epiretinal membranes of patients with proliferative retinopathies, HB-EGF immunoreactivity was partially colocalized with the RPE cell marker, cytokeratins; this observation suggests that RPE cell-derived HB-EGF may represent one factor that drives the uncontrolled wound-healing process of the retina. The stimulating effect on the secretion of VEGF may suggest that HB-EGF is also implicated in the pathological angiogenesis of the retina.

  9. Structure of peptidoglycan from Thermus thermophilus HB8.

    PubMed Central

    Quintela, J C; Pittenauer, E; Allmaier, G; Arán, V; de Pedro, M A

    1995-01-01

    The composition and structure of peptidoglycan (murein) extracted from the extreme thermophilic eubacterium Thermus thermophilus HB8 are presented. The structure of 29 muropeptides, accounting for more than 85% of total murein, is reported. The basic monomeric subunit consists of N-acetylglucosamine-N-acetylmuramic acid-L-Ala-D-Glu-L-Orn-D-Ala-D-Ala, acylated at the delta-NH2 group of Orn by a Gly-Gly dipeptide. In a significant proportion (about 23%) of total muropeptides, the N-terminal Gly is substituted by a residue of phenylacetic acid. This is the first time phenylacetic acid is described as a component of bacterial murein. Possible implications for murein physiology and biosynthesis are discussed. Murein cross-linking is mediated by D-Ala-Gly-Gly peptide cross-bridges. Glycan chains are apparently terminated by (1-->6) anhydro N-acetylmuramic acid residues. Neither reducing sugars nor murein-bound macromolecules were detected. Murein from T. thermophilus presents an intermediate complexity between those of gram-positive and gram-negative organisms. The murein composition and peptide cross-bridges of T. thermophilus are typical for a gram-positive bacterium. However, the murein content, degree of cross-linkage, and glycan chain length for T. thermophilus are closer to those for gram-negative organisms and could explain the gram-negative character of Thermus spp. PMID:7665471

  10. Spinal Hb9::Cre-derived excitatory interneurons contribute to rhythm generation in the mouse

    PubMed Central

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

    2017-01-01

    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-Vglut2Δ/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. PMID:28128321

  11. Identification and functional characterization of HbOsmotin from Hevea brasiliensis.

    PubMed

    Tong, Zheng; Sun, Yong; Wang, Dan; Wang, Limin; Li, Ling; Meng, Xueru; Feng, Weiqiang; Wurtele, Eve Syrkin; Wang, Xuchu

    2016-12-01

    Latex in the laticiferous cell network of Hevea brasiliensis tree is composed of cytoplasm that synthesizes natural rubber. Ethylene stimulation of the tree bark enhances latex production partly by prolonging the duration of latex flow during the tapping process. Here, we identified an osmotin-like cDNA sequence (HbOsmotin) from H. brasiliensis that belongs to the pathogenesis-related 5 (PR-5) gene family. The HbOsmotin protein is present in the lutoids of latex in H. brasiliensis, whereas in onion epidermal cells, this protein is predominantly distributed around the cell wall, suggesting that it may be secreted from the cytoplasm. We investigated the effects of exogenous ethylene on HbOsmotin transcription and protein accumulation in rubber latex, and further determined the protein function after osmotic stress in Arabidopsis. In regularly tapped trees, HbOsmotin expression was drastically inhibited in rubber latex after tapping, although the expression was subsequently recovered by ethylene stimulation. However, in virgin plants that had never been tapped, exogenous ethylene application slightly decreased HbOsmotin expression. HbOsmotin overexpression in Arabidopsis showed that HbOsmotin reduced the osmotic stress tolerance of the plant, which likely occurred by raising the water potential. These data indicated that HbOsmotin may contribute to osmotic regulation in laticiferous cells.

  12. GENERAL VIEW OF TYPE HB54s (BUILDINGS T1088 TO T1093) & ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    GENERAL VIEW OF TYPE HB-54s (BUILDINGS T-1088 TO T-1093) & CONVERTED TYPE HB-54S (BUILDINGS T-1094 TO T-1096), LOOKING SOUTHWEST; BUILDING T-1088 AT LEFT, BUILDING T-1096 AT RIGHT - Fort McCoy, Building No. T-1096, South side of South Ninth Avenue, Block 10, Sparta, Monroe County, WI

  13. Association of Genomic Instability with HbA1c levels and Medication in Diabetic Patients

    PubMed Central

    Grindel, Annemarie; Brath, Helmut; Nersesyan, Armen; Knasmueller, Siegfried; Wagner, Karl-Heinz

    2017-01-01

    Diabetes Mellitus type 2 (DM2) is associated with increased cancer risk. Instability of the genetic material plays a key role in the aetiology of human cancer. This study aimed to analyse genomic instability with the micronucleus cytome assay in exfoliated buccal cells depending on glycated haemoglobin (HbA1c) levels and medication in 146 female DM2 patients. The occurrence of micronuclei was significantly increased in DM2 patients compared to healthy controls. Furthermore, it was doubled in DM2 patients with HbA1c > 7.5% compared to subjects with HbA1c ≤ 7.5%. Positive correlations were found between micronuclei frequencies and HbA1c as well as fasting plasma glucose. Patients under insulin treatment showed a two-fold increase in micronuclei frequencies compared to subjects under first-line medication (no drugs or monotherapy with non-insulin medication). However, after separation of HbA1c (cut-off 7.5%) only patients with severe DM2 characterised by high HbA1c and insulin treatment showed higher micronuclei frequencies but not patients with insulin treatment and low HbA1c. We demonstrated that the severity of DM2 accompanied by elevated micronuclei frequencies predict a possible enhanced cancer risk among female DM2 patients. Therapy, therefore, should focus on a strict HbA1c control and personalised medical treatments. PMID:28150817

  14. Cutoff Point of HbA1c for Diagnosis of Diabetes Mellitus in Chinese Individuals

    PubMed Central

    Liu, Ming-Chuan; Li, Xin-Yu; Liu, Xu-Han; Feng, Qiu-Xia; Lu, Lu; Zhu, Zhu; Liu, Ying-Shu; Zhao, Wei; Gao, Zheng-Nan

    2016-01-01

    Background The purpose of the present study was to find the optimal threshold of glycated hemoglobin (HbA1c) for diagnosis of diabetes mellitus in Chinese individuals. Methods A total of 8 391 subjects (including 2 133 men and 6 258 women) aged 40–90 years with gradable retinal photographs were recruited. The relationship between HbA1c and diabetic retinopathy (DR) was examined. Receiver operating characteristic (ROC) curves were used to find the optimal threshold of HbA1c in screening DR and diagnosing diabetes. Results HbA1c values in patients with DR were significantly higher than in those with no DR. The ROC curve for HbA1c had an area under the curve of 0.881 (95%CI 0.857–0.905; P = 0.000). HbA1c at a cutoff of 6.5% had a high sensitivity (80.6%) and specificity (86.9%) for detecting DR. Conclusions HbA1c can be used to diagnose diabetes in a Chinese population, and the optimal HbA1c cutoff point for diagnosis is 6.5%. PMID:27861599

  15. Development of anti-HB-EGF immunoliposomes for the treatment of breast cancer.

    PubMed

    Nishikawa, Kaoru; Asai, Tomohiro; Shigematsu, Hirokazu; Shimizu, Kosuke; Kato, Hisakazu; Asano, Yoshihiro; Takashima, Seiji; Mekada, Eisuke; Oku, Naoto; Minamino, Tetsuo

    2012-06-10

    Increased expression of heparin-binding epidermal growth factor-like growth factor (HB-EGF) is frequently observed in certain cancers such as ovarian and breast cancers, and this protein is a desirable target for drug delivery by a drug delivery system (DDS). In the present study, we developed novel immunoliposomes targeting HB-EGF for cancer therapy. The immunoliposomes significantly associated with Vero-H cells overexpressing HB-EGF compared with their binding to wild-type Vero cells, whereas liposomes without modification by the antibody did not associate with either type of cells. Moreover, enhanced uptake of the immunoliposomes into Vero-H cells was observed as well as that into MDA-MB-231 human breast cancer cells, which are known to highly express HB-EGF. These results suggest that HB-EGF mediates the binding and uptake of the immunoliposomes in HB-EGF-expressing cells. Next, we determined the therapeutic effect of these immunoliposomes encapsulating an anticancer drug on tumor-bearing mice. For this purpose, we prepared doxorubicin (DOX)-encapsulated immunoliposomes and injected them intravenously into mice bearing MDA-MB-231 cancer cells. As a result, these DOX-encapsulated immunoliposomes suppressed not only tumor progression but also tumor regression. In conclusion, our results indicate that anti-HB-EGF antibody-modified liposomes could be a useful DDS carrier for the treatment of HB-EGF-expressing cancers.

  16. HB 1347 and Its Relationship to Foodservice Outsourcing in Illinois Public Schools

    ERIC Educational Resources Information Center

    Brashear, Gary L.

    2012-01-01

    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%…

  17. Markerless Gene Deletion with Cytosine Deaminase in Thermus thermophilus Strain HB27.

    PubMed

    Wang, Lei; Hoffmann, Jana; Watzlawick, Hildegard; Altenbuchner, Josef

    2015-12-11

    We developed a counterselectable deletion system for Thermus thermophilus HB27 based on cytosine deaminase (encoded by codA) from Thermaerobacter marianensis DSM 12885 and the sensitivity of T. thermophilus HB27 to the antimetabolite 5-fluorocytosine (5-FC). The deletion vector comprises the pUC18 origin of replication, a thermostable kanamycin resistance marker functional in T. thermophilus HB27, and codA under the control of a constitutive putative trehalose promoter from T. thermophilus HB27. The functionality of the system was demonstrated by deletion of the bglT gene, encoding a β-glycosidase, and three carotenoid biosynthesis genes, CYP175A1, crtY, and crtI, from the genome of T. thermophilus HB27.

  18. Quality of HbA1c Measurement in Trinidad and Tobago

    PubMed Central

    Rastogi, Maynika V.; Ladenson, Paul; Goldstein, David E.; Little, Randie R.

    2015-01-01

    Background: Monitoring of HbA1c is the standard of care to assess diabetes control. In Trinidad & Tobago (T&T) there are no existing data on the quality of HbA1c measurement. Our study examined the precision and accuracy of HbA1c testing in T&T. Methods: Sets of 10 samples containing blinded duplicates were shipped to laboratories in T&T. This exercise was repeated 6 months later. Precision and accuracy were estimated for each laboratory/method. Results: T&T methods included immunoassay, capillary electrophoresis, and boronate affinity binding. Most, but not all, laboratories demonstrated acceptable precision and accuracy. Conclusions: Continuous oversight of HbA1c testing (eg, through proficiency testing) in T&T is recommended. These results highlight the lack of oversight of HbA1c testing in some developing countries. PMID:26553021

  19. HbA(1c)--an analyte of increasing importance.

    PubMed

    Higgins, Trefor

    2012-09-01

    Since the incorporation in 1976 of HbA(1c) into a monitoring program of individuals with diabetes, this test has become the gold standard for assessment of glycemic control. Analytical methods have steadily improved in the past two decades, largely through the efforts of the National Glycohemoglobin Standardization program (NGSP). The new definition of HbA(1c) and the introduction of an analytically pure calibrator have increased the possibility for greater improvements in analytical performance. Controversies exist in the reporting of HbA(1c). The use of HbA(1c) has expanded beyond the use solely as a measure of glycemic control into a test for screening and diagnosing diabetes. With improvements in analytical performance, the effects of demographic factors such as age and ethnicity and clinical factors such as iron deficiency have been observed. In this review, the history, formation, analytical methods and parameters that affect HbA(1c) analysis are discussed.

  20. GM-CSF in sickle cell anemia patients with elevated Hb F.

    PubMed

    Haider, M Z; Raghupathy, R; Azizieh, F; Abdelsalam, R; D'Souza, T M; Adekile, A D

    2000-01-01

    We estimated plasma GM-CSF levels in a group of 28 steady-state sickle cell anemia (SS) patients in Kuwait, using an ELISA technique. There were 24 age-matched Hb AA controls, 14 of whom were healthy while 10 were acutely ill at the time of the study. Five SS patients were also studied during 6 episodes of painful crisis. Among the SS patients, 82.1% were homozygous for the Saudi Arabia/India (SAI) haplotype with Hb F ranging from 15 to 35% and total Hb from 8.5 to 11 g/dl. Three patients (siblings) were SAI/Benin compound heterozygotes with Hb F of 9-23% and total Hb >10 g/dl. One patient each was homozygous for the Benin or the Bantu haplotype; they had Hb F <2% and total Hb of 6.6 and 7.2 g/dl, respectively. Four (14. 3%) steady-state SS patients had detectable plasma GM-CSF ranging from 75 to 1,817.6 pg/ml. These included the 2 patients with Hb F <2. 0% and 2 with the SAI/Benin compound heterozygotes with Hb F of 11 and 9%, respectively. Four (66.7%) SS patients in crisis, 6 (42.9%) healthy controls and 6 (60%) acutely ill controls had detectable plasma GM-CSF. A clearcut association of GM-CSF with Hb F level or degree of anemia in steady-state SS patients could not be established. The appearance of GM-CSF in the plasma of patients in crisis and also among control subjects raises the possibility that other factors are involved in the production of this cytokine in the subjects studied.

  1. Development of an electrochemical immunosensor for the detection of HbA1c in serum.

    PubMed

    Liu, Guozhen; Khor, Sook Mei; Iyengar, Sridhar G; Gooding, J Justin

    2012-02-21

    An electrochemical immuno-biosensor for detecting glycosylated haemoglobin (HbA1c) is reported based on glassy carbon (GC) electrodes with a mixed layer of an oligo(phenylethynylene) molecular wire (MW) and an oligo(ethylene glycol) (OEG). The mixed layer is formed from in situ-generated aryl diazonium cations. To the distal end of the MW, a redox probe 1,1'-di(aminomethyl)ferrocene (FDMA) was attached followed by the covalent attachment of an epitope N-glycosylated pentapeptide (GPP), an analogon to HbA1c, to which an anti-HbA1c monocolonal antibody IgG can selectively bind. HbA1c was detected by a competitive inhibition assay based on the competition for binding to anti-HbA1c IgG antibodies between the analyte in solution, HbA1c, and the surface bound epitope GPP. Exposure of the GPP modified sensing interface to the mixture of anti-HbA1c IgG antibody and HbA1c results in the attenuation of ferrocene electrochemistry due to free antibody binding to the interface. Higher concentrations of analyte led to higher Faradaic currents as less anti-HbA1c IgG is available to bind to the electrode surface. It was observed that there is a good linear relationship between the relative Faradaic current of FDMA and the concentration of HbA1c from 4.5% to 15.1% of total haemoglobin in serum without the need for washing or rinsing steps.

  2. Three new alpha-globin variants: Hb Itapira [alpha30(B11)Glu-->Val (alpha1)], Hb Bom Jesus Da Lapa [alpha30(B11)Glu-->Ala (alpha1)] and Hb Boa Esperança [alpha16(A14)Lys-->Thr (alpha2)].

    PubMed

    Jorge, Susan E Costa; Kimura, Elza M; Oliveira, Denise M; Ogo, Satie; Albuquerque, Dulcinéia M; Costa, Fernando F; Sonati, Maria de Fátima

    2007-01-01

    Three novel alpha-globin variants were found during a screening program for hemoglobinopathies in blood donors at the UNICAMP Hematology and Hemotherapy Center, Campinas, State of São Paulo, Southeastern Brazil. They were named for the town of origin of the carrier as Hb Itapira [alpha30(B11)Glu-->Val], Hb Bom Jesus da Lapa [alpha30(B11)Glu-->Ala] and Hb Boa Esperança [alpha16(A14)Lys-->Thr]. Hb Itapira, like Hb Bom Jesus da Lapa, shows an electrophoretic mobility similar to that of Hb S [beta6(A3)GluVal, GAG-->GTG] at alkaline pH; it is associated with a triplicate alpha-globin allele (alphaalphaalpha(anti 3.7)) and corresponds to only 5.5% of the total hemoglobin (Hb). Hb Boa Esperança, found in two different individuals, moves faster than Hb A and exhibits an abnormal functional performance.

  3. Agitator Mixing Analysis in a HB-Line Flat Tank

    SciTech Connect

    Lee, S.Y.

    2002-07-31

    In support of the HB-Line Engineering agitator mixing project, flow pattern calculations have been made for a 45 degrees pitched three-blade agitator submerged in a flat rectangular tank. The work is intended to determine agitator speeds that provide acceptable mixing performance for various tank liquid levels based on flow rates past solids deposited on the bottom surface of the flat tank. The modeling results will help ensure the acceptable suspension of solid particles as a function of agitator speed and tank liquid level during precipitation operations. The numerical modeling and calculations have been performed using a computational fluid dynamics approach. Three-dimensional steady-state momentum and continuity equations were used as the basic equations to estimate fluid motion driven by an agitator with three 45 degrees pitched blades. Hydraulic conditions were fully turbulent (Reynolds number about 2x104). A standard two-equation turbulence model (k-e), was used to capture turbulent eddy motion. The commercial finite volume code, Fluent [7], was used to create a prototypic geometry file with a non-orthogonal mesh. Hybrid meshing was used to fill the computational region between the round-edged tank bottom and agitator regions. At high rotational speeds and low tank levels, a surface vortex can reach the agitator blades and allow air to be drawn into the solid-fluid mixing zone. This is not desirable in terms of mixing performance. The analysis results show that the lowest liquid level among the four considered, 4.5 inches, is higher than the critical liquid height for air entrainment for agitator speeds up to 600 rpm. All the analysis results demonstrate that about 600 rpm provides adequate solids mixing capability for various tank levels (12, 8.5, 7, and 4.5 inches) containing 20-micron solids with a specific gravity of 2.5.

  4. Challenges in HbA1c Analysis and Reporting in Patients with Variant Hemoglobins.

    PubMed

    Sultana, T A; Sheme, Z A; Sultana, G S; Sultana, B; Mishu, F A; Khan, N Z; Sarkar, B C; Muttalib, M A; Khan, S A; Choudhury, S; Mahtab, H

    2016-04-01

    Hemoglobin A1c (HbA(1)c) is a well-established indicator of mean glycemia. The presence of genetic variants of hemoglobin can profoundly affect the accuracy of HbA(1)c measurements. Variants of hemoglobin especially Hemoglobin E (HbE) is prevalent in South East Asia including Bangladesh. The objective of our study is to compare the HbA(1)c values measured on high performance liquid chromatography (HPLC) and Turbidimetric Inhibition Immunoassay (TINIA) in diabetic patients with variant hemoglobins including HbE. A total of 7595 diabetic patients receiving treatment at BIRDEM General Hospital were analyzed for HbA(1)c results within a period of two months from December 2013 to January 2014. Seventy two cases out of 7595 (0.95%) had either undetectable or below normal HbA(1)c levels (males-33 and females-39; ratio = 0.82:1) by HPLC method. In 34(0.45%) cases, HbA(1)c value was undetectable by HPLC method but was in the reportable range by TINIA method. In the other 38 (0.55%) cases, HbA(1)c levels were below the reportable range (<4%) by HPLC method but were in the normal or higher range by TINIA method. TINIA method did not agree with HPLC method on Bland Altman plot in the 38 cases with below normal HbA(1)c levels, [Mean bias -5.2(-9.3 to 1.0), 95% CI] but agreed very well [mean bias -0.21 (-0.84 to 0.42), y=1.1037+0.776X; r(2)=0.30, p<0.01] in controls. In control group mean MCV was 83.80±7.48 and in study group was 73.65±10.44. Alkaline electrophoresis confirmed the variant hemoglobin to be HbE. The fasting blood sugar levels of all the 72 cases correlated strongly with TINIA method (r(2) =0.75, p<0.0001) but not with HPLC (r = 0.24, p=0.13). In our regions where populations have a high prevalence of Hb variant, proper knowledge of hemoglobin variants which affect the measurements HbA(1)c level is essential. MCV of 80fl or below may serve as a rough guide to select samples that require analysis by TINIA method. Moreover, HPLC may be a convenient and inexpensive

  5. Luminol chemiluminescence biosensor for glycated hemoglobin (HbA1c) in human blood samples.

    PubMed

    Ahn, Kwang-Soo; Lee, JungHoon; Park, Jong-Myeon; Choi, Han Nim; Lee, Won-Yong

    2016-01-15

    Luminol chemiluminescence (CL) biosensor based on boronic acid modified gold substrate has been developed for the determination of glycated hemoglobin (HbA1c) in human blood samples. In order to selectively capture HbA1c in sample, carboxy-EG6-undecanethiol was self-assembled on a gold thin-film substrate, followed by covalent coupling of 3-aminophenyl boronic acid (3-APBA). The captured HbA1c containing four iron heme groups plays as a catalyst for luminol CL reaction in the presence of hydrogen peroxide, and thus the luminol CL response is linearly proportional to the amount of HbA1c captured on the biosensor surface. The present biosensor showed linear dynamic range of HbA1c from 2.5% to 17.0%, which well covers the clinically important concentration range. In addition, the present biosensor exhibited negligible response to interfering species such as hemoglobin, fructose, and sorbitol. The present HbA1c biosensor was applied to the determination of HbA1c in human blood samples and the results were well agreed with that obtained with a conventional method.

  6. Electrochemical sensor based on magnetic molecularly imprinted nanoparticles modified magnetic electrode for determination of Hb.

    PubMed

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

    2017-05-15

    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%.

  7. HB-EGF affects astrocyte morphology, proliferation, differentiation, and the expression of intermediate filament proteins.

    PubMed

    Puschmann, Till B; Zandén, Carl; Lebkuechner, Isabell; Philippot, Camille; de Pablo, Yolanda; Liu, Johan; Pekny, Milos

    2014-03-01

    Heparin-binding epidermal growth factor-like growth factor (HB-EGF), a vascular-derived trophic factor, belongs to the epidermal growth factor (EGF) family of neuroprotective, hypoxia-inducible proteins released by astrocytes in CNS injuries. It was suggested that HB-EGF can replace fetal calf serum (FCS) in astrocyte cultures. We previously demonstrated that in contrast to standard 2D cell culture systems, Bioactive3D culture system, when used with FCS, minimizes the baseline activation of astrocytes and preserves their complex morphology. Here, we show that HB-EGF induced EGF receptor (EGFR) activation by Y1068 phosphorylation, Mapk/Erk pathway activation, and led to an increase in cell proliferation, more prominent in Bioactive3D than in 2D cultures. HB-EGF changed morphology of 2D and Bioactive3D cultured astrocytes toward a radial glia-like phenotype and induced the expression of intermediate filament and progenitor cell marker protein nestin. Glial fibrillary acidic protein (GFAP) and vimentin protein expression was unaffected. RT-qPCR analysis demonstrated that HB-EGF affected the expression of Notch signaling pathway genes, implying a role for the Notch signaling in HB-EGF-mediated astrocyte response. HB-EGF can be used as a FCS replacement for astrocyte expansion and in vitro experimentation both in 2D and Bioactive3D culture systems; however, caution should be exercised since it appears to induce partial de-differentiation of astrocytes.

  8. HB-EGF is necessary and sufficient for Müller glia dedifferentiation and retina regeneration.

    PubMed

    Wan, Jin; Ramachandran, Rajesh; Goldman, Daniel

    2012-02-14

    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 pro-HB-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 pax6(b). We also uncover an HB-EGF/Ascl1a/Notch/hb-egf(a)-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.

  9. Influence of priming exercise on muscle deoxy[Hb + Mb] during ramp cycle exercise.

    PubMed

    Boone, Jan; Bouckaert, Jacques; Barstow, Thomas J; Bourgois, Jan

    2012-03-01

    The aim of the present study was to gain better insight into the mechanisms underpinning the sigmoid pattern of deoxy[Hb + Mb] during incremental exercise by assessing the changes in the profile following prior high-intensity exercise. Ten physically active students performed two incremental ramp (25 W min(-1)) exercises (AL and LL, respectively) preceded on one occasion by incremental arm (10 W min(-1)) and on another occasion by incremental leg exercise (25 W min(-1)), which served as the reference test (RT). Deoxy[Hb + Mb] was measured by means of near-infrared spectroscopy and surface EMG was recorded at the Vastus Lateralis throughout the exercises. Deoxy[Hb + Mb], integrated EMG and Median Power Frequency (MdPF) were expressed as a function of work rate (W) and compared between the exercises. During RT and AL deoxy[Hb + Mb] followed a sigmoid increase as a function of work rate. However, during LL deoxy[Hb + Mb] increased immediately from the onset of the ramp exercise and thus no longer followed a sigmoid pattern. This different pattern in deoxy[Hb + Mb] was accompanied by a steeper slope of the iEMG/W-relationship below the GET (LL: 0.89 ± 0.11% W(-1); RT: 0.74 ± 0.08% W(-1); AL: 0.72 ± 0.10% W(-1)) and a more pronounced decrease in MdPF in LL (17.2 ± 4.5%) compared to RT (5.0 ± 2.1%) and AL (3.9 ± 3.2%). It was observed that the sigmoid pattern of deoxy[Hb + Mb] was disturbed when the ramp exercise was preceded by priming leg exercise. Since the differences in deoxy[Hb + Mb] were accompanied by differences in EMG it can be suggested that muscle fibre recruitment is an important underlying mechanism for the pattern of deoxy[Hb + Mb] during ramp exercise.

  10. Electrochemical detection of HbA1c, a marker [correction of maker] for diabetes, using a flow immunoassay system.

    PubMed

    Tanaka, Tsuyoshi; Tsukube, Shoko; Izawa, Kojiro; Okochi, Mina; Lim, Tae-Kyu; Watanabe, Shugo; Harada, Manabu; Matsunaga, Tadashi

    2007-04-15

    An on-chip electrochemical flow immunoassay system for the detection of hemoglobin A1c (HbA1c) was developed using anti-human hemoglobin (Hb) IgG labeled with ferrocene monocarboxylic acid (Fc-COOH) and boronate-affinity chromatography. An on-chip column packed with boronate-activated agarose beads was used for the separation of HbA1c from both non-glycated Hb and free antibody. Anti-human Hb IgG conjugated to Fc-COOH (Fc-IgG) was used for the electrochemical detection of HbA1c. The assay procedure included immunoreactions with Fc-IgG and HbA1c, separation of immunocomplexes by boronate affinity, and electrochemical detection of Fc-IgG-HbA1c immunocomplexes. The immunoreaction mixtures were injected onto a boronate-affinity column. HbA1c-antibody complexes were then trapped onto the column by the affinity of HbA1c to boronic acid. Subsequently, elution buffer containing sorbitol was applied to elute HbA1c-antibody complexes and a current was detected by applying 600 mV versus Ag/AgCl. The elution signal was an estimation of the HbA1c amount. A linear correlation between the increase of current and HbA1c concentration was obtained up to an HbA1c concentration of 500 microg/ml. The HbA1c flow immunoassay was successfully achieved using hemolysates. This electrochemical flow immunoassay system enabled us to construct a novel point-of-care testing device for the monitoring of glycated proteins including HbA1c.

  11. 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.

    PubMed Central

    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

    2015-01-01

    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

  12. HbQ-India associated with microcytosis: An uncommon hemoglobin variant associated with a common hematologic condition.

    PubMed

    Kumar Yadav, Amit; Rusia, Usha

    2010-09-05

    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.

  13. DETAIL VIEW OF AP 93W, ROOF LEVEL, PLATFORM DSOUTH, HB3, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    DETAIL VIEW OF AP 93W, ROOF LEVEL, PLATFORM D-SOUTH, HB-3, FACING NORTHWEST - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

  14. A history of HbA1c through Clinical Chemistry and Laboratory Medicine.

    PubMed

    Gillery, Philippe

    2013-01-01

    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.

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

    PubMed Central

    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

    2016-01-01

    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

  16. Hb lepore/β0-thalassaemia with α+-thalassaemia interactions, a potential diagnostic pitfall.

    PubMed

    Alauddin, Hafiza; Mohamad Nasir, Suziana; Ahadon, Madzlifah; Raja Sabudin, Raja Zahratul Azma; Ithnin, Azlin; Hussin, Noor Hamidah; Alias, Hamidah; Loh, C-Khai; Abdul Latiff, Zarina; Abdul Murad, Nor Azian; Othman, Ainoon

    2015-12-01

    Haemoglobin (Hb) Lepore is a variant Hb consisting of two α-globin and two δβ-globin chains. In a heterozygote, it is associated with clinical findings of thalassaemia minor, but interactions with other haemoglobinopathies can lead to various clinical phenotypes and pose diagnostic challenges. We reported a pair of siblings from a Malay family, who presented with pallor and hepatosplenomegaly at the ages of 21 months and 14 months old. The red cell indices and peripheral blood smears of both patients showed features of thalassaemia intermedia. Other laboratory investigations of the patients showed conflicting results. However, laboratory investigation results of the parents had led to a presumptive diagnosis of compound heterozygote Hb Lepore/β-thalassaemia and co-inheritance α+-thalassaemia (-α3.7). Hb Lepore has rarely been detected in Southeast Asian countries, particularly in Malaysia. These two cases highlight the importance of family studies for accurate diagnosis, hence appropriate clinical management and genetic counseling.

  17. GENERAL VIEW OF NORTH VEHICLE ACCESS PLATFORMS, HB3, FACING NORTHEAST ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    GENERAL VIEW OF NORTH VEHICLE ACCESS PLATFORMS, HB-3, FACING NORTHEAST TOWARDS CEILING - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

  18. GENERAL VIEW OF VEHICLE ACCESS PLATFORM CNORTH, HB3, FACING NORTHWEST ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    GENERAL VIEW OF VEHICLE ACCESS PLATFORM C-NORTH, HB-3, FACING NORTHWEST - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

  19. GENERAL VIEW OF VEHICLE ACCESS PLATFORM ENORTH, HB3, FACING NORTH ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    GENERAL VIEW OF VEHICLE ACCESS PLATFORM E-NORTH, HB-3, FACING NORTH - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

  20. GENERAL VIEW OF VEHICLE ACCESS PLATFORM DNORTH, HB3, FACING NORTHWEST ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    GENERAL VIEW OF VEHICLE ACCESS PLATFORM D-NORTH, HB-3, FACING NORTHWEST - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

  1. GENERAL VIEW OF NORTH VEHICLE ACCESS PLATFORMS, HB3, FACING NORTH ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    GENERAL VIEW OF NORTH VEHICLE ACCESS PLATFORMS, HB-3, FACING NORTH TOWARDS FLOOR - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

  2. GENERAL VIEW OF VEHICLE ACCESS PLATFORM DNORTH, HB3, FACING NORTH ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    GENERAL VIEW OF VEHICLE ACCESS PLATFORM D-NORTH, HB-3, FACING NORTH - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

  3. GENERAL VIEW OF VEHICLE ACCESS PLATFORM CNORTH, HB3, FACING NORTHEAST ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    GENERAL VIEW OF VEHICLE ACCESS PLATFORM C-NORTH, HB-3, FACING NORTHEAST - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

  4. GENERAL VIEW OF VEHICLE ACCESS PLATFORM BNORTH, HB3, FACING NORTHEAST ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    GENERAL VIEW OF VEHICLE ACCESS PLATFORM B-NORTH, HB-3, FACING NORTHEAST - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

  5. GENERAL VIEW OF VEHICLE ACCESS PLATFORM BNORTH, HB3, FACING NORTH ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    GENERAL VIEW OF VEHICLE ACCESS PLATFORM B-NORTH, HB-3, FACING NORTH - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

  6. GENERAL VIEW OF VEHICLE ACCESS PLATFORM ENORTH, HB3, FACING NORTHWEST ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    GENERAL VIEW OF VEHICLE ACCESS PLATFORM E-NORTH, HB-3, FACING NORTHWEST - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

  7. The Role of β93 Cys in the Inhibition of Hb S Fiber Formation

    PubMed Central

    Knee, Kelly M.; Roden, Catherine K.; Flory, Mark R.; Mukerji, Ishita

    2016-01-01

    Recent studies have suggested that nitric oxide (NO) binding to hemoglobin (Hb) may lead to the inhibition of sickle cell fiber formation and the dissolution of sickle cell fibers. NO can react with Hb in at least 3 ways: 1) formation of Hb(II)NO, 2) formation of methemoglobin, and 3) formation of S-nitrosohemoglobin, through nitrosylation of the β93 Cys residue. In this study, the role of β93 Cys in the mechanism of sickle cell fiber inhibition is investigated through chemical modification with N-ethylmaleimide. UV resonance Raman, FT-IR and electrospray ionization mass spectroscopic methods in conjunction with equilibrium solubility and kinetic studies are used to characterize the effect of β93 Cys modification on Hb S fiber formation. Both FT-IR spectroscopy and electrospray mass spectrometry results demonstrate that modification can occur at both the β93 and α104 Cys residues under relatively mild reaction conditions. Equilibrium solubility measurements reveal that singly-modified Hb at the β93 position leads to increased amounts of fiber formation relative to unmodified or doubly-modified Hb S. Kinetic studies confirm that modification of only the β93 residue leads to a faster onset of polymerization. UV resonance Raman results indicate that modification of the α104 residue in addition to the β93 residue significantly perturbs the α1β2 interface, while modification of only β93 does not. These results in conjunction with the equilibrium solubility and kinetic measurements are suggestive that modification of the α104 Cys residue and not the β93 Cys residue leads to T-state destabilization and inhibition of fiber formation. These findings have implications for understanding the mechanism of NO binding to Hb and NO inhibition of Hb S fiber formation. PMID:17350155

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

    PubMed Central

    Chandrashekar, Vani

    2016-01-01

    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. PMID:26989559

  9. Extracellular Hb Enhances Cardiac Toxicity in Endotoxemic Guinea Pigs: Protective Role of Haptoglobin

    PubMed Central

    Baek, Jin Hyen; Zhang, Xiaoyuan; Williams, Matthew C.; Schaer, Dominik J.; Buehler, Paul W.; D’Agnillo, Felice

    2014-01-01

    Endotoxemia plays a major causative role in the myocardial injury and dysfunction associated with sepsis. Extracellular hemoglobin (Hb) has been shown to enhance the pathophysiology of endotoxemia. In the present study, we examined the myocardial pathophysiology in guinea pigs infused with lipopolysaccharide (LPS), a Gram-negative bacterial endotoxin, and purified Hb. We also examined whether the administration of the Hb scavenger haptoglobin (Hp) could protect against the effects observed. Here, we show that Hb infusion following LPS administration, but not either insult alone, increased myocardial iron deposition, heme oxygenase-1 expression, phagocyte activation and infiltration, as well as oxidative DNA damage and apoptosis assessed by 8-hydroxy-2'-deoxyguanosine (8-OHdG) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) immunostaining, respectively. Co-administration of Hp significantly attenuated the myocardial events induced by the combination of LPS and Hb. These findings may have relevant therapeutic implications for the management of sepsis during concomitant disease or clinical interventions associated with the increased co-exposures to LPS and Hb, such as trauma, surgery or massive blood transfusions. PMID:24691127

  10. Significance of HbA1c Test in Diagnosis and Prognosis of Diabetic Patients

    PubMed Central

    Sherwani, Shariq I.; Khan, Haseeb A.; Ekhzaimy, Aishah; Masood, Afshan; Sakharkar, Meena K.

    2016-01-01

    Diabetes is a global endemic with rapidly increasing prevalence in both developing and developed countries. The American Diabetes Association has recommended glycated hemoglobin (HbA1c) as a possible substitute to fasting blood glucose for diagnosis of diabetes. HbA1c is an important indicator of long-term glycemic control with the ability to reflect the cumulative glycemic history of the preceding two to three months. HbA1c not only provides a reliable measure of chronic hyperglycemia but also correlates well with the risk of long-term diabetes complications. Elevated HbA1c has also been regarded as an independent risk factor for coronary heart disease and stroke in subjects with or without diabetes. The valuable information provided by a single HbA1c test has rendered it as a reliable biomarker for the diagnosis and prognosis of diabetes. This review highlights the role of HbA1c in diagnosis and prognosis of diabetes patients. PMID:27398023

  11. Targeting autocrine HB-EGF signaling with specific ADAM12 inhibition using recombinant ADAM12 prodomain

    PubMed Central

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

    2015-01-01

    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

  12. Targeting autocrine HB-EGF signaling with specific ADAM12 inhibition using recombinant ADAM12 prodomain.

    PubMed

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

    2015-10-19

    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.

  13. Targeting autocrine HB-EGF signaling with specific ADAM12 inhibition using recombinant ADAM12 prodomain

    NASA Astrophysics Data System (ADS)

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

    2015-10-01

    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.

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

    PubMed

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

    2016-01-01

    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.

  15. Screening for co-existence of α-thalassemia in β-thalassemia and in HbE heterozygotes via an enzyme-linked immunosorbent assay for Hb Bart's and embryonic ζ-globin chain.

    PubMed

    Tatu, Thanusak; Kiewkarnkha, Tiemjan; Khuntarak, Surakit; Khamrin, Sakdinan; Suwannasin, Surasit; Kasinrerk, Watchara

    2012-04-01

    We sought to demonstrate the ability of levels of Hb Bart's and ζ-globin chain quantified by enzyme-linked immunosorbent assay (ELISA) in detecting α-thalassemia in β-thalassemia and HbE heterozygotes. We developed an in-house sandwich ELISA method using monoclonal antibodies (mAbs) to Hb Bart's and ζ-globin chain, and quantified levels of Hb Bart's and ζ-globin chain in 172 and 223 anonymous blood samples of β-thalassemia and HbE heterozygotes, respectively. Genotypes of α-thalassemia 1, β-thalassemia were identified, and HbE allele was confirmed using a newly developed multiplex allele-specific PCR. The in-house sandwich ELISA method detected Hb Bart's in 6.4% of β-thalassemia heterozygotes, of which 5.2% showed detectable amounts of the ζ-globin chain. 15.2% of individuals heterozygous for HbE showed a detectable amount of Hb Bart's, and the ζ-globin chain was detected in 11.2% of this cohort. All samples having detectable amounts of Hb Bart's and the ζ-globin chain were verified to be SEA-type α-thalassemia 1. ELISA-quantified Hb Bart's and ζ-globin chain levels can be used to detect double heterozygosity of α- and β-thalassemia and of α-thalassemia and HbE. This strategy may be useful in screening for co-existence of α-thalassemia in β-thalassemia and in HbE heterozygotes, particularly in countries where α-, β-thalassemia and HbE are endemic.

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

    PubMed

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

    2016-12-01

    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, P<0·05) in both groups. Fruit juice intake was reduced (approximately 1 serving/week, P=0·029) in the first group. In all, twenty participants (71·4 %) experienced a decrease (n 15) or no change (n 5) in HbA1c (range 0-4 mmol/mol), whereas eight participants experienced an increase in HbA1c (range 0·5-2·5 mmol/mol). There was high compliance with the healthier snack 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.

  17. The impact of the HbA1c level of type 2 diabetics on the structure of haemoglobin

    PubMed Central

    Ye, Shaoying; Ruan, Ping; Yong, Junguang; Shen, Hongtao; Liao, Zhihong; Dong, Xiaolei

    2016-01-01

    This study explores the impact of HbA1c levels on the structure of haemoglobin (Hb) in patients with type 2 diabetes. Seventy-four diabetic patients were classified into the following two groups based on their level of HbA1c: group A, patients with good glycaemic control (HbA1c < 7.0%, n = 36); group B, patients with persistent hyperglycaemia (HbA1c ≥ 9.0%, n = 38). Thirty-four healthy people served as controls (group H). Hb structure was examined by Fourier transform infrared spectroscopy (FTIR), and diabetic erythrocytes were modelled to estimate the impact of glucose on these cells and Hb. Increasing glucose concentrations altered both erythrocyte parameters and the Hb secondary structure. Group B differed significantly from group H (p < 0.05): in the former, the ordered Hb secondary structure had a strong tendency to transform into a disordered secondary structure, decreasing structural stability. We presumed here that high HbA1c levels might be a factor contributing to Hb structural modifications in diabetic patients. FTIR spectral analysis can provide a novel way to investigate the pathogenesis of type 2 diabetes mellitus. PMID:27624402

  18. 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].

    PubMed

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

    2015-01-01

    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.

  19. What is the Role of HbA1c in Diabetic Hemodialysis Patients?

    PubMed

    Coelho, Silvia

    2016-01-01

    The definition of a good glycemic control in patients with diabetes mellitus on hemodialysis is far from settled. In the general population, hemoglobin A1c is highly correlated with the average glycemia of the last 8-12 weeks. However, in hemodialysis patients, the correlation of hbA1c with glycemia is weaker as it also reflects changes in hemoglobin characteristics and red blood cells half-life. As expected, studies show that the association between HbA1c and outcomes in these patients differ from the general population. Therefore, the value of HbA1c in the treatment of hemodialysis patients has been questioned. Guidelines are generally cautious in their recommendations about possible targets of HbA1c in this population. Indeed, the risk of not treating hyperglycemia should be weighed against the particularly high risk of precipitating hypoglycemia in dialysis patients. In this review, a critical analysis of the current role of HbA1c in the care of hemodialysis patients is presented.

  20. Coacervate delivery of HB-EGF accelerates healing of type 2 diabetic wounds.

    PubMed

    Johnson, Noah R; Wang, Yadong

    2015-01-01

    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.

  1. Excess HB-EGF, which promotes VEGF signaling, leads to hydrocephalus

    PubMed Central

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

    2016-01-01

    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

  2. Roles of poly(3-hydroxybutyrate) depolymerase and 3HB-oligomer hydrolase in bacterial PHB metabolism.

    PubMed

    Sugiyama, Akinori; Kobayashi, Teruyuki; Shiraki, Mari; Saito, Terumi

    2004-06-01

    Many poly-3-hydroxybutyrate (PHB)-degrading enzymes have been studied. But biological roles of 3HB-oligomer hydrolases (3HBOHs) and how PHB depolymerases (PHBDPs) and 3HBOHs cooperate in PHB metabolism are not fully elucidated. In this study, several PHBDPs and 3HBOHs from three types of bacteria were purified, and their substrate specificity, kinetic properties, and degradation products were investigated. From the results, PHBDP and 3HBOH seemed to play a role in PHB metabolism in three types of bacteria, as follows: (A) In Ralstonia pickettii T1, an extracellular PHBDP degrades extracellular PHB to various-sized 3HB-oligomers, which an extracellular 3HBOH hydrolyzes to 3HB-monomers. (B) In Acidovorax sp. SA1, an extracellular PHBDP hydrolyzes extracellular PHB to small 3HB-oligomers (dimer and trimer), which an intracellular 3HBOH efficiently degrades to 3HB in the cell. (C) In Ralstonia eutropha H16, an intracellular 3HBOH helps in the degradation of intracellular PHB inclusions by PHBDP.

  3. An integrated framework for joint HRF and drift estimation and HbO/HbR signal improvement in fNIRS data.

    PubMed

    Shah, Adnan; Seghouane, Abd-Krim

    2014-11-01

    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.

  4. 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

    PubMed Central

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

    2016-01-01

    Introduction 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. Materials and methods 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). Results 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. Conclusions The four HbA1c methods commonly used with commercial analyzers showed a good reliability and comparability, although some interference may falsely alter the result. PMID:27812304

  5. The kinematics of the high velocity bipolar nebulae NGC 6537 and HB 5

    NASA Astrophysics Data System (ADS)

    Corradi, Romano L. M.; Schwarz, Hugo E.

    1993-03-01

    The velocity structure of the bipolar planetary nebulae (PNe) NGC 6537 and Hb 5 has been investigated by means of medium dispersion long slit spectra. We have derived kinematical parameters and the deprojected shapes of the two nebulae by applying the kinematical model introduced by Solf and Ulrich (1985). In the direction of the polar axis of the nebulae, the deprojected expansion velocity is computed to be 300 km/s for NGC 6537 and about 250 km/s for Hb 5. These are very high velocities, but not unusual in the class of bipolar nebulae. The observed shapes and the velocity fields, in particular the one of Hb 5, are nicely reproduced by the interacting winds models by Icke et al. (1989). These imply a strongly aspherical initial mass distribution, i.e. equatorial to polar density contrasts larger than five. We espouse the idea that these initial conditions are created in interacting binary systems.

  6. PEGYLATION OF αα-Hb USING SUCCINIMIDYL PROPIONIC ACID PEG 5K

    PubMed Central

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

    2014-01-01

    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

  7. Independent association of HbA(1c) and incident cardiovascular disease in people without diabetes.

    PubMed

    Adams, Robert J; Appleton, Sarah L; Hill, Catherine L; Wilson, David H; Taylor, Anne W; Chittleborough, Catherine R; Gill, Tiffany K; Ruffin, Richard E

    2009-03-01

    Recent studies have reported no association between elevated glycated hemoglobin (HbA(1c)) and incident cardiovascular disease (CVD) among women without diabetes. This study describes associations between HbA(1c) and new onset CVD in a representative adult population cohort. Assessment of participants in The North West Adelaide Health Study (NWAHS), a population study of randomly selected adults (age > or =18 years, n = 4,060), included measurement of height, weight, blood pressure, fasting lipids, glucose, and HbA(1c). A self-completed questionnaire assessed doctor-diagnosed diabetes, CVD and stroke, smoking status, and demographics. The cohort was followed for an average 3.5 years. Of the 2,913 adults free of diabetes at baseline and follow-up, 94 (3.5%) reported new onset coronary heart disease (CHD) and/or stroke. Compared with those with an HbA(1c) < or =5.0%, risk of new onset CVD was increased in those with HbA(1c) 5.4-5.6% (odds ratio (OR) 2.5, 95% confidence interval (CI) 1.4, 4.6), and > or =5.7% (OR 1.9, 95% CI 1.1, 3.4), after adjustment for other risk factors. The association was stronger in women than men (P = 0.03), and attenuated to only a small degree by addition of impaired fasting glucose (IFG), hypertension, hypercholesterolemia, BMI, waist circumference, or smoking to the model. Elevated HbA(1c) is related to new onset CVD over a relatively short follow-up period in both men and women without diabetes and who do not develop diabetes, after adjustment for other major risk factors. Unlike previous studies, this relationship was not substantially attenuated by other traditional risk factors.

  8. BCL11A IS A MAJOR HbF QUANTITATIVE TRAIT LOCUS IN THREE DIFFERENT POPULATIONS WITH β-HEMOGLOBINOPATHIES

    PubMed Central

    Sebastiani, Paola; So, Jason C.C.; Ma, Edmond S.K.; Chan, Li Chong; Fucharoen, Goonnapa; Fucharoen, Supan; Barbosa, Cynara G.; Vardarajan, Badri N.; Farrer, Lindsay A.; Baldwin, Clinton T.; Steinberg, Martin H.; Chui, David H.K.

    2014-01-01

    Increased HbF levels or F-cell (HbF containing erythrocyte) numbers can ameliorate the disease severity of β-thalassemia major and sickle cell anemia. Recent genome wide association studies reported that single nucleotide polymorphisms (SNPs) in BCL11A gene on chromosome 2p16.1 were correlated with F-cells among healthy northern Europeans, and HbF among Sardinians with β-thalassemias. In this study, we showed that SNPs in BCL11A were associated with F-cell numbers in Chinese with β-thalassemia trait, and with HbF levels in Thais with either β-thalassemia or HbE trait and in African Americans with sickle cell anemia. Taken together, the data suggest that the functional motifs responsible for modulating F-cells and HbF levels reside within a 3 kb region in the second intron of BCL11A. PMID:18691915

  9. Small angle neutron scattering studies of HbA in concentrated solutions.

    PubMed Central

    Krueger, S; Chen, S H; Hofrichter, J; Nossal, R

    1990-01-01

    Differential cross-sections for neutrons scattered by normal human hemoglobin have been determined over the range of concentrations from 2 to approximately 35 weight percent. Data are compared with structure factors calculated from models of monodisperse hard spheres interacting through a screened Coulomb potential. Good agreement is noted when the volume fraction eta is adjusted during multivariate fitting of data, but the fitted value of eta is always lower than expected from the known Hb concentration of the samples. Calculations of cross-sections for polydisperse scatterers suggest that the samples may contain oligomers of the fundamental tetrameric Hb molecule. PMID:2207261

  10. [Biochemical and clinical studies of 2 new Italian cases of Hb G-Ferrara heterozygosis].

    PubMed

    Guerrasio, A; Saglio, G; Camaschella, C; Pich, P G; Barberis, E; Del Ponte, D; Izzo, P

    1979-05-30

    The Authors report the data concerning a family coming from Ficarolo (Rovigo). The father and one son were found hematologically healthy, but resulted carriers of Hb G-Ferrara. This is an unstable rare pigment with a replacement in the beta 57 (E-1) helicoidal position. The type and site of the mutation explain the "in vitro" molecular instability; on the other hand, this latter doesn't seem to cause any hematological disorder, even if an increased met-Hb production was found when affected blood was incubated at 37 degrees C for two hours in sterile conditions.

  11. HbA1c as a Diagnostic Test for Diabetes Mellitus – Reviewing the Evidence

    PubMed Central

    Florkowski, Chris

    2013-01-01

    The evidence base in support of HbA1c as a diagnostic test for diabetes mellitus is focused on predicting a clinical outcome, considered to be the pinnacle of the Stockholm Hierarchy applied to reference intervals and clinical decision limits. In the case of diabetes, the major outcome of interest is the long term microvascular complications for which a large body of data has been accumulated, leading to the endorsement of HbA1c for diagnosis in many countries worldwide, with some variations in cut-offs and testing strategies. PMID:24151343

  12. Poly-4-hydroxybutyrate (P4HB): a new generation of resorbable medical devices for tissue repair and regeneration.

    PubMed

    Williams, Simon F; Rizk, Said; Martin, David P

    2013-10-01

    Poly-4-hydroxybutyrate (P4HB) is a thermoplastic, linear polyester, produced by recombinant fermentation, that can be converted into a wide range of resorbable medical devices. P4HB fibers are exceptionally strong, and can be designed to provide prolonged strength retention in vivo. In 2007, the FDA cleared a monofilament suture made from P4HB for general soft tissue approximation and/or ligation. Subsequently, surgical mesh devices for hernia repair, tendon and ligament repair, and plastic and reconstructive surgery have been introduced for clinical use. This review describes the unique properties of P4HB, its clinical applications, and potential uses that are under development.

  13. Antibacterial activity of a modified unfilled resin containing a novel polymerizable quaternary ammonium salt MAE-HB

    PubMed Central

    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

    2016-01-01

    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). The growth inhibitory effect was independent of the incubation time (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 < 0.05). These data indicate that incorporation of MAE-HB confers unfilled resin with strong and long-lasting antibacterial effects against S. mutans. PMID:27659279

  14. A case of hemoglobin Hiroshima (β146 histidine to aspartic acid) with compensatory erythremia and undetectable HbA₁c.

    PubMed

    Nishimori, Hisakazu; Harano, Keiko; Wada, Hideho; Takano, Satoshi; Fukuda, Shinji; Takehara, Yukihito; Matsumoto, Hiroshi; Kumagai, Isao; Tanimoto, Mitsune; Takeda, Sho

    2012-06-01

    Hemoglobin (Hb) Hiroshima is an Hb variant that travels rapidly on electrophoresis and shows a fourfold increase in oxygen affinity and a decreased Bohr effect. We encountered a 40-year-old male patient with erythremia and an undetectable HbA(1c) level. The presence of an abnormal hemoglobin molecule was suggested by the results of high-performance liquid chromatography analysis. Subsequent gene analysis by direct sequencing confirmed Hb Hiroshima (β146 histidine → aspartic acid). Caution should be exercised when diagnosing erythremia.

  15. Hb A1c Determination by Capillary Electrophoresis is an Efficient Method for Detecting β-Thalassemias and Hemoglobin Variants.

    PubMed

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

    2016-09-01

    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.

  16. A NIR Flare of the QSO [HB89] 0234+285

    NASA Astrophysics Data System (ADS)

    Carrasco, L.; Porras, A.; Recillas, E.; Chavushyan, V.; Mayya, D. Y.

    2017-02-01

    We report on the recent NIR flare of the high redshift QSO (z=1.213) [hb89]0234+285 also known as BZQJ0237+2848, cross correlated with the radio source 4C+28.07 and the Gamma-ray source 2FGLJ0237.4+2846.

  17. A successful twin pregnancy in a patient with HbE-β-thalassemia in western India.

    PubMed

    Merchant, R; Italia, K; Ahmed, J; Ghosh, K; Colah, R B

    2015-01-01

    Improvements in medical facilities have helped a large number of clinically severe hemoglobin E (HbE)-β-thalassemia patients reach adulthood. Consequently, there is a new challenge, that of managing women with HbE-β-thalassemia during pregnancy. In particular, they have a high risk of abortion, preterm delivery, intrauterine growth restriction, and thromboembolism. A 27-year-old HbE-β-thalassemia patient on regular transfusion, who was splenectomized and heptatitis C (HCV)-positive, conceived for the first time without any infertility treatment. However, there was incomplete abortion with heavy bleeding at 3 months of gestation, which required bilateral uterine artery angiography. The angiogram showed the left uterine artery to be moderately hypertrophied. This was embolized with 300-500 micron polyvinyl alcohol (PVA) to stop the bleeding. Soon after, she conceived again with a twin pregnancy, and at 33.3 weeks of gestation, there was a normal delivery of twin girls without any postpartum hemorrhage or perineal tear. Both babies were given prematurity care. The mother and children were both normal up till the last follow-up 18 months after delivery, and both the girls are HbE heterozygous. Thorough monitoring of endocrine functions along with proper management of transfusions and iron overload can help in reducing the complications related to pregnancy in these patients.

  18. STS-33: At Pad B - IEA Removal; STS-32: In the VAB HB1 - IEA Removal

    NASA Technical Reports Server (NTRS)

    1989-01-01

    The STS-33 at Pad B Integrated Electronic Assembly (I.E.A.) is shown. The STS-32 I.E.A. removal in the Vehicle Assembly Building (V.A.B) High Bay 1 (H.B.1) is also presented. The change out of the short they found in boosters is the purpose for the video.

  19. LSST camera grid structure made out of ceramic composite material, HB-Cesic

    NASA Astrophysics Data System (ADS)

    Kroedel, Matthias R.; Langton, J. Bryan

    2016-08-01

    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.

  20. HB-EGF directs stromal cell polyploidy and decidualization via cyclin D3 during implantation.

    PubMed

    Tan, Yi; Li, Meiling; Cox, Sandra; Davis, Marilyn K; Tawfik, Ossama; Paria, Bibhash C; Das, Sanjoy K

    2004-01-01

    Stromal cell polyploidy is a unique phenomenon that occurs during uterine decidualization following embryo implantation, although the developmental mechanism still remains elusive. The general consensus is that the aberrant expression and altered functional activity of cell cycle regulatory molecules at two particular checkpoints G1 to S and G2 to M in the cell cycle play an important role in the development of cellular polyploidy. Despite the compelling evidence of intrinsic cell cycle alteration, it has been implicated that the development of cellular polyploidy may be controlled by specific actions of extracellular growth regulators. Here we show a novel role for heparin-binding EGF-like growth factor (HB-EGF) in the developmental process of stromal cell polyploidy in mice. HB-EGF, which is one of the earliest known molecular mediators of implantation in mice and humans, promotes stromal cell polyploidy via upregulation of cyclin D3. Adenoviral delivery of antisense cyclin D3 attenuates cyclin D3 expression and abrogates HB-EGF-induced stromal cell polyploidy in vitro and in vivo. Collectively, the results demonstrate that the regulation of stromal cell polyploidy and decidualization induced by HB-EGF depend on cyclin D3 induction.

  1. VIEW OF HB1 (VAB HIGH BAY) WITH MOBILE LAUNCHER PLATFORM ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    VIEW OF HB-1 (VAB HIGH BAY) WITH MOBILE LAUNCHER PLATFORM (VEHICLE ACCESS PLATFORMS ARE VISIBLE IN THE CENTER), FACING WEST - Cape Canaveral Air Force Station, Launch Complex 39, Vehicle Assembly Building, VAB Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

  2. Replacement of PBNA in HB and HC polymers used in SRM propellant and liner

    NASA Technical Reports Server (NTRS)

    Levinthal, M. L.; Law, R. D.; Suisse, D. C.

    1981-01-01

    The antioxidant phenyl-beta-naphthylamine (PBNA) was used in both HB and HC polymers. The sole (domestic) supplier of PBNA has withdrawn this product from the market, primarily because of suspected health hazards. Commercially available substitute(s) were selected and qualified for use in the two polymers.

  3. TGF{beta} induces proHB-EGF shedding and EGFR transactivation through ADAM activation in gastric cancer cells

    SciTech Connect

    Ebi, Masahide; Kataoka, Hiromi; Shimura, Takaya; Kubota, Eiji; Hirata, Yoshikazu; Mizushima, Takashi; Mizoshita, Tsutomu; Tanaka, Mamoru; Mabuchi, Motoshi; Tsukamoto, Hironobu; Tanida, Satoshi; Kamiya, Takeshi; Higashiyama, Shigeki; Joh, Takashi

    2010-11-19

    Research highlights: {yields} TGF{beta} induces EGFR transactivation through proHB-EGF shedding by activated ADAM members in gastric cancer cells. {yields} TGF{beta} induces nuclear translocation of HB-EGF-CTF cleaved by ADAM members. {yields} TGF{beta} enhances cell growth by EGFR transactivation and HB-EGF-CTF nuclear translocation and ADAM inhibitors block these effects. {yields} Silencing of ADAM17 also blocks EGFR transactivation, HB-EGF-CTF nuclear translocation and cancer cell growth by TGF{beta}. {yields} ADAM17 may play a crucial role in this TGF{beta}-HB-EGF signal transduction. -- Abstract: Background and aims: Transforming growth factor-beta (TGF{beta}) is known to potently inhibit cell growth. Loss of responsiveness to TGF{beta} inhibition on cell growth is a hallmark of many types of cancer, yet its mechanism is not fully understood. Membrane-anchored heparin-binding EGF-like growth factor (proHB-EGF) ectodomain is cleaved by a disintegrin and metalloproteinase (ADAM) members and is implicated in epidermal growth factor receptor (EGFR) transactivation. Recently, nuclear translocation of the C-terminal fragment (CTF) of pro-HB-EGF was found to induce cell growth. We investigated the association between TGF{beta} and HB-EGF signal transduction via ADAM activation. Materials and methods: The CCK-8 assay in two gastric cancer cell lines was used to determine the effect for cell growth by TGF{beta}. The effect of two ADAM inhibitors was also evaluated. Induction of EGFR phosphorylation by TGF{beta} was analyzed and the effect of the ADAM inhibitors was also examined. Nuclear translocation of HB-EGF-CTF by shedding through ADAM activated by TGF{beta} was also analyzed. EGFR transactivation, HB-EGF-CTF nuclear translocation, and cell growth were examined under the condition of ADAM17 knockdown. Result: TGF{beta}-induced EGFR phosphorylation of which ADAM inhibitors were able to inhibit. TGF{beta} induced shedding of proHB-EGF allowing HB-EGF-CTF to

  4. 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).

    PubMed

    Boucher, Maria O; Chui, David H K; Woda, Bruce A; Newburger, Peter E

    2016-06-01

    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.

  5. Secretion of IL-13 by airway epithelial cells enhances epithelial repair via HB-EGF.

    PubMed

    Allahverdian, Sima; Harada, Norihiro; Singhera, Gurpreet K; Knight, Darryl A; Dorscheid, Delbert R

    2008-02-01

    Inappropriate repair after injury to the epithelium generates persistent activation, which may contribute to airway remodeling. In the present study we hypothesized that IL-13 is a normal mediator of airway epithelial repair. Mechanical injury of confluent airway epithelial cell (AEC) monolayers induced expression and release of IL-13 in a time-dependent manner coordinate with repair. Neutralizing of IL-13 secreted from injured epithelial cells by shIL-13Ralpha2.FC significantly reduced epithelial repair. Moreover, exogenous IL-13 enhanced epithelial repair and induced epidermal growth factor receptor (EGFR) phosphorylation. We examined secretion of two EGFR ligands, epidermal growth factor (EGF) and heparin-binding EGF (HB-EGF), after mechanical injury. Our data showed a sequential release of the EGF and HB-EGF by AEC after injury. Interestingly, we found that IL-13 induces HB-EGF, but not EGF, synthesis and release from AEC. IL-13-induced EGFR phosphorylation and the IL-13-reparative effect on AEC are mediated via HB-EGF. Finally, we demonstrated that inhibition of EGFR tyrosine kinase activity by tyrphostin AG1478 increases IL-13 release after injury, suggesting negative feedback between EGFR and IL-13 during repair. Our data, for the first time, showed that IL-13 plays an important role in epithelial repair, and that its effect is mediated through the autocrine release of HB-EGF and activation of EGFR. Dysregulation of EGFR phosphorylation may contribute to a persistent repair phenotype and chronically increased IL-13 release, and in turn result in airway remodeling.

  6. Quantitative measurement of HbA1c by an immunoturbidimetric assay compared to a standard HPLC method.

    PubMed

    Hamwi, A; Schweiger, C R; Veitl, M; Schmid, R

    1995-07-01

    Determination of hemoglobin A1c (HbA1c) is one of the most important monitoring procedures for long-term control of diabetes mellitus. Several analytical methods have been developed for the measurement of glycohemoglobin (GHb). Those most frequently used are ion-exchange chromatography for HbA1c and affinity chromatography for total GHb. In this study, a new turbidimetric immunoassay for HbA1c (Boehringer Mannheim, Germany) was evaluated that was performed on a Hitachi 911 clinical chemistry analyzer (Boehringer Mannheim). Good linearity in the range of 5% to 15% HbA1c, within-run and between-run coefficients of variation ranging from 2.4% to 5.9% were obtained. Results of 179 diabetic and nondiabetic patients showed good correlation to those of a routine HPLC method (r = 0.96). In addition, HbA2, HbS, and HbF in samples from nondiabetic patients were not detected by the immunoturbimetric assay and the "labile" HbA1c fraction (Schiff base) did not interfere with the new test.

  7. 76 FR 66333 - Carolina Power & Light Company, H.B. Robinson Steam Electric Plant, Unit No. 2; Environmental...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-26

    ... through the ``Generic Environmental Impact Statement for License Renewal of Nuclear Plants: H.B. Robinson... COMMISSION Carolina Power & Light Company, H.B. Robinson Steam Electric Plant, Unit No. 2; Environmental... operation of the H. B. Robinson Steam Electric Plant, Unit 2 (HBRSEP), located in Darlington County,...

  8. Mild pyrolysis of P3HB/Switchgrass blends for the production of bio-oil enriched with crotonic acid

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The mild pyrolysis of switchgrass/poly-3-hydroxybutyrate (P3HB) blends that mimic P3HB-producing switchgrass lines was studied in a pilot scale fluidized bed reactor with the goal of simultaneously producing crotonic acid and switchgrass-based bio-oil. Factors such as pyrolysis temperature, residenc...

  9. Structural basis for the antipolymer activity of Hb ζ2βs2 trapped in a tense conformation

    NASA Astrophysics Data System (ADS)

    Safo, Martin K.; Ko, Tzu-Ping; Schreiter, Eric R.; Eric Russell, J.

    2015-11-01

    The phenotypical severity of sickle cell disease (SCD) can be mitigated by modifying mutant hemoglobin S (Hb s, Hb α2β 2s) to contain embryonic ζ globin in place of adult α-globin subunits (Hb ζ2β2s). Crystallographical analyses of liganded Hb ζζ2β2s, 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 βs subunits of T-state deoxyHb α2β2s and T-state CO-liganded Hb ζ2β2s reveal significant displacements of both mutant βsVal6 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 ζ2βs2 additionally exhibits a unique trimer-of-heterotetramers crystal packing that is sustained by novel intermolecular interactions involving the pathological βsVal6, contrasting sharply with the classical double-stranded packing of deoxyHb S. Finally, the unusually large buried solvent-accessible surface area for CO-Hb ζ2β2s suggests that it does not co-assemble with deoxyHb S in vivo. In sum, the antipolymer activities of Hb ζ203b2;2s appear to arise from both repositioning and replacement of specific α- and βs-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 ζ2β2s, and recommend the utility of SCD therapeutics that capitalize on α-globin exchange strategies.

  10. Molecular concentration of deoxyHb in human prefrontal cortex predicts the emergence and suppression of consciousness.

    PubMed

    Leon-Dominguez, Umberto; Izzetoglu, Meltem; Leon-Carrion, Jose; Solís-Marcos, Ignacio; Garcia-Torrado, Francisco Jose; Forastero-Rodríguez, Ana; Mellado-Miras, Patricia; Villegas-Duque, Diego; Lopez-Romero, Juan Luis; Onaral, Banu; Izzetoglu, Kurtulus

    2014-01-15

    This is the first study to use fNIRS to explore anaesthetic depth and awakening during surgery with general anaesthesia. A 16 channel continuous wave (CW) functional near-infrared system (fNIRS) was used to monitor PFC activity. These outcomes were compared to BIS measures. The results indicate that deoxyHb concentration in the PFC varies during the suppression and emergence of consciousness. During suppression, deoxyHb levels increase, signalling the deactivation of the PFC, while during emergence, deoxyHb concentration drops, initiating PFC activation and the recovery of consciousness. Furthermore, BIS and deoxyHb concentrations in the PFC display a high negative correlation throughout the different anaesthetic phases. These findings suggest that deoxyHb could be a reliable marker for monitoring anaesthetic depth, and that the PFC intervenes in the suppression and emergence of consciousness.

  11. [The hemoglobin of adult Andean condors (Vultur gryphus, Cathartiformes). The amino acid sequence of the major (HbA) and minor component (HbD)].

    PubMed

    Bauer, H; Braunitzer, G; Oberthür, W; Kösters, J; Grimm, F

    1985-12-01

    The complete amino-acid sequence of the alpha A- and the beta-chains of the major component (HbA) and the alpha D- and the beta-chains of the minor component (HbD) of Andean Condor (Vultur gryphus) is presented. The minor component with the alpha D-chains is present in smaller amounts (17%) than in other birds (25%). The comparison with the corresponding chains of Greylag Goose (Anser anser) shows 17 different amino acids (17 nucleotides, only one-point mutations) in the alpha A-chains and 8 (8 nucleotides) in the beta-chains. The alpha D-chains differ from those of the pheasant (Phasanius cholchicus cholchicus) in 24 amino acids (27 nucl., 3 two-point mutations). Seven alpha 1 beta 1-, one alpha 1 beta 2-, three alpha 1 alpha 1-contacts and one beta 1 beta 1-contact are exchanged. The systematy of Cathartiformes, Ciconiiformes and Phoenicopteriformes is discussed, based on the amino-acid exchanges of all known adult hemoglobins of birds.

  12. Identification, Functional Study, and Promoter Analysis of HbMFT1, a Homolog of MFT from Rubber Tree (Hevea brasiliensis)

    PubMed Central

    Bi, Zhenghong; Li, Xiang; Huang, Huasun; Hua, Yuwei

    2016-01-01

    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. PMID:26950112

  13. High Frequency of Hb E-Saskatoon (HBB: c.67G > A) in Brazilians: A New Genetic Origin?

    PubMed

    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

    2016-08-01

    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.

  14. Transcriptional repression of BODENLOS by HD-ZIP transcription factor HB5 in Arabidopsis thaliana

    PubMed Central

    De Smet, Ive; Lau, Steffen; Ehrismann, Jasmin S.; Axiotis, Ioannis; Kolb, Martina; Kientz, Marika; Weijers, Dolf; Jürgens, Gerd

    2013-01-01

    In Arabidopsis thaliana, the phytohormone auxin is an important patterning agent during embryogenesis and post-embryonic development, exerting effects through transcriptional regulation. The main determinants of the transcriptional auxin response machinery are AUXIN RESPONSE FACTOR (ARF) transcription factors and AUXIN/INDOLE-3-ACETIC ACID (AUX/IAA) inhibitors. Although members of these two protein families are major developmental regulators, the transcriptional regulation of the genes encoding them has not been well explored. For example, apart from auxin-linked regulatory inputs, factors regulating the expression of the AUX/IAA BODENLOS (BDL)/IAA12 are not known. Here, it was shown that the HOMEODOMAIN-LEUCINE ZIPPER (HD-ZIP) transcription factor HOMEOBOX PROTEIN 5 (HB5) negatively regulates BDL expression, which may contribute to the spatial control of BDL expression. As such, HB5 and probably other class I HD-ZIP proteins, appear to modulate BDL-dependent auxin response. PMID:23682118

  15. Involvement of HbPIP2;1 and HbTIP1;1 aquaporins in ethylene stimulation of latex yield through regulation of water exchanges between inner liber and latex cells in Hevea brasiliensis.

    PubMed

    Tungngoen, Kessarin; Kongsawadworakul, Panida; Viboonjun, Unchera; Katsuhara, Maki; Brunel, Nicole; Sakr, Soulaiman; Narangajavana, Jarunya; Chrestin, Hervé

    2009-10-01

    Natural rubber is synthesized in specialized articulated cells (laticifers) located in the inner liber of Hevea brasiliensis. Upon bark tapping, the laticifer cytoplasm (latex) is expelled due to liber tissue turgor pressure. In mature virgin (untapped) trees, short-term kinetic studies confirmed that ethylene, the rubber yield stimulant used worldwide, increased latex yield, with a concomitant decrease in latex total solid content, probably through water influx in the laticifers. As the mature laticifers are devoid of plasmodesmata, the rapid water exchanges with surrounding liber cells probably occur via the aquaporin pathway. Two full-length aquaporin cDNAs (HbPIP2;1 and HbTIP1;1, for plasma membrane intrinsic protein and tonoplast intrinsic protein, respectively) were cloned and characterized. The higher efficiency of HbPIP2;1 than HbTIP1;1 in increasing plasmalemma water conductance was verified in Xenopus laevis oocytes. HbPIP2;1 was insensitive to HgCl(2). In situ hybridization demonstrated that HbPIP2;1 was expressed in all liber tissues in the young stem, including the laticifers. HbPIP2;1 was up-regulated in both liber tissues and laticifers, whereas HbTIP1;1 was down-regulated in liber tissues but up-regulated in laticifers in response to bark Ethrel treatment. Ethylene-induced HbPIP2;1 up-regulation was confirmed by western-blot analysis. The promoter sequences of both genes were cloned and found to harbor, among many others, ethylene-responsive and other chemical-responsive (auxin, copper, and sulfur) elements known to increase latex yield. Increase in latex yield in response to ethylene was emphasized to be linked with water circulation between the laticifers and their surrounding tissues as well as with the probable maintenance of liber tissue turgor, which together favor prolongation of latex flow.

  16. DNA studies are necessary for accurate patient diagnosis in compound heterozygosity for Hb Adana (HBA2:c.179>A) with deletional or nondeletional α-thalassaemia

    PubMed Central

    Tan, Jin Ai Mary Anne; Kho, Siew Leng; Ngim, Chin Fang; Chua, Kek Heng; Goh, Ai Sim; Yeoh, Seoh Leng; George, Elizabeth

    2016-01-01

    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 (-α3.7), 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 (αcodon 59α/αCSα) 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 (αcodon 59α/αPakséα) after nine years of being misdiagnosis with Hb Adana and HbCS (αcodon 59α/αCSα). 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. PMID:27271331

  17. Underpotential Deposition of Cu on Au(111): Implications of the HB model

    DTIC Science & Technology

    1994-05-04

    PROJECT ITASK tWORK UNIT Virginia 22217-5000 ELEMENT NO NO. NO, ACCESSION NO 11. TITLE (include Security Classification) UNDERPOTENTIAL DEPOSITION OF...block number) In recent papers a model for the underpotential deposition of Cu on Au(lll) in the presence of bisulfate ions was proposed. In this model... UNDERPOTENTIAL DEPOSITION OF Cu ON Au(111): IMPLICATIONS OF THE HB MODEL by L. Blum* and Dale A. Huckaby’* Prepared for Publication in The Journal of

  18. The Importance of HbA1c Control in Patients with Subclinical Hypothyroidism

    PubMed Central

    Billic-Komarica, Edina; Beciragic, Amela; Junuzovic, Dzelaludin

    2012-01-01

    Goal: To investigate the correlation between TSH and HbA1c in the treatment of L-thyroxine in the process of glycemic control in patients with subclinical hypothyroidism. Patients and methods: The sample consisted of 100 patients, mean age 51.75±3.23 years, BMI=27.97±4.52 kg/m2, with SH (TSH>4.2 mU/L and normal serum T3 and T4). Laboratory diagnosis included the determination of free T3, free T4, thyroid antibodies, Tg, insulin, C-peptide and glucose during the OGTT, HbA1c, CRP and lipid levels. 20 patients with SH had prediabetes and 38 patients had DM. All patients were treated with low doses of L-thyroxine (25-50ug) and all were physically active. Results: After 6 months of treatment with L-thyroxine, the patients had normal or decreased TSH (5.85±0.92 vs. 3.54±0.55 mU/L), insulin levels (114.64±24.11 vs. 96.44±17.26 pmol/L) significantly reduced HbA1c (6.74±1.01 vs. 6.26±1.12) is reduced. Conclusion: The correlation between TSH and HbA1c was positive and significant (r=0.46). This indicates a significant effect of treatment with L-thyroxine on glycemic control in patients with subclinical hypothyroidism. PMID:23678326

  19. Fermi LAT and WMAP observations of the supernova remnant HB 21

    SciTech Connect

    Pivato, G.; Hewitt, J. W.; Tibaldo, L.; Acero, F.; Brandt, T. J.; Ballet, J.; Janssen, G. H.; Jóhannesson, G.; Smith, D. A. E-mail: john.w.hewitt@nasa.gov

    2013-12-20

    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.

  20. NIR flaring of the Gamma ray source [HB89] 0754+100

    NASA Astrophysics Data System (ADS)

    Carrasco, L.; Mayya, D., Y.; Carramiñana, A.; Recillas, E.; Porras, A.

    2010-03-01

    We call attention on our recent observation of the Gamma Ray source [HB89] 0754+100 with the CANICA NIR camera on the 2.1m telescope at the Observatorio Astrofísico Guillermo Haro, located in Cananea, Mexico. We found this BLLac type object, to show fluxes about 2 magnitudes brighter than our previous observation 30 days earlier. Below, we list our photometric results in the H Band for this period.

  1. A Recent NIR Flare of the QSO HB891803+784

    NASA Astrophysics Data System (ADS)

    Carrasco, L.; Porras, A.; Carraminana, A.; Recillas, E.; Chavushyan, V.; Mayya, D. Y.

    2014-08-01

    We call your attention on our recent observations in the NIR of the Gamma Ray source 2FGLJ1800.5+7829 related with the radio source S5 1803+78 and the quasar HB891803+784 (z=0.68) with the CANICA NIR camera on the 2.1m telescope at the Observatorio Astrofisico Guillermo Haro, located in Cananea, Mexico.

  2. Further study on spectrophotometric determination of CO--Hb in post-mortem blood.

    PubMed

    Hayashi, T; Nanikawa, R

    1978-01-01

    The method for spectrophotometric determination of CO--Hb in blood on the basis of difference in absorbancies of deoxy- and carboxy-hemoglobin reported previously [1] was further improved. The total blood hemoglobin content was determined by the azide-methemoglobin method instead of the well-known cyanmethemoglobin method. This method was found to be useful even if applied to old or putrefied blood samples.

  3. Effects of CRM197, a specific inhibitor of HB-EGF, in oral cancer.

    PubMed

    Dateoka, Suguru; Ohnishi, Yuichi; Kakudo, Kenji

    2012-06-01

    CRM197, a nontoxic mutant of diphtheria toxin, is a specific inhibitor of heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF), which belongs to the EGF family that has been implicated in the increased progression, proliferation, and metastasis of oral cancer. In this study, we analyzed the antitumor effects of CRM197, which represent possible chemotherapeutic agents for oral cancer. In the experiment, we used the oral squamous cell carcinoma cell lines HSC3 and SAS. Cells treated with CRM197 were analyzed based on cell viability, MTT assay, invasion assay, Western blot, and zymography. HSC3 cells were injected subcutaneously into female BALB/c nu/nu mice at 5 weeks of age. CRM197 and/or CDDP were injected intraperitoneally into tumor-bearing mice, and tumor volume was measured over time. HB-EGF expression in HSC3 and SAS cells treated with CRM197 was significantly reduced and cell proliferation was inhibited. The invasiveness of CRM197-treated cells was relatively low. MMP-9 and VEGF were suppressed in HSC3 treated with CRM197 on zymography and Western blot. Further, tumor growth in xenografted mice was suppressed by CRM197 or CDDP at 1 mg/kg/day. Also, the coadministration of CDDP and CRM197 at 1 mg/kg/day completely inhibited tumor formation. These results suggest that HB-EGF is a target for oral cancer and that CRM197 is effective in oral cancer therapy.

  4. Determination of filter pore size for use in HB line phase II production of plutonium oxide

    SciTech Connect

    Shehee, T.; Crowder, M.; Rudisill, T.

    2014-08-01

    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.

  5. Organisation of the Hb 1 genes of the Antarctic skate Bathyraja eatonii: new insights into the evolution of globin genes.

    PubMed

    Marino, Katia; Boschetto, Loredana; de Pascale, Donatella; Cocca, Ennio

    2007-12-30

    An extensive investigation of the organisation of globin genes has greatly contributed to the understanding of universal mechanisms of gene evolution and expression. Cartilaginous fish are the first organisms that have evolved the tetrameric form of hemoglobin (Hb). So far, there has been absolute lack of data about globin genes in chondrichthyans. Bathyraja is the dominant rajid south of 60 degrees S. In the framework of the investigations on globin genes of Antarctic red-blooded and Hb-less fish we obtained the cloning of the alpha- and beta-globin cDNAs of the main Hb (Hb 1) of the skate Bathyraja eatonii. Then, a genomic fragment of 6.2 kb was isolated where the Hb 1 alpha and beta genes are linked in a tail-to-head (3' to 5') orientation. The beta-globin gene promoter region and the chromosomal organisation of the Hb 1 genes of B. eatonii have been compared to their homologues in other vertebrates. The finding of a tail-to-head linkage of the Hb 1 alpha- and beta-globin genes in B. eatonii is the first characterisation of the organisation of globin genes in chondrichthyes; such finding offers a novel contribution to the understanding of the evolution of this class of genes. Moreover, the characterisation of chondrichthyan genes is very important for gaining insight into the ancestral state of vertebrate genomes.

  6. The homeodomain transcription factor Hb9 controls axon guidance in Drosophila through the regulation of Robo receptors.

    PubMed

    Santiago, Celine; Labrador, Juan-Pablo; Bashaw, Greg J

    2014-04-10

    Transcription factors establish neural diversity and wiring specificity; however, how they orchestrate changes in cell morphology remains poorly understood. The Drosophila Roundabout (Robo) receptors regulate connectivity in the CNS, but how their precise expression domains are established is unknown. Here, we show that the homeodomain transcription factor Hb9 acts upstream of Robo2 and Robo3 to regulate axon guidance in the Drosophila embryo. In ventrally projecting motor neurons, hb9 is required for robo2 expression, and restoring Robo2 activity in hb9 mutants rescues motor axon defects. Hb9 requires its conserved repressor domain and functions in parallel with Nkx6 to regulate robo2. Moreover, hb9 can regulate the medio-lateral position of axons through robo2 and robo3, and restoring robo3 expression in hb9 mutants rescues the lateral position defects of a subset of neurons. Altogether, these data identify Robo2 and Robo3 as key effectors of Hb9 in regulating nervous system development.

  7. Association of HbA1c and cardiovascular and renal disease in an adult Mediterranean population

    PubMed Central

    2013-01-01

    Background Increasing evidence suggests a mechanistic link between the glycemic environment and renal and cardiovascular events, even below the threshold for diabetes. We aimed to assess the association between HbA1c and chronic kidney disease (CKD) and cardiovascular disease (CVD). Methods A cross-sectional study involving a random representative sample of 2270 adults from southern Spain (Malaga) was undertaken. We measured HbA1c, serum creatinine and albuminuria in fasting blood and urine samples. Results Individuals without diabetes in the upper HbA1c tertile had an unfavorable cardiovascular and renal profile and shared certain clinical characteristics with the patients with diabetes. Overall, a higher HbA1c concentration was strongly associated with CKD or CVD after adjustment for traditional risk factors. The patients with known diabetes had a 2-fold higher odds of CKD or CVD. However, when both parameters were introduced in the same model, the HbA1c concentration was only significantly associated with clinical endpoints (OR: 1.4, 95% CI, 1.1-1.6, P = 0.002). An increase in HbA1c of one percentage point was associated with a 30% to 40% increase in the rate of CKD or CVD. This relationship was apparent in persons with and without known diabetes. ROC curves illustrated that a HbA1c of 37 mmol/mol (5.5%) was the optimal value in terms of sensitivity and specificity for predicting endpoints in this population. Conclusion HbA1c levels were associated with a higher prevalence of CKD and CVD cross-sectionally, regardless of diabetes status. These data support the value of HbA1c as a marker of cardiovascular and renal disease in the general population. PMID:23865389

  8. HB-EGF release mediates glucose-induced activation of the epidermal growth factor receptor in mesangial cells.

    PubMed

    Uttarwar, L; Peng, F; Wu, D; Kumar, S; Gao, B; Ingram, A J; Krepinsky, J C

    2011-04-01

    Glomerular matrix accumulation is a hallmark of diabetic nephropathy. We showed that transactivation of the epidermal growth factor receptor (EGFR) is an important mediator of matrix upregulation in mesangial cells (MC) in response to high glucose (HG). Here, we study the mechanism of EGFR transactivation. In primary MC, EGFR transactivation by 1 h of HG (30 mM) was unaffected by inhibitors of protein kinase C, reactive oxygen species, or the angiotensin II AT1 receptor. However, general metalloprotease inhibition, as well as specific inhibitors of heparin-binding EGF-like growth factor (HB-EGF), prevented both EGFR and downstream Akt activation. HB-EGF was released into the medium by 30 min of HG, and this depended on metalloprotease activity. One of the metalloproteases shown to cleave proHB-EGF is ADAM17 (TACE). HG, but not an osmotic control, activated ADAM17, and its inhibition prevented EGFR and Akt activation and HB-EGF release into the medium. siRNA to either ADAM17 or HB-EGF prevented HG-induced EGFR transactivation. We previously showed that EGFR/Akt signaling increases transforming growth factor (TGF)-β1 transcription through the transcription factor activator protein (AP)-1. HG-induced AP-1 activation, as assessed by EMSA, was abrogated by inhibitors of metalloproteases, HB-EGF and ADAM17. HB-EGF and ADAM17 siRNA also prevented AP-1 activation. Finally, these inhibitors and siRNA prevented TGF-β1 upregulation by HG. Thus, HG-induced EGFR transactivation in MC is mediated by the release of HB-EGF, which requires activity of the metalloprotease ADAM17. The mechanism of ADAM17 activation awaits identification. Targeting upstream mediators of EGFR transactivation including HB-EGF or ADAM17 provides novel therapeutic targets for the treatment of diabetic nephropathy.

  9. Maternal Hb during pregnancy and offspring's educational achievement: a prospective cohort study over 30 years.

    PubMed

    Fararouei, Mohammad; Robertson, Claire; Whittaker, John; Sovio, Ulla; Ruokonen, Aimo; Pouta, Anneli; Hartikainen, Anna-Liisa; Jarvelin, Marjo-Riitta; Hyppönen, Elina

    2010-11-01

    The aim of the present study was to examine the association between maternal Hb levels during pregnancy and educational achievement of the offspring in later life. We analysed data obtained from the Northern Finnish Birth Cohort Study conducted in 1966, in which, data on mothers and offspring from pregnancy through to the age of 31 years were collected. The cohort comprised 11 656 individuals born from singleton births (51 % males and 49 % females). Maternal Hb levels were available from the third, seventh and ninth gestational months. Educational achievement was measured as school scores (range 4-10) taken at the ages of 14 (self-reported questionnaires) and 16 (school reports) years as well as the highest level of education at the age of 31 years. The present results showed a direct positive association between Hb levels and educational achievement in later life. After adjustment for sex, birth weight, birth month and a wide range of maternal factors (parity, smoking, mental status, whether pregnancy was wanted or not, education, social class and marital status), only maternal Hb levels that were measured at the ninth month were significantly associated with the offspring's school performance. If the levels were ≥ 110 g/l at all the three measurement points, offspring not only had better school scores at the ages of 14 and 16 years (β = 0·048, P = 0·04 and β = 0·68, P = 0·007, respectively), but also had an increased odds of having a higher level of education at the age of 31 years (OR = 1·14, P = 0·04). The present study suggests that low maternal Hb levels at the final stages of pregnancy are linked to the poorer educational achievement of the offspring. If our observation is confirmed, it would suggest that Fe prophylaxis even at fairly late stages of pregnancy may be beneficial for the subsequent health of the offspring. However, more studies are needed to fully establish the potential pathways and the clinical importance of the

  10. Inpatient HbA1c testing: a prospective observational study

    PubMed Central

    Nanayakkara, Natalie; Nguyen, Hang; Churilov, Leonid; Kong, Alvin; Pang, Nyuk; Hart, Graeme K; Owen-Jones, Elizabeth; White, Jennifer; Ross, Jane; Stevenson, Victoria; Bellomo, Rinaldo; Lam, Que; Crinis, Nicholas; Robbins, Raymond; Johnson, Doug; Baker, Scott T; Zajac, Jeffrey D; Ekinci, Elif I

    2015-01-01

    Objective To use admission inpatient glycated hemoglobin (HbA1c) testing to help investigate the prevalence of unrecognized diabetes, the cumulative prevalence of unrecognized and known diabetes, and the prevalence of poor glycemic control in both. Moreover, we aimed to determine the 6-month outcomes for these patients. Finally, we aimed to assess the independent association of diabetes with these outcomes. Research, design, and methods Prospective observational cohort study conducted in a tertiary hospital in Melbourne, Australia. Patients A cohort of 5082 inpatients ≥54 years admitted between July 2013 and January 2014 underwent HbA1c measurement. A previous diagnosis of diabetes was obtained from the hospital medical record. Patient follow-up was extended to 6 months. Results The prevalence of diabetes (known and unrecognized) was 34%. In particular, we identified that unrecognized but HbA1c-confirmed diabetes in 271 (5%, 95% CI 4.7% to 6.0%) patients, previously known diabetes in 1452 (29%, 95% CI 27.3% to 29.8%) patients; no diabetes in 3359 (66%, 95% CI 64.8–67.4%) patients. Overall 17% (95% CI 15.3% to 18.9%) of patients with an HbA1c of >6.5% had an HbA1c ≥8.5%. After adjusting for age, gender, Charlson Index score, estimated glomerular filtration rate, and hemoglobin levels, with admission unit treated as a random effect, patients with previously known diabetes had lower 6-month mortality (OR 0.69, 95% CI 0.56 to 0.87, p=0.001). However, there were no significant differences in proportions of intensive care unit admission, mechanical ventilation or readmission within 6 months between the 3 groups. Conclusions Approximately one-third of all inpatients ≥54 years of age admitted to hospital have diabetes of which about 1 in 6 was previously unrecognized. Moreover, poor glycemic control was common. Proportions of intensive care unit admission, mechanical ventilation, or readmission were similar between the groups. Finally, diabetes was

  11. Diabetes mellitus: the long way of standardization of HbA(1c) to the level of highest metrological order.

    PubMed

    Kaiser, Patricia; Reinauer, Hans

    2011-01-01

    Glycated haemoglobin (HbA(1c)) measurements are used in clinical studies and for the management of diabetic patients. Various efforts were made to standardize the HbA(1c) 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 HbA(1c) this has been realized using a LC-ID-MS procedure based on the existing reference measurement procedure.

  12. A new alpha chain hemoglobin variant: Hb Al-Hammadi Riyadh [alpha75(EF4)Asp-->Val (alpha2)].

    PubMed

    Burnichon, Nelly; Lacan, Philippe; Becchi, Michel; Zanella-Cleon, Isabelle; Aubry, Martine; Mowafy, Mohammed; Couprie, Nicole; Francina, Alain

    2006-01-01

    A new hemoglobin (Hb) variant in the heterozygous state, Hb Al-Hammadi Riyadh [codon 75 (GAC-->GTC); alpha75(EF4)Asp-->Val (alpha2)] corresponding to an A-->T transversion on the second exon of the alpha2-globin gene, is described. The variant was characterized by DNA sequencing and mass spectrometry (MS). The variant was found during a routine Hb analysis for anemia in a 16-month-old boy who lived in Riyadh, Kingdom of Saudi Arabia.

  13. Capsicum annuum homeobox 1 (CaHB1) is a nuclear factor that has roles in plant development, salt tolerance, and pathogen defense

    SciTech Connect

    Oh, Sang-Keun; Yoon, Joonseon; Choi, Gyung Ja; Jang, Hyun A; Kwon, Suk-Yoon; Choi, Doil

    2013-12-06

    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.

  14. 77 FR 5566 - Notice of Availability of the Final EIS for the HB In-Situ Solution Mine Project, Eddy County...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-03

    ... Bureau of Land Management Notice of Availability of the Final EIS for the HB In-Situ Solution Mine... prepared a Final Environmental Impact Statement (Final EIS) for the HB In-Situ Solution Mine Project, and... Notice of Availability of the Final EIS in the Federal Register. ADDRESSES: Copies of the HB...

  15. A study assessing the association of glycated hemoglobin A1C (HbA1C) associated variants with HbA1C, chronic kidney disease and diabetic retinopathy in populations of Asian ancestry.

    PubMed

    Chen, Peng; Ong, Rick Twee-Hee; Tay, Wan-Ting; Sim, Xueling; Ali, Mohammad; Xu, Haiyan; Suo, Chen; Liu, Jianjun; Chia, Kee-Seng; Vithana, Eranga; Young, Terri L; Aung, Tin; Lim, Wei-Yen; Khor, Chiea-Chuen; Cheng, Ching-Yu; Wong, Tien-Yin; Teo, Yik-Ying; Tai, E-Shyong

    2013-01-01

    Glycated hemoglobin A1C (HbA1C) level is used as a diagnostic marker for diabetes mellitus and a predictor of diabetes associated complications. Genome-wide association studies have identified genetic variants associated with HbA1C level. Most of these studies have been conducted in populations of European ancestry. Here we report the findings from a meta-analysis of genome-wide association studies of HbA1C levels in 6,682 non-diabetic subjects of Chinese, Malay and South Asian ancestries. We also sought to examine the associations between HbA1C associated SNPs and microvascular complications associated with diabetes mellitus, namely chronic kidney disease and retinopathy. A cluster of 6 SNPs on chromosome 17 showed an association with HbA1C which achieved genome-wide significance in the Malays but not in Chinese and Asian Indians. No other variants achieved genome-wide significance in the individual studies or in the meta-analysis. When we investigated the reproducibility of the findings that emerged from the European studies, six loci out of fifteen were found to be associated with HbA1C with effect sizes similar to those reported in the populations of European ancestry and P-value ≤ 0.05. No convincing associations with chronic kidney disease and retinopathy were identified in this study.

  16. Immune safety evaluation of polymerized porcine hemoglobin (pPolyHb): a potential red blood cell substitute.

    PubMed

    Zhu, Hongli; Yan, Kunping; Dang, Xiaodong; Huang, He; Chen, Erfang; Chen, Bang; Luo, Chao; Chang, Thomas Ming Swi; Dai, Penggao; Chen, Chao

    2011-12-01

    Polymerized Porcine Hemoglobin (pPolyHb), a hemoglobin-based oxygen carrier (HBOC), was developed as a potential red blood substitute for clinical applications. Assessment of its effects on the immune system is an important component of the overall safety evaluation of HBOC. For this purpose, we assessed three inflammation indicators, including complement C3a, IL-6, and TNF-? in cultured cells and in a rat model when pPolyHb was incubated or administrated with the cells/animals. Our results suggested that the levels of these three indicators were not statistically changed upon pPolyHb stimulation, indicating that pPolyHb is not immunotoxic to cells and animals in this aspect.

  17. Implications of iron deficiency/anemia on the classification of diabetes using HbA1c

    PubMed Central

    Attard, S M; Herring, A H; Wang, H; Howard, A-G; Thompson, A L; Adair, L S; Mayer-Davis, E J; Gordon-Larsen, P

    2015-01-01

    Background/Objectives: 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. Subjects/Methods: 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. Results: 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. Conclusions: 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

  18. Source Terms for HFIR Beam Tube Shielding Analyses, and a Complete Shielding Analysis of the HB-3 Tube

    SciTech Connect

    Bucholz, J.A.

    2000-07-01

    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.

  19. A new G(gamma) chain variant: Hb F-Bron [gamma20(B2)val-->Ala].

    PubMed

    Lacan, Philippe; Burnichon, Nelly; Becchi, Michel; Zanella-Cleon, Isabelle; Aubry, Martine; Couprie, Nicole; Francina, Alain

    2005-01-01

    A new G(gamma) hemoglobin (Hb) variant, Hb F-Bron [gamma20(B2)Val-->Ala] on the first exon of the G(gamma)-globin gene is described. The variant was characterized by DNA sequencing and mass spectrometry (MS). Hematological abnormalities included hypochromia and microcytosis and were probably caused by an interaction with an alpha-thalassemia (thal) (3.7 kb) deletion in the heterozygous state.

  20. Measurement of HbA1c from stored whole blood samples in the Atherosclerosis Risk in Communities study

    PubMed Central

    SELVIN, Elizabeth; CORESH, Josef; ZHU, Hong; FOLSOM, Aaron; STEFFES, Michael W.

    2010-01-01

    Background The aims of the present study were to demonstrate the reliability of HbA1c measurements across two time periods and to compare these measurements with HbA1c distribution in the general US population. Methods HbA1c was measured in 14 069 whole blood samples in the Atherosclerosis Risk in Communities (ARIC) study using different HPLC instruments during two time periods, namely 2003–2004 and 2007–2008. At the time of measurement, samples had been in storage at –70°C for 14–18 years. To assess differences in values, HbA1c measurements were repeated in 383 samples at both periods. Indirect comparisons were made by comparing our measurements against those from a nationally representative study. Results The coefficients of variation for quality control samples were 1.8% (n = 89) in 2003–2004 and 1.4% (n = 259) in 2007–2008. The correlation between measurements at the two time points was high (r = 0.99), but with a slight bias: 0.29% points higher in 2007–2008 versus 2003–2004 (n = 383; P < 0.0001). The comparison yielded the following Deming regression equation: y(2007–2008) = 0.073+1.034x(2003–2004). After alignment using this equation, the distribution of HbA1c in the ARIC study was similar to that in the national study using fresh samples. Conclusions Measurements of HbA1c from samples stored for 14–18 years are highly reliable when using state-of-the-art HPLC instruments, but with some bias introduced over time. The HbA1c data now available in the ARIC study should be invaluable for investigations into the clinical utility of HbA1c as a diagnostic test for diabetes. PMID:20923494

  1. HbA1c for the diagnosis of diabetes mellitus in a developing country. A position article.

    PubMed

    Gomez-Perez, Francisco J; Aguilar-Salinas, Carlos A; Almeda-Valdes, Paloma; Cuevas-Ramos, Daniel; Lerman Garber, Israel; Rull, Juan A

    2010-05-01

    An Expert Committee of the American Diabetes Association and the European Association for the Study of Diabetes recommended a move to the use of HbA1c level to diagnose diabetes mellitus. Diagnosis should be made if the A1c level is > or = 6.5%. HbA1c provides a reliable measure of chronic glycemia, correlates well with the risk of long-term diabetes complications and technical limitations for standardization have been overcome in laboratories of the U.S. and Europe. The objective of this paper is to analyze critically the advantages and disadvantages of the use of HbA1c as a diagnostic method of diabetes in a developing country. The lack of a universal threshold for the diagnosis of diabetes, the cost of the test and the absence of the standardization network in the majority of the countries are major arguments for not including HbA1c as diagnostic criteria of diabetes. HbA1c diagnostic criteria has a low sensitivity. As a result, there is a lack of agreement between the HbA1c criteria with the other diagnostic methods that lead into significant variations in the number of affected cases. In addition, sensitivity and specificity vary among ethnic groups. No study has compared the diagnostic properties of the HbA1c in Latin America. In conclusion, the logistic limitations that exist in a large proportion of developing countries and the unsolved uncertainties that exist for the definition of the A1c criterion are strong arguments against the inclusion of HbA1c among the diagnostic criteria of diabetes.

  2. Identification of Hb Constant Spring (HBA2: c.427T > C) by an Automated High Performance Liquid Chromatography Method.

    PubMed

    Wisedpanichkij, Raewadee; Jindadamrongwech, Sumalee; Butthep, Punnee

    2015-01-01

    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.

  3. Association between HbA1c and carotid atherosclerosis among elderly Koreans with normal fasting glucose

    PubMed Central

    Lee, Seung Won; Kim, Hyeon Chang; Lee, Yong-ho; Song, Bo Mi; Choi, Hansol; Park, Ji Hye; Rhee, Yumie; Kim, Chang Oh

    2017-01-01

    Aim We examined whether glycated haemoglobin (HbA1c) is associated to carotid atherosclerosis in an elderly Korean population with normal fasting glucose. Methods 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. Results 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. Conclusion 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. PMID:28178313

  4. HbMyb1, a Myb transcription factor from Hevea brasiliensis, suppresses stress induced cell death in transgenic tobacco.

    PubMed

    Peng, Shi-Qing; Wu, Kun-Xin; Huang, Gui-Xiu; Chen, Shou-Cai

    2011-12-01

    Tapping panel dryness (TPD) is a complex physiological syndrome found widely in rubber tree (Hevea brasiliensis) plantations that causes severe yield loss in natural rubber-producing countries. In an earlier study, we confirmed that there is a negative correlation between HbMyb1 expression and TPD severity. To further investigate the function of HbMyb1 in TPD, HbMyb1 was over-expressed in tobacco controlled by a CaMV 35S promoter. In transgenic plants expressing HbMyb1, cell death induced by UV-B irradiation, paraquat and the hypersensitive reaction to necrotrophic fungal infection (Botrytis cinerea) was suppressed with a close correlation between HbMyb1 protein levels and the extent of suppression. In addition the nuclear condensation and degradation were observed in laticifer cells of TPD trees, while the nucleus of laticifer cells of healthy trees was morphologically normal. On the basis of the results described above, we propose that HbMyb1 maybe suppress stress induced cell death in rubber trees.

  5. Effect of the systemic inflammatory response, as provoked by elective orthopaedic surgery, on HbA1c.

    PubMed

    Chadburn, Andrew J; Garman, Elizabeth; Abbas, Raad; Modupe, Anu; Ford, Clare; Thomas, Osmond L; Chugh, Sanjiv; Deshpande, Shreeram; Gama, Rousseau

    2017-01-01

    Background In acutely ill patients with new onset hyperglycaemia, plasma glucose cannot reliably distinguish between stress hyperglycaemia and undiagnosed diabetes mellitus. We, therefore, investigated the diagnostic reliability of glycated haemoglobin (HbA1c) in acute illness by prospectively evaluating the effect of the systemic inflammatory response, as provoked by elective orthopaedic surgery, on HbA1c. Methods HbA1c and serum C-reactive protein concentrations were compared before and two days after elective knee or hip surgery in 30 patients without diabetes. C-reactive protein was used to assess the systemic inflammatory response. Results The mean (standard deviation) serum C-reactive protein increased following surgery (4.8 [7.5] vs. 179.7 [61.9] mg/L; P<0.0001). HbA1c was similar before and after surgery (39.2 [5.4] vs. 38.1 [5.1] mmol/moL, respectively; P = 0.4363). Conclusions HbA1c is unaffected within two days of a systemic inflammatory response as provoked by elective orthopaedic surgery. This suggests that HbA1c may be able to differentiate newly presenting type 2 diabetes mellitus from stress hyperglycaemia in acutely ill patients with new onset hyperglycaemia.

  6. Interaction between the Supernova Remnant HB 3 and the Nearby Star-forming Region W3

    NASA Astrophysics Data System (ADS)

    Zhou, Xin; Yang, Ji; Fang, Min; Su, Yang; Sun, Yan; Chen, Yang

    2016-12-01

    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.

  7. Two new hemoglobin variants: Hb Aix-Les-Bains [β5(A2)Pro→Leu; HBB:c.17 C>T] and Hb Dubai [α122(H5)His→Leu (α2); HBA2:c.368 A>T].

    PubMed

    Joly, Philippe; Garcia, Caroline; Lacan, Philippe; Couprie, Nicole; Francina, Alain

    2011-01-01

    We report two new hemoglobin (Hb) variants; one causing an impairment of the N-terminal glycation of the β-globin chain and the other a hematological phenotype of α-thalassemia (α-thal). The first variant is Hb Aix-les-Bains [β5(A2)Pro→Leu] and the second Hb Dubai [α122(H5)His→Leu (α2)]. These two new Hb variants were detected by chromatographic and electrophoretic methods and characterized by molecular studies. Hb Dubai gives an α-thalassemic phenotype and should be routinely detected for preventing severe Hb H disease in couples at-risk for α-thal.

  8. Boussinesq modeling of HB06 tracer releases Part 2: Tracer plumes

    NASA Astrophysics Data System (ADS)

    Clark, D. B.; Feddersen, F.; Guza, R. T.

    2010-12-01

    Tracer plumes simulated with a Boussinesq surfzone model (funwaveC) are compared with 5 plumes observed during the HB06 experiment (Huntington Beach, Fall 2006). Surfzone tracer plumes were formed by continuously releasing dye tracer into the wave-driven alongshore current. Bulk cross-shore eddy diffusivities, O(1 m2 s-1), were estimated from the observed plumes and agreed best with a mixing-length scaling based on large 2D eddies [Clark et al., JGR, in press 2010]. The mechanisms for surfzone cross-shore tracer dispersion are not well known, and are explored here with the time-dependent, wave and horizontal eddy resolving, funwaveC model. The funwaveC model is run with observed bathymetry, and initialized in 4m depth with the observed obliquely incident and directionally spread waves. Modeled and observed waves and currents are similar, and discussed in Part 1. Model tracer is dispersed by the surfzone horizontal eddy field, a breaking wave eddy diffusivity, and a small O(0.01 m2 s-1) background diffusivity. Modeled and observed mean plume structures agree, but can be degraded by a mismatch between observed and modeled alongshore currents, especially near the tracer source. Bulk tracer eddy diffusivities agree with HB06 observations, and the long narrow plume assumption (used for diffusion analysis) is discussed with modeled tracer fluxes. The model suggests that cross-shore mixing at time scales of many wave periods is dominated by horizontal eddies, not by the breaking eddy diffusivity.

  9. Features of the electronic structure of the active center of an HbS molecule

    NASA Astrophysics Data System (ADS)

    Novoselov, D. Yu.; Korotin, Dm. M.; Anisimov, V. I.

    2016-01-01

    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.

  10. Xanthochromia of the skull bone associated with HbA1c.

    PubMed

    Schäfer, T; Klintschar, M; Lichtinghagen, R; Plagemann, I; Smith, A; Budde, E; Hagemeier, L

    2016-03-01

    The color of the surface of 105 skull bones (part of the parietal bone) was determined using a portable spectral colorimeter (spectro color(®)). By this means it was possible to characterize the color objectively according to the L*a*b* color system defined by the "International Commission de l'Eclairage" (CIE). Biochemical markers of carbohydrate metabolism, HbA1c from venous blood, and glucose/lactate concentrations from vitreous humor, were also determined, for assessment of the ante-mortem plasma glucose concentration using Traub's sum formula. As biochemical markers for lipid metabolism disorder, cholesterol, triglycerides, high density lipoprotein (HDL), low density lipoprotein (LDL) and very low density lipoprotein (VLDL) were all determined from venous blood. There is a significant correlation of bone yellowing with HbA1c (p<0.001) and age (p<0.001). The literature asserts a significant correlation between diabetic condition and yellowing of the skull bone. Despite efforts to find the substance responsible for the yellowing of the bone in chronic metabolism disorder, no significant correlation was found between bone color and lipoproteins/bone extracted lipid acids.

  11. Role of curcuminoids in ameliorating oxidative modification in β-thalassemia/Hb E plasma proteome.

    PubMed

    Weeraphan, Churat; Srisomsap, Chantragan; Chokchaichamnankit, Daranee; Subhasitanont, Pantipa; Hatairaktham, Suneerat; Charoensakdi, Ratiya; Panichkul, Narumol; Siritanaratkul, Noppadol; Fucharoen, Suthat; Svasti, Jisnuson; Kalpravidh, Ruchaneekorn W

    2013-03-01

    Thalassemic patients often exhibit high levels of oxidative stress and iron overload, which can lead to hazardous complications. Curcuminoids, extracted from the spice turmeric, are known to have antioxidant and iron-chelating properties and have been proposed as a potential upstream therapy of thalassemia. Here we have applied proteomic techniques to study the protein profile and oxidative damage in the plasma of β-thalassemia/Hb E patients before and after treatment with curcuminoids. In this study, 10 β-thalassemia/Hb E patients were treated with 500 mg curcuminoids daily for 12 months. The plasma protein profile and protein carbonyl content were determined at baseline, 6 and 12 months using two-dimensional fluorescence difference gel electrophoresis and carbonyl immunoblotting, respectively. Other hematological, clinical, and biochemical parameters were also analyzed. Twenty-six spots, identified as coagulation factors and proteins involved in iron homeostasis, showed significantly decreased intensity in thalassemic plasma, compared to those of normal subjects. Treatment with curcuminoids up-regulated the plasma levels of these proteins and reduced their oxidative damage. Serum non-transferrin bound iron, platelet factor-3 like activity, oxidative stress parameters and antioxidant enzymes were also improved after curcuminoids treatment. This study is the first proteomic study of plasma in the thalassemic state and also shows the ameliorating role of curcuminoids towards oxidative stress and iron overload in the plasma proteome.

  12. Femtosecond dynamics of decoupled superlattice zones in 4Hb-TaSe2 single crystals

    NASA Astrophysics Data System (ADS)

    Olaoye, O.; Erasmus, N.; Haupt, K.; Schwoerer, H.

    2016-03-01

    Strongly correlated electronic crystal systems marked by temperature-dependent phase transitions often feature an emergence of new structural periodicities, arising from an interplay between modulated electron density and periodic lattice distortion. We investigate the structural evolution of \\sqrt{13}a× \\sqrt{13}a× c superlattice clusters in 4Hb-TaSe2 single crystals on a subpicosecond and atomic resolution via femtosecond electron diffraction (FED). The superlattice clusters comprise of two six-member rings each, related by a rotational symmetry and held in position by Coulombic mode repulsion. The two six-member rings are decoupled into two possible zones, which are further decoupled into respective site-specific satellite reflections in the reciprocal space. Governed by the interlayer interactions and the electron diffraction simulation analysis, FED measurements are used to demonstrate the suppression and dynamics of the decoupled superlattice zones. The simultaneous temporal evolution of the two CDW reflection orders are assigned to the decoupled Raman-active A g and {E}2g soft phonon modes previously reported on an isomorphic crystal structure (4Hb-TaS2). It is found that the charge density wave amplitude mode dominates over the corresponding phase mode.

  13. HbA1c and Glycated Albumin Levels Are High in Gastrectomized Subjects with Iron-Deficiency Anemia.

    PubMed

    Inada, Shinya; Koga, Masafumi

    2017-01-01

    We report that glycated albumin (GA) is higher relative to HbA1c in non-diabetic, gastrectomized subjects without anemia, and thus is a sign of oxyhyperglycemia. It is known that gastrectomized subjects are prone to iron-deficiency anemia (IDA), and that the HbA1c levels of subjects with IDA are falsely high. In the present study, the HbA1c and GA levels of gastrectomized subjects with IDA were compared with gastrectomized subjects without anemia. Seven non-diabetic gastrectomized subjects with IDA were enrolled in the present study. Twenty-eight non-diabetic gastrectomized subjects without anemia matched with the subjects with IDA in terms of age, gender, and body mass index were used as the controls. Although there were no significant differences in fasting plasma glucose and OGTT 2-hour plasma glucose (2-h PG) between the two groups, the HbA1c and GA levels in gastrectomized subjects with IDA were significantly higher than the controls. For all of the gastrectomized subjects (n=35), ferritin exhibited a significant negative correlation with HbA1c and GA, and a significant positive correlation with 2-h PG. In addition, the HbA1c and GA levels exhibited a significant negative correlation with the mean corpuscular hemoglobin and hemoglobin. The HbA1c and GA levels in gastrectomized subjects with IDA were significantly higher than those in controls. The high GA levels are attributed to a tendency in which patients with total gastrectomy, who are prone to IDA, are susceptible to postprandial hyperglycemia and reactive hypoglycemia, which in turn leads to large fluctuations in plasma glucose.

  14. MdHB1 down-regulation activates anthocyanin biosynthesis in the white-fleshed apple cultivar 'Granny Smith'.

    PubMed

    Jiang, Yonghua; Liu, Cuihua; Yan, Dan; Wen, Xiaohong; Liu, Yanli; Wang, Haojie; Dai, Jieyu; Zhang, Yujie; Liu, Yanfei; Zhou, Bin; Ren, Xiaolin

    2017-03-06

    Coloration in apple (Malus×domestica) flesh is mainly caused by the accumulation of anthocyanin. Anthocyanin is biosynthesized through the flavonoid pathway and regulated by MYB, bHLH, and WD40 transcription factors (TFs). Here, we report that the HD-Zip I TF MdHB1 was also involved in the regulation of anthocyanin accumulation. MdHB1 silencing caused the accumulation of anthocyanin in 'Granny Smith' flesh, whereas its overexpression reduced the flesh content of anthocyanin in 'Ballerina' (red-fleshed apple). Moreover, flowers of transgenic tobacco (Nicotiana tabacum 'NC89') overexpressing MdHB1 showed a remarkable reduction in pigmentation. Transient promoter activation assays and yeast one-hybrid results indicated that MdHB1 indirectly inhibited expression of the anthocyanin biosynthetic genes encoding dihydroflavonol-4-reductase (DFR) and UDP-glucose:flavonoid 3-O-glycosyltransferase (UFGT). Yeast two-hybrid and bimolecular fluorescence complementation determined that MdHB1 acted as a homodimer and could interact with MYB, bHLH, and WD40 in the cytoplasm, consistent with its cytoplasmic localization by green fluorescent protein fluorescence observations. Together, these results suggest that MdHB1 constrains MdMYB10, MdbHLH3, and MdTTG1 to the cytoplasm, and then represses the transcription of MdDFR and MdUFGT indirectly. When MdHB1 is silenced, these TFs are released to activate the expression of MdDFR and MdUFGT and also anthocyanin biosynthesis, resulting in red flesh in 'Granny Smith'.

  15. PET studies with low and high affinity dopamine D2 receptor radioligands: Effects of 4-hydroxybutyrate (4HB)

    SciTech Connect

    Gatley, S.J.; Fowler, J.S.; Dewey, S.

    1994-05-01

    D2 radioligands of varying affinities have been developed as PET and SPECT radiotracers, but no consensus has been reached on the abilities of these tracers to quantify D2 receptor concentrations in vivo. Amongst other differences, competition of the radioligand with endogenous DA is expected to depend on affinity for the D2 receptor, so that changes in DA might confound estimates of Bmax. We examined the uptake and kinetics if C-11 raclopride (RAC; Kd = 1.2 nM) and C-11 N-methylspiperone (NMS); Kd = 75 pM in baboon striatum after pretreatment with 4HB (200 mg/Kg, i/v) which inhibits DA release by nigrostriatal nerve terminals. While 4HB diminished uptake (%ID/g) of NMS, it prolonged tissue retention of RAC, confirming previous observations in rodent models. Logan (for RAC) and Patlak (for NMS) plots gave changes of +24% and -20%, respectively, between control and 4HB treated animals. Since decreased competition with DA should increase uptake of NMS as well as RAC the paradoxical decrease in NMS uptake could be due to a second synaptic effect of DA, such as a decrease in agonist mediated internalization of NMS. Alternatively, it could result from an independent effect of 4HB, perhaps related to this drug`s ability to induce anesthesia and to depress cerebral glucose utilization. Although previous work in the rat suggests that 4HB does not alter brain blood flow, we found O-15 water that baboon striatal blood flow was decreased 22% and 42% at 30 and 60 minutes, respectively, after 4HB. Smaller changes were seen in cerebellar blood flow. Though a 4HB induced decrease in blood flow does not rule out a DA mediated alteration in D2 receptor Bmax or Kd for NMS, or other factor, it is unnecessary to invoke this to account for our results.

  16. RhHB1 mediates the antagonism of gibberellins to ABA and ethylene during rose (Rosa hybrida) petal senescence.

    PubMed

    Lü, Peitao; Zhang, Changqing; Liu, Jitao; Liu, Xiaowei; Jiang, Guimei; Jiang, Xinqiang; Khan, Muhammad Ali; Wang, Liangsheng; Hong, Bo; Gao, Junping

    2014-05-01

    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.

  17. CNTO 530 increases expression of HbA and HbF in murine models of β-thalassemia and sickle cell anemia.

    PubMed

    Makropoulos, Dorie A; Achuthanandam, Ram; Avery, Justin; Wilson, Krista; Brosnan, Kerry; Miller, Andrew; Nesspor, Thomas; Chroscinski, Denise; Walker, Mindi; Egenolf, Devon; Huang, ChiChi; Bugelski, Peter J

    2013-01-01

    CNTO 530 is an erythropoietin receptor agonist MIMETIBODYTM construct. CNTO 530 has been shown to be active in a number of rodent models of acquired anemia (e.g. renal insufficiency and chemotherapy induced anemia). We investigated the efficacy of CNTO 530 in murine models of β-thalassemia and sickle cell anemia (Berkeley mice). β- thalassemic mice are deficient in expression of α-globin chain and heterozygous mice are characterized by a clinical syndrome similar to the human β-thalassemia intermedia. Berkeley mice are knocked out for murine alpha and beta globin and are transgenic for human alpha, beta (sickle) and gamma globin genes. Berkeley mice thus express human sickle hemoglobin A (HbS) and can also express human fetal hemoglobin. These mice express a severe compensated hypochromic microcytic anemia and display the sickle cell phenotype. To test the effectiveness of CNTO 530, mice from both genotypes received a single subcutaneous (s.c.) dose of CNTO 530 or darbepoetin-α (as a comparator) at 10,000 U/kg, a dose shown to cause a similar increase in reticulocytes and hemoglobin in normal mice. Hematologic parameters were evaluated over time. CNTO 530, but not darbepoetin-α, increased reticulocytes, red blood cells and total hemoglobin in β- thalassemic mice. In Berkeley mice CNTO 530 showed an increase in reticulocytes, red blood cells, F-cells, total hemoglobin and fetal hemoglobin. In conclusion, CNTO 530 is effective in murine models of β-thalassemia and sickle cell anemia. These data suggest that CNTO 530 may have beneficial effects in patients with genetically mediated hemoglobinopathies.

  18. Comparison of the Current Diagnostic Criterion of HbA1c with Fasting and 2-Hour Plasma Glucose Concentration

    PubMed Central

    Karnchanasorn, Rudruidee; Huang, Jean; Feng, Wei; Chuang, Lee-Ming

    2016-01-01

    To determine the effectiveness of hemoglobin A1c (HbA1c) ≥ 6.5% in diagnosing diabetes compared to fasting plasma glucose (FPG) ≥ 126 mg/dL and 2-hour plasma glucose (2hPG) ≥ 200 mg/dL in a previously undiagnosed diabetic cohort, we included 5,764 adult subjects without established diabetes for whom HbA1c, FPG, 2hPG, and BMI measurements were collected. Compared to the FPG criterion, the sensitivity of HbA1c ≥ 6.5% was only 43.3% (106 subjects). Compared to the 2hPG criterion, the sensitivity of HbA1c ≥ 6.5% was only 28.1% (110 subjects). Patients who were diabetic using 2hPG criterion but had HbA1c < 6.5% were more likely to be older (64 ± 15 versus 60 ± 15 years old, P = 0.01, mean ± STD), female (53.2% versus 38.2%, P = 0.008), leaner (29.7 ± 6.1 versus 33.0 ± 6.6 kg/m2, P = 0.000005), and less likely to be current smokers (18.1% versus 29.1%, P = 0.02) as compared to those with HbA1c ≥ 6.5%. The diagnostic agreement in the clinical setting revealed the current HbA1c ≥ 6.5% is less likely to detect diabetes than those defined by FPG and 2hPG. HbA1c ≥ 6.5% detects less than 50% of diabetic patients defined by FPG and less than 30% of diabetic patients defined by 2hPG. When the diagnosis of diabetes is in doubt by HbA1c, FPG and/or 2hPG should be obtained. PMID:27597979

  19. Glossoscolex paulistus extracellular hemoglobin (HbGp) oligomeric dissociation upon interaction with sodium dodecyl sulfate: Isothermal titration calorimetry (ITC).

    PubMed

    Alves, Fernanda Rosa; Carvalho, Francisco Adriano O; Carvalho, José Wilson P; Tabak, Marcel

    2014-10-01

    Annelid erythrocruorins are respiratory proteins with high cooperativity and low autoxidation rates. The giant extracellular hemoglobin of the earthworm, Glossoscolex paulistus (HbGp), has a molecular mass of 3.6 MDa. In this work, isothermal titration calorimetry (ITC), together with DLS and fluorescence emission have been used to investigate the interaction of SDS with the HbGp in the oxy-form, at pH 7.0. Our ITC and DLS results show that addition of SDS induces oxy-HbGp oligomeric dissociation, while a small amount of protein aggregation is observed only by DLS. Moreover, the oligomeric dissociation process is favored at lower protein concentrations. The temperature effect does not influence significantly the interaction of SDS with the hemoglobin, due to the similarities presented by the critical aggregation concentration (cac) and critical micelle concentration (cmc') for the mixtures. The increase of oxy-HbGp concentration leads to a slight variation of the cac values for the SDS-oxy-HbGp mixture, attributed mainly to the noncooperative electrostatic binding of surfactant to protein. However, the cmc' values increase considerably, associated to a more cooperative hydrophobic binding. Complementary pyrene fluorescence emission studies show formation of pre-micellar structures of the mixture already at lower SDS concentrations. This study opens the possibility of the evaluation of the surfactant effect on the hemoglobin stability by ITC, which is made for the first time with this extracellular hemoglobin.

  20. The sunflower transcription factor HaHB11 improves yield, biomass and tolerance to flooding in transgenic Arabidopsis plants.

    PubMed

    Cabello, Julieta V; Giacomelli, Jorge I; Piattoni, Claudia V; Iglesias, Alberto A; Chan, Raquel L

    2016-03-20

    HaHB11 is a member of the sunflower homeodomain-leucine zipper I subfamily of transcription factors. The analysis of a sunflower microarray hybridized with RNA from HaHB11-transformed leaf-disks indicated the regulation of many genes encoding enzymes from glycolisis and fermentative pathways. A 1300bp promoter sequence, fused to the GUS reporter gene, was used to transform Arabidopsis plants showing an induction of expression after flooding treatments, concurrently with HaHB11 regulation by submergence in sunflower. Arabidopsis transgenic plants expressing HaHB11 under the control of the CaMV 35S promoter and its own promoter were obtained and these plants exhibited significant increases in rosette and stem biomass. All the lines produced more seeds than controls and particularly, those of high expression level doubled seeds yield. Transgenic plants also showed tolerance to flooding stress, both to submergence and waterlogging. Carbohydrates contents were higher in the transgenics compared to wild type and decreased less after submergence treatments. Finally, transcript levels of selected genes involved in glycolisis and fermentative pathways as well as the corresponding enzymatic activities were assessed both, in sunflower and transgenic Arabidopsis plants, before and after submergence. Altogether, the present work leads us to propose HaHB11 as a biotechnological tool to improve crops yield, biomass and flooding tolerance.

  1. Increased oxidative metabolism is associated with erythroid precursor expansion in β0-thalassaemia/Hb E disease.

    PubMed

    Leecharoenkiat, Amporn; Wannatung, Tirawat; Lithanatudom, Pathrapol; Svasti, Saovaros; Fucharoen, Suthat; Chokchaichamnankit, Daranee; Srisomsap, Chantragan; Smith, Duncan R

    2011-10-15

    Erythropoiesis in β0-thalassaemia/Hb E patients, the most common variant form of β-thalassaemia in Southeast Asia, is characterized by accelerated differentiation and over-expansion of erythroid precursor cells. The mechanism driving this accelerated expansion and differentiation remain unknown. To address this issue a proteomic analysis was undertaken to firstly identify proteins differentially expressed during erythroblast differentiation and a second analysis was undertaken to identify proteins differentially expressed between β0-thalassaemia/Hb E erythroblasts and control erythroblasts. The majority of proteins identified as being differentially expressed between β0-thalassaemia/Hb E and control erythroblasts were constituents of the glycolysis/TCA pathway and levels of oxidative stress correlated with the degree of erythroid expansion. A model was constructed linking these observations with previous studies showing increased phosphorylation of ERK1/2 in thalassemic erythroblasts which predicted the increased activation of PKA, PKB and PKC which Western analysis confirmed. Inhibition of PKA or PKC reduced β0-thalassaemia/Hb E erythroblast differentiation and/or expansion. We propose that increased expansion and differentiation of β0-thalassaemia/Hb E erythroblasts occur as a result of feedback loops acting through increased oxidative metabolism.

  2. HB-EGF inhibition in combination with various anticancer agents enhances its antitumor effects in gastric cancer.

    PubMed

    Sanui, Ayako; Yotsumoto, Fusanori; Tsujioka, Hiroshi; Fukami, Tatsuya; Horiuchi, Shinji; Shirota, Kyoko; Yoshizato, Toshiyuki; Kawarabayashi, Tatsuhiko; Kuroki, Masahide; Miyamoto, Shingo

    2010-08-01

    Advanced gastric cancer (GC) is one of the most lethal malignancies. Although many anticancer agents exist for the treatment of GC, its prognosis remains extremely poor. Therefore, further development of targeted therapies is required for patients with GC. To assess the role of heparin-binding epidermal growth factor-like growth factor (HB-EGF) as a target for GC therapy, the expression of EGF receptor ligands in GC cell lines, and the antitumor effects of an HB-EGF inhibitor (CRM197) as a single agent and in combination with other anticancer agents was assessed in GC cells. HB-EGF was the predominantly expressed ligand among EGF receptor ligands in all the cells. CRM197 induced significant cell apoptosis. Anticancer agents augmented the secretion of HB-EGF into the medium and simultaneously induced cell apoptosis. Combination of CRM197 with other anticancer agents significantly enhanced cell apoptosis. Additionally, co-administration of CRM197 and paclitaxel resulted in synergistic antitumor effects. These results suggested that HB-EGF is a rational target for GC therapy.

  3. Overview of Potential Clinical Applications of Hemoglobin Vesicles (HbV) as Artificial Red Cells, Evidenced by Preclinical Studies of the Academic Research Consortium

    PubMed Central

    Sakai, Hiromi

    2017-01-01

    Hemoglobin (Hb) is the most abundant protein in whole blood. This fact implies that the oxygen binding and releasing function of Hb is the most vital for sustaining life. All Hb is compartmentalized in red blood cells (RBCs) with corpuscular Hb concentration of about 35 g/dL, covered with a thin biomembrane. In spite of its abundance, Hb sometimes shows toxicity once it is leaked from RBCs. The shielding effect of the RBC membrane is physiologically important. Based on this structural importance, we have studied artificial red cells (Hb vesicles, HbV) as artificial oxygen carriers, which encapsulate a purified and concentrated Hb solution in phospholipid vesicles, mimicking the cellular structure of RBCs. Our academic research consortium has clarified the safety and efficacy of this HbV, aiming at clinical applications. Because of some superior characteristics to those of RBCs, HbV has the potential for use not only as a transfusion alternative but also for oxygen and carbon monoxide therapeutics, perfusate for transplant organs, and photosensitizer. In this review paper, such potential applications are summarized. PMID:28294960

  4. CAPABILITY TO RECOVER PLUTONIUM-238 IN H-CANYON/HB-LINE

    SciTech Connect

    Fuller, Kenneth S. Jr.; Smith, Robert H. Jr.; Goergen, Charles R.

    2013-01-09

    Plutonium-238 is used in Radioisotope Thermoelectric Generators (RTGs) to generate electrical power and in Radioisotope Heater Units (RHUs) to produce heat for electronics and environmental control for deep space missions. The domestic supply of Pu-238 consists of scrap material from previous mission production or material purchased from Russia. Currently, the United States has no significant production scale operational capability to produce and separate new Pu-238 from irradiated neptunium-237 targets. The Department of Energy - Nuclear Energy is currently evaluating and developing plans to reconstitute the United States capability to produce Pu-238 from irradiated Np-237 targets. The Savannah River Site had previously produced and/or processed all the Pu-238 utilized in Radioisotope Thermoelectric Generators (RTGs) for deep space missions up to and including the majority of the plutonium for the Cassini Mission. The previous full production cycle capabilities included: Np-237 target fabrication, target irradiation, target dissolution and Np-237 and Pu-238 separation and purification, conversion of Np-237 and Pu-238 to oxide, scrap recovery, and Pu-238 encapsulation. The capability and equipment still exist and could be revitalized or put back into service to recover and purify Pu-238/Np-237 or broken General Purpose Heat Source (GPHS) pellets utilizing existing process equipment in HB-Line Scrap Recovery, and H-anyon Frame Waste Recovery processes. The conversion of Np-237 and Pu-238 to oxide can be performed in the existing HB-Line Phase-2 and Phase-3 Processes. Dissolution of irradiated Np-237 target material, and separation and purification of Np-237 and Pu-238 product streams would be possible at production rates of ~ 2 kg/month of Pu-238 if the existing H-Canyon Frames Process spare equipment were re-installed. Previously, the primary H-Canyon Frames equipment was removed to be replaced: however, the replacement project was stopped. The spare equipment is

  5. Capability to Recover Plutonium-238 in H-Canyon/HB-Line - 13248

    SciTech Connect

    Fuller, Kenneth S. Jr.; Smith, Robert H. Jr.; Goergen, Charles R.

    2013-07-01

    Plutonium-238 is used in Radioisotope Thermoelectric Generators (RTGs) to generate electrical power and in Radioisotope Heater Units (RHUs) to produce heat for electronics and environmental control for deep space missions. The domestic supply of Pu-238 consists of scrap material from previous mission production or material purchased from Russia. Currently, the United States has no significant production scale operational capability to produce and separate new Pu-238 from irradiated neptunium-237 targets. The Department of Energy - Nuclear Energy is currently evaluating and developing plans to reconstitute the United States capability to produce Pu-238 from irradiated Np-237 targets. The Savannah River Site had previously produced and/or processed all the Pu-238 utilized in Radioisotope Thermoelectric Generators (RTGs) for deep space missions up to and including the majority of the plutonium for the Cassini Mission. The previous full production cycle capabilities included: Np- 237 target fabrication, target irradiation, target dissolution and Np-237 and Pu-238 separation and purification, conversion of Np-237 and Pu-238 to oxide, scrap recovery, and Pu-238 encapsulation. The capability and equipment still exist and could be revitalized or put back into service to recover and purify Pu-238/Np-237 or broken General Purpose Heat Source (GPHS) pellets utilizing existing process equipment in HB-Line Scrap Recovery, and H-Canyon Frame Waste Recovery processes. The conversion of Np-237 and Pu-238 to oxide can be performed in the existing HB-Line Phase-2 and Phase- 3 Processes. Dissolution of irradiated Np-237 target material, and separation and purification of Np-237 and Pu-238 product streams would be possible at production rates of ∼2 kg/month of Pu-238 if the existing H-Canyon Frames Process spare equipment were re-installed. Previously, the primary H-Canyon Frames equipment was removed to be replaced: however, the replacement project was stopped. The spare equipment

  6. Aldimine Formation Reaction, the First Step of the Maillard Early-phase Reaction, Might be Enhanced in Variant Hemoglobin, Hb Himeji.

    PubMed

    Koga, Masafumi; Inada, Shinya; Shimizu, Sayoko; Hatazaki, Masahiro; Umayahara, Yutaka; Nishihara, Eijun

    2015-01-01

    Hb Himeji (β140Ala→Asp) is known as a variant hemoglobin in which glycation is enhanced and HbA1c measured by immunoassay shows a high value. The phenomenon of enhanced glycation in Hb Himeji is based on the fact that the glycation product of variant hemoglobin (HbX1c) shows a higher value than HbA1c. In this study, we investigated whether aldimine formation reaction, the first step of the Maillard early-phase reaction, is enhanced in Hb Himeji in vitro. Three non-diabetic subjects with Hb Himeji and four non-diabetic subjects without variant hemoglobin were enrolled. In order to examine aldimine formation reaction, whole blood cells were incubated with 500 mg/dl of glucose at 37°C for 1 hour and were analyzed by high-performance liquid chromatography. Both HbA1c and HbX1c were not increased in this condition. After incubation with glucose, labile HbA1c (LA1c) fraction increased in the controls (1.1±0.3%). In subjects with Hb Himeji increases in the labile HbX1c (LX1c) fraction as well as the LA1c fraction were observed, and the degree of increase in the LX1c fraction was significantly higher than that of the LA1c fraction (1.8±0.1% vs. 0.5±0.2%, P<0.01). We have shown for the first time that aldimine (LX1c) formation reaction might be enhanced in Hb Himeji in vitro. The 140th amino acid in β chain of hemoglobin is suggested to be involved in aldimine formation reaction.

  7. Purification and some properties of cytochrome c-552 from an extreme thermophile, Thermus thermophilus HB8.

    PubMed

    Hon-Nami, K; Oshima, T

    1977-09-01

    A c-type cytochrome, cytochrome c-552, from a soluble fraction of an extreme thermophile, Thermus thermophilus HB8, was highly purified and its properties investigated. The absorption peaks were at 552, 522, and 417 nm in the reduced form, and at 408 nm in the oxidized form. The isoelectric point was at PH 10.8, the midpoint redox potential was about +0.23 V, and the molecular weight was about 15,000. The cytochrome c-552 was highly thermoresistant. The cytochrome reacted rapidly with pseudomonas aeruginosa nitrite reductase [EC 1.9.3.2], but slowly with bovine cytochrome oxidase [EC 1.9.3.1], yeast cytochrome c peroxidase [EC 1.11.1.5], or Nitrosomonas europaea hydroxylamine-cytochrome c reductase [EC 1.7.3.4].

  8. Congenital methemoglobinaemia due to Hb F-M-Fort Ripley in a preterm newborn.

    PubMed

    Ghotra, Satvinder; Jangaard, Krista; Pambrun, Chantale; Fernandez, Conrad Vincent

    2016-03-11

    Methemoglobinaemia is a rare cause of cyanosis in newborns. Congenital methemoglobinaemias due to M haemoglobin or deficiency of cytochrome b5 reductase are even rarer. We present a case of congenital methemoglobinaemia presenting at birth in a preterm infant. A baby boy born at 29 weeks and 3 days of gestation had persistent central cyanosis immediately after delivery, not attributable to a respiratory or cardiac pathology. Laboratory methemoglobin levels were not diagnostic. Cytochrome b5 reductase levels were normal and a newborn screen was unable to pick up any abnormal variants of fetal haemoglobin. Genetic testing showed a γ globin gene mutation resulting in the M haemoglobin, called Hb F-M-Fort Ripley. The baby had no apparent cyanosis at a corrected gestational age of 42 weeks. Although rare, congenital methaemoglobin aemia should be considered in the differential in a preterm with central cyanosis and investigated with genetic testing for γ globin chain mutations if other laboratory tests are non-conclusive.

  9. Phenotypic variability of Filipino beta(o)-thalassemia/HbE patients in Indonesia.

    PubMed

    Setianingsih, I; Williamson, R; Daud, D; Harahap, A; Marzuki, S; Forrest, S

    1999-09-01

    Three Indonesian patients with identical genotypes, each compound heterozygotes for Filipino beta(o)-thalassemia/HbE, expressed different clinical severities. One patient has mild disease and is transfusion independent, while the other two are severely affected and transfusion dependent. The size of the Filipino beta(o)-globin gene deletion was confirmed to be 45 kb, resolving conflicting values given in the literature. Neither ameliorating genetic factors such as alpha-globin gene deletions or the XmnI restriction site polymorphism at position -158 upstream of the (G)gamma-globin gene, nor differences in beta-globin gene haplotype, explain the phenotypic variation. These observations have implications for the development of antenatal diagnosis in Indonesia, as at present it is not possible to give an accurate prediction of severity of phenotype for this common genotype.

  10. Structure of 3-oxoacyl-(acyl-carrier protein) synthase II from Thermus thermophilus HB8

    SciTech Connect

    Bagautdinov, Bagautdin Ukita, Yoko; Miyano, Masashi; Kunishima, Naoki

    2008-05-01

    The crystal structure of 3-oxoacyl-(acyl-carrier protein) synthase II from T. thermophilus HB8 has been determined at 2.0 Å resolution and compared with the structures of β-keto-ACP synthases from other sources. The β-ketoacyl-(acyl carrier protein) synthases (β-keto-ACP synthases; KAS) catalyse the addition of two-carbon units to the growing acyl chain during the elongation phase of fatty-acid synthesis. As key regulators of bacterial fatty-acid synthesis, they are promising targets for the development of new antibacterial agents. The crystal structure of 3-oxoacyl-ACP synthase II from Thermus thermophilus HB8 (TtKAS II) has been solved by molecular replacement and refined at 2.0 Å resolution. The crystal is orthorhombic, space group P2{sub 1}2{sub 1}2, with unit-cell parameters a = 72.07, b = 185.57, c = 62.52 Å, and contains one homodimer in the asymmetric unit. The subunits adopt the well known α-β-α-β-α thiolase fold that is common to ACP synthases. The structural and sequence similarities of TtKAS II to KAS I and KAS II enzymes of known structure from other sources support the hypothesis of comparable enzymatic activity. The dimeric state of TtKAS II is important to create each fatty-acid-binding pocket. Closer examination of KAS structures reveals that compared with other KAS structures in the apo form, the active site of TtKAS II is more accessible because of the ‘open’ conformation of the Phe396 side chain.

  11. The Haber Bosch-harmful algal bloom (HB-HAB) link

    NASA Astrophysics Data System (ADS)

    Glibert, Patricia M.; Maranger, Roxane; Sobota, Daniel J.; Bouwman, Lex

    2014-10-01

    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 of N. Incorporation of these fertilizers into agricultural products is inefficient leading to significant environmental pollution and aquatic eutrophication. Of particular concern is the increased occurrence of harmful algal blooms (HABs) in waters receiving nutrient enriched runoff. Many phytoplankton causing HABs have physiological adaptive strategies that make them favored under conditions of elevated N : P conditions and supply of chemically reduced N (ammonium, urea). We propose that the HB-HAB link is a function of (1) the inefficiency of incorporation of N fertilizers in the food supply chain, the leakiness of the N cycle from crop to table, and the fate of lost N relative to P to the environment; and (2) adaptive physiology of many HABs to thrive in environments in which there is excess N relative to classic nutrient stoichiometric proportions and where chemically reduced forms of N dominate. The rate of HAB expansion is particularly pronounced in China where N fertilizer use has escalated very rapidly, where soil retention is declining, and where blooms have had large economic and ecological impacts. There, in addition to increased use of urea and high N : P based fertilizers overall, escalating aquaculture production adds to the availability of reduced forms of N, as does atmospheric deposition of ammonia. HABs in both freshwaters and marginal seas in China are highly related to these overall changing N loads and ratios. Without more aggressive N control the future outlook in terms of HABs is likely to include more events, more often, and they may also be more toxic.

  12. HB-LINE ANION EXCHANGE PURIFICATION OF AFS-2 PLUTONIUM FOR MOX

    SciTech Connect

    Kyser, E. A.; King, W. D.

    2012-07-31

    Non-radioactive cerium (Ce) and radioactive plutonium (Pu) anion exchange column experiments using scaled HB-Line designs were performed to investigate the feasibility of using either gadolinium nitrate (Gd) or boric acid (B as H{sub 3}BO{sub 3}) as a neutron poison in the H-Canyon dissolution process. Expected typical concentrations of probable impurities were tested and the removal of these impurities by a decontamination wash was measured. Impurity concentrations are compared to two specifications - designated as Column A or Column B (most restrictive) - proposed for plutonium oxide (PuO{sub 2}) product shipped to the Mixed Oxide (MOX) Fuel Fabrication Facility (MFFF). Use of Gd as a neutron poison requires a larger volume of wash for the proposed Column A specification. Since boron (B) has a higher proposed specification and is more easily removed by washing, it appears to be the better candidate for use in the H-Canyon dissolution process. Some difficulty was observed in achieving the Column A specification due to the limited effectiveness that the wash step has in removing the residual B after ~4 BV's wash. However a combination of the experimental 10 BV's wash results and a calculated DF from the oxalate precipitation process yields an overall DF sufficient to meet the Column A specification. For those impurities (other than B) not removed by 10 BV's of wash, the impurity is either not expected to be present in the feedstock or process, or recommendations have been provided for improvement in the analytical detection/method or validation of calculated results. In summary, boron is recommended as the appropriate neutron poison for H-Canyon dissolution and impurities are expected to meet the Column A specification limits for oxide production in HB-Line.

  13. HB-LINE ANION EXCHANGE PURIFICATION OF AFS-2 PLUTONIUM FOR MOX

    SciTech Connect

    Kyser, E.; King, W.

    2012-04-25

    Non-radioactive cerium (Ce) and radioactive plutonium (Pu) anion exchange column experiments using scaled HB-Line designs were performed to investigate the feasibility of using either gadolinium nitrate (Gd) or boric acid (B as H{sub 3}BO{sub 3}) as a neutron poison in the H-Canyon dissolution process. Expected typical concentrations of probable impurities were tested and the removal of these impurities by a decontamination wash was measured. Impurity concentrations are compared to two specifications - designated as Column A or Column B (most restrictive) - proposed for plutonium oxide (PuO{sub 2}) product shipped to the Mixed Oxide (MOX) Fuel Fabrication Facility (MFFF). Use of Gd as a neutron poison requires a larger volume of wash for the proposed Column A specification. Since boron (B) has a higher proposed specification and is more easily removed by washing, it appears to be the better candidate for use in the H-Canyon dissolution process. Some difficulty was observed in achieving the Column A specification due to the limited effectiveness that the wash step has in removing the residual B after {approx}4 BV's wash. However a combination of the experimental 10 BV's wash results and a calculated DF from the oxalate precipitation process yields an overall DF sufficient to meet the Column A specification. For those impurities (other than B) not removed by 10 BV's of wash, the impurity is either not expected to be present in the feedstock or process, or recommendations have been provided for improvement in the analytical detection/method or validation of calculated results. In summary, boron is recommended as the appropriate neutron poison for H-Canyon dissolution and impurities are expected to meet the Column A specification limits for oxide production in HB-Line.

  14. CALIBRATION OF THE HB LINE ACTIVE WELL NEUTRON COINCIDENCE COUNTER FOR MEASUREMENT OF LANL 3013 HIGHLY ENRICHED URANIUM PRODUCT SPLITS

    SciTech Connect

    Dewberry, R; Donald02 Williams, D; Rstephen Lee, R; David-W Roberts, D; Leah Arrigo, L

    2008-01-22

    In this paper we describe set-up, calibration, and testing of the F-Area Analytical Labs active well neutron coincidence counter(HV-221000-NDA-X-1-DK-AWCC-1)in SRNL for use in HB-Line to enable assay of 3013EU/Pu metal product. The instrument was required within a three-month window for availability upon receipt of LANL Category IV uranium oxide samples into the SRS HB-Line facility. We describe calibration of the instrument in the SRNL nuclear nondestructive assay facility in the range 10-400 g HEU for qualification and installation in HB-Line for assay of the initial suite of product samples.

  15. Coexistence of superconductivity and commensurate charge density wave in 4Hb-TaS2-xSex single crystals

    NASA Astrophysics Data System (ADS)

    Liu, Y.; Li, L. J.; Lu, W. J.; Ang, R.; Liu, X. Z.; Sun, Y. P.

    2014-01-01

    The transition-metal dichalcogenides, a family of graphene-like two-dimensional (2D) materials, exhibit exciting properties for potential applications and fundamental researches. We successfully fabricated a new series of 4Hb-TaS2-xSex (0 ≤ x ≤ 1.5) single crystals by chemical vapor transport technique. This is the first time to demonstrate the coexistence of superconductivity and commensurate charge density wave (CCDW) in 4Hb-TaS2-xSex (0 ≤ x ≤ 1.5). The evolution of the electronic states tuned by Se-doping are also exhibited in the phase diagram. Taking into account the special crystal structure of 4Hb-TaS2-xSex (0 ≤ x ≤ 1.5), we draw a conclusion that the H- and T-layers play a crucial role to dominate the state of superconductivity and CCDW, respectively.

  16. HbA1c as a Screening tool for Ketosis in Patients with Type 2 Diabetes Mellitus

    PubMed Central

    Zhu, Bing; Bu, Le; Zhang, Manna; Gusdon, Aaron M.; Zheng, Liang; Rampersad, Sharvan; Li, Jue; Qu, Shen

    2016-01-01

    Ketosis in patients with type 2 diabetes mellitus (T2DM) is overlooked due to atypical symptoms. The objective of this study is to evaluate the value of hemoglobin A1c (HbA1c) as a screening tool for ketosis in T2DM patients. This retrospective study consisted of 253 T2DM patients with ketosis at Shanghai 10th People’s Hospital during a period from January 1, 2011 to June 30, 2015. A control group consisted of 221 T2DM patients without ketosis randomly selected from inpatients during the same period. Receiver operating characteristic curve (ROC) analysis was used to examine the sensitivity and specificity of HbA1c as an indicator for ketosis. Higher HbA1c levels were correlated with ketosis. In patients with newly diagnosed T2DM, the area under the curve (AUC) was 0.832, with 95% confidence interval (CI) 0.754–0.911. The optimal threshold was 10.1% (87 mmol/mol). In patients with previously diagnosed T2DM, the AUC was 0.811 (95% CI: 0.767–0.856), with an optimal threshold of 8.6% (70 mmol/mol). HbA1c is a potential screening tool for ketosis in patients with T2DM. Ketosis is much more likely with HbA1c values at ≥10.1% in patients with newly diagnosed T2DM and HbA1c values at ≥8.6% in patients with previously diagnosed T2DM. PMID:28009017

  17. A Swiss family with hemoglobin P Galveston beta117His leads to Arg, including two patients with hb P/beta thalassemia.

    PubMed

    Di Iorio, E E; Winterhalter, K H; Wilson, K; Rosenmund, A; Marti, H R

    1975-08-01

    The mutant Hb P Galveston (beta117His leads to Arg) is observed in two heterozygotes for beta thalassemia and by itself does not cause clinical symptoms. Some of the physico-chemical properties of Hb P Galveston are identical to the onemical properties of Hb P Galveston are identical to the ones hemoglobin Zurich (beta 63 His leads to Arg) so that only a detailed analysis led to its proper identification.

  18. A rare haemoglobin variant (Hb Phnom Penh) manifesting as a falsely high haemoglobin A1c value on ion-exchange chromatography.

    PubMed

    Chen, Chi-Fen; Tai, Yen-Kuang

    2014-08-01

    Most haemoglobin (Hb) variants are clinically silent. However, some Hb variants may interfere with the measurement of haemoglobin A1c (HbA1c), resulting in spurious values depending on the assays used. We herein report the case of a 53-year-old Taiwanese man with type 2 diabetes mellitus, who presented with an abnormal HbA1c peak on ion-exchange chromatography. Additional investigations, including intensified self-monitored blood glucose tests, an alternative HbA1c assay, and a glycaemic indicator based on a different method, revealed that the HbA1c values were falsely elevated. Subsequent DNA analysis confirmed that the patient was heterozygous for the insertion of an isoleucine residue at codons 117/118 of the a1-globin gene, Hb Phnom Penh. Clinical laboratorians should be aware of the interfering factors in their HbA1c analysis. Cautious inspection of the chromatogram may provide a valuable clue to the presence of an Hb variant.

  19. Hematological and Molecular Characterization of Hb J-Buda [α61(E10)Lys → Asn, AAG > AAT].

    PubMed

    Panyasai, Sitthichai; Permsripong, Nopphadol; Jaiping, Kanokwan; Khantarag, Pisuttinee; Pornprasert, Sakorn

    2016-06-01

    Hemoglobin (Hb) J-Buda [α61(E10)Lys → Asn, AAG > AAT] is a very rare α-chain variant found in South-East Asia. We analyzed hematological parameters and provided a rapid molecular analysis method for detection of this hemoglobinopathy in two Thai women who had severe microcytic anemia with Hb and MCV <70 g/L and 80 fL, respectively. The HPLC revealed an abnormal Hb peak eluted ahead of HbA at retention time of 1.91-1.98 min. On CE, the abnormal Hb peak was observed at the electrophoretic zone 12 which corresponded to Hb Bart's. The DNA sequencing revealed the AAG → AAT mutation at codon 61 for Hb J-Buda on one allele of the α1-globin gene. The developed Allele-specific PCR (ASPCR) showed the 455 bp amplified fragment from Hb J-Buda allele. Thus, understanding of hematological characterizations and the developed ASPCR for diagnosis of Hb J-Buda are essential for genetic counseling of this hemoglobinopathy.

  20. Site-directed mutagenesis of heparin-binding EGF-like growth factor (HB-EGF): analysis of O-glycosylation sites and properties.

    PubMed

    Davis-Fleische, K M; Brigstock, D R; Besner, G E

    2001-01-01

    Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a 22 kDa, O-glycosylated protein. HeLa cells infected with a recombinant vaccinia virus expressing human HB-EGF produced a secreted, bioactive protein, with Mr 22,000 that was decreased to 14,000 by treatment with O-glycanase. Site-directed mutagenesis of HB-EGF cDNA using oligonucleotide- and PCR-directed techniques was performed to change the potential glycosylation sites, Thr75 and Thr85, to alanine residues to prevent O-glycosylation. Purification and characterization of the mutant proteins demonstrated that: (i) both O-glycosylation sites of HB-EGF are utilized, (ii) HB-EGF secretion does not require O-glycosylation, (iii) removal of O-glycans does not affect proteolytic cleavage of the HB-EGF precursor, nor does it influence HB-EGF intracellular trafficking or subcellular localization, and (iv) HB-EGF produced by HeLa cells is heavily sialylated. Comparisons between glycosylation mutants and wild-type HB-EGF revealed no significant apparent differences in receptor binding activity.

  1. HB 2578--Relating to the School Meals Program. Testimony, 79th Texas State Legislature (April 26, 2005)

    ERIC Educational Resources Information Center

    Hagert, Celia

    2005-01-01

    The Center for Public Policy Priorities supports HB 2574. Why encourage school districts to offer free meals to all students? The link between adequate nutrition and improved academic performance creates a clear incentive for Texas to increase participation in the school breakfast and lunch programs, particularly among low-income children.…

  2. Hot HB Stars in Globular Clusters: Physical Parameters and Consequences for Theory. 5; Radiative Levitation Versus Helium Mixing

    NASA Technical Reports Server (NTRS)

    Moehler, S.; Sweigart, A. V.; Landsman, W. B.; Heber, U.

    2000-01-01

    Atmospheric parameters (T(sub eff), log g), masses and helium abundances are derived for 42 hot horizontal branch (HB) stars in the globular cluster NGC6752. For 19 stars we derive magnesium and iron abundances as well and find that iron is enriched by a factor of 50 on average with respect to the cluster abundance whereas the magnesium abundances are consistent with the cluster abundance. Radiation pressure may levitate heavy elements like iron to the surface of the star in a diffusive process. Taking into account the enrichment of heavy elements in our spectroscopic analyses we find that high iron abundances can explain part, but not all, of the problem of anomalously low gravities along the blue HB. The blue HB stars cooler than about 15,100 K and the sdB stars (T(sub eff) greater than or = 20,000 K) agree well with canonical theory when analysed with metal-rich ([M/H] = +0.5) model atmospheres, but the stars in between these two groups remain offset towards lower gravities and masses. Deep Mixing in the red giant progenitor phase is discussed as another mechanism that may influence the position of the blue HB stars in the (T(sub eff), log g)-plane but not their masses.

  3. The role of the PHP domain associated with DNA polymerase X from Thermus thermophilus HB8 in base excision repair.

    PubMed

    Nakane, Shuhei; Nakagawa, Noriko; Kuramitsu, Seiki; Masui, Ryoji

    2012-11-01

    Base excision repair (BER) is one of the most commonly used DNA repair pathways involved in genome stability. X-family DNA polymerases (PolXs) play critical roles in BER, especially in filling single-nucleotide gaps. In addition to a polymerase core domain, bacterial PolXs have a polymerase and histidinol phosphatase (PHP) domain with phosphoesterase activity which is also required for BER. However, the role of the PHP domain of PolX in bacterial BER remains unresolved. We found that the PHP domain of Thermus thermophilus HB8 PolX (ttPolX) functions as two types of phosphoesterase in BER, including a 3'-phosphatase and an apurinic/apyrimidinic (AP) endonuclease. Experiments using T. thermophilus HB8 cell lysates revealed that the majority of the 3'-phosphatase and AP endonuclease activities are attributable to the another phosphoesterase in T. thermophilus HB8, endonuclease IV (ttEndoIV). However, ttPolX possesses significant 3'-phosphatase activity in ΔttendoIV cell lysate, indicating possible complementation. Our experiments also reveal that there are only two enzymes that display the 3'-phosphatase activity in the T. thermophilus HB8 cell, ttPolX and ttEndoIV. Furthermore, phenotypic analysis of ΔttpolX, ΔttendoIV, and ΔttpolX/ΔttendoIV using hydrogen peroxide and sodium nitrite supports the hypothesis that ttPolX functions as a backup for ttEndoIV in BER.

  4. Haematological parameters and HbA2 levels in beta-thalassaemia trait with coincident iron deficiency.

    PubMed

    Madan, N; Sikka, M; Sharma, S; Rusia, U

    1998-07-01

    Iron status was estimated in 463 heterozygous beta-thalassaemics to delineate the effect of iron deficiency (ID) on the haematological parameters and expression of HbA2 in these patients. One hundred and twenty six (27.2%) traits had coincident ID. These iron deficient traits had a significantly (p < 0.0002), higher prevalence of anaemia (90.5%) as compared to iron replete traits (71.5%). Mean haemoglobin concentration was significantly lower (p < 0.0001) in beta-thalassaemics with ID (10.7 +/- 1.5) g/al as compared to those without ID (11.6 +/- 1.6 g/dl). Mean MCV and MCH were significantly lowered (p < 0.0001) in patients of beta-thalassaemia trait (BTT) with ID than in these without ID. Mean HbA2 was not significantly different in the two groups of traits and was elevated (> or = 3.5%) in all except one patient. However, mean HbA2/cell was significantly (p < 0.05) lower in traits with ID. The effect of ID in BTT was apparent with significant lowering of haemoglobin concentration and increased prevalence of anaemia. Iron therapy is warranted in iron deficient traits and would help in significantly raising their haemoglobin concentration. Elevation in HbA2 values was striking and could be used with reliability for diagnosis of BTT even in the presence of ID.

  5. Proteasome inhibition induces both antioxidant and hb f responses in sickle cell disease via the nrf2 pathway.

    PubMed

    Pullarkat, Vinod; Meng, Zhuo; Tahara, Stanley M; Johnson, Cage S; Kalra, Vijay K

    2014-01-01

    Oxidant stress is implicated in the manifestations of sickle cell disease including hemolysis and vascular occlusion. Strategies to induce antioxidant response as well as Hb F (α2γ2) have the potential to ameliorate the severity of sickle cell disease. Nuclear factor (erythroid-derived 2)-like 2 (NFE2L2 or Nrf2) is a transcription factor that regulates antioxidant enzymes as well as γ-globin transcription. The Nrf2 in the cytoplasm is bound to its adapter protein Keap-1 that targets Nrf2 for proteasomal degradation, thereby preventing its nuclear translocation. We examined whether inhibiting the 26S proteasome using the clinically applicable proteasome inhibitors bortezomib and MLN 9708 would promote nuclear translocation of Nrf2, and thereby induce an antioxidant response and as well as Hb F in sickle cell disease. Proteasome inhibitors induced reactive oxygen species (ROS) and thereby increased Nrf2-dependent antioxidant enzyme transcripts, elevated cellular glutathione (GSH) levels and γ-globin transcripts as well as Hb F levels in the K562 cell line and also in erythroid burst forming units (BFU-E) generated from peripheral blood mononuclear cells of sickle cell disease patients. These responses were abolished by siRNA-mediated knockdown of Nrf2. Proteasome inhibitors, especially newer oral agents such as MLN9708 have the potential to be readily translated to clinical trials in sickle cell disease with the dual end points of antioxidant response and Hb F induction.

  6. Auxin Response Factor2 (ARF2) and Its Regulated Homeodomain Gene HB33 Mediate Abscisic Acid Response in Arabidopsis

    PubMed Central

    Wang, Li; Hua, Deping; He, Junna; Duan, Ying; Chen, Zhizhong; Hong, Xuhui; Gong, Zhizhong

    2011-01-01

    The phytohormone abscisic acid (ABA) is an important regulator of plant development and response to environmental stresses. In this study, we identified two ABA overly sensitive mutant alleles in a gene encoding Auxin Response Factor2 (ARF2). The expression of ARF2 was induced by ABA treatment. The arf2 mutants showed enhanced ABA sensitivity in seed germination and primary root growth. In contrast, the primary root growth and seed germination of transgenic plants over-expressing ARF2 are less inhibited by ABA than that of the wild type. ARF2 negatively regulates the expression of a homeodomain gene HB33, the expression of which is reduced by ABA. Transgenic plants over-expressing HB33 are more sensitive, while transgenic plants reducing HB33 by RNAi are more resistant to ABA in the seed germination and primary root growth than the wild type. ABA treatment altered auxin distribution in the primary root tips and made the relative, but not absolute, auxin accumulation or auxin signal around quiescent centre cells and their surrounding columella stem cells to other cells stronger in arf2-101 than in the wild type. These results indicate that ARF2 and HB33 are novel regulators in the ABA signal pathway, which has crosstalk with auxin signal pathway in regulating plant growth. PMID:21779177

  7. 75 FR 80545 - Carolina Power & Light Company; H.B. Robinson Steam Electric Plant, Unit No. 2; Environmental...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-22

    ... COMMISSION Carolina Power & Light Company; H.B. Robinson Steam Electric Plant, Unit No. 2; Environmental..., ``Physical protection of plants and materials,'' for Facility Operating License No. DPR-23, issued to Carolina Power & Light Company (the licensee), for operation of the H. B. Robinson Steam Electric...

  8. Role of Altered Venous Blood Lactate and HbA1c in Women with Gestational Diabetes Mellitus

    PubMed Central

    Santhosh, N U; Krishnamurthy, N; Chethan, Chethana; Shilpashree, M K

    2016-01-01

    Introduction Being a mirror image of metabolic syndrome, Gestational Diabetes Mellitus (GDM) is associated with significant maternal and fetal morbidity. Increased blood lactate concentration and alterations of substrate utilization are partly involved in development of insulin resistance in GDM. Fetuses born to such mothers have shown low umbilical vein oxygen saturation and low oxygen content and increased lactate concentrations. These changes may certainly reflect enhanced fetal metabolism as a result of hyperglycaemia and hyperinsulinemia and therefore, these fetuses deserve intense surveillance at term and during delivery. Ideally, HbA1c should be maintained below 5% during their first trimesters and below 6% during third trimester. We planned to investigate GDM women for their HbA1c levels too. Aim To know if there is any alteration in blood lactate and/or HbA1c levels and to know if there is any correlation between these two parameters in GDM pregnancies, in comparison with the previous studies which measured lactate in cord blood and placental vessels of GDM women. Materials and Methods It was a hospital based prospective study on 40 women with gestational diabetes and 40 age-matched normal pregnant women. We analysed the biochemical and metabolic mileau in these women by estimating venous blood lactate and HbA1c levels. We paid special attention to follow them up regarding maternal complications if any and perinatal outcomes. The independent samples t-test and Pearson’s correlation test were applied. Results GDM mothers showed significantly higher lactate and HbA1c levels than normal pregnant women, both with p<0.001. Blood pressure and fetal birth weight were also significantly higher in GDM group than Normal Pregnant (NP) group, both with p-values of <0.001. Further, this increased lactate levels showed significant positive correlation with HbA1c, blood pressure and fetal birth weight. Conclusion Maternal blood lactate and HbA1c levels have a

  9. Effect of ethnicity on HbA1c levels in individuals without diabetes: Systematic review and meta-analysis

    PubMed Central

    Freitas, Priscila Aparecida Correa; Gross, Jorge Luiz

    2017-01-01

    Aims/Hypothesis Disparities in HbA1c levels have been observed among ethnic groups. Most studies were performed in patients with diabetes mellitus (DM), which may interfere with results due to the high variability of glucose levels. We conducted a systematic review and meta-analysis to investigate the effect of ethnicity on HbA1c levels in individuals without DM. Methods This is a systematic review with meta-analysis. We searched MEDLINE and EMBASE up to September 2016. Studies published after 1996, performed in adults without DM, reporting HbA1c results measured by certified/standardized methods were included. A random effects model was used and the effect size was presented as weighted HbA1c mean difference (95% CI) between different ethnicities as compared to White ethnicity. Results Twelve studies met the inclusion criteria, totalling data from 49,238 individuals. There were significant differences between HbA1c levels in Blacks [0.26% (2.8 mmol/mol); 95% CI 0.18 to 0.33 (2.0 to 3.6), p <0.001; I2 = 90%, p <0.001], Asians [0.24% (2.6 mmol/mol); 95% CI 0.16 to 0.33 (1.7 to 3.6), p <0.001; I2 = 80%, p = 0.0006] and Latinos [0.08% (0.9 mmol/mol); IC 95% 0.06 to 0.10 (0.7 to 1.1); p <0.001; I2 = 0%; p = 0.72] when compared to Whites. Conclusions/Interpretation This meta-analysis shows that, in individuals without DM, HbA1c values are higher in Blacks, Asians, and Latinos when compared to White persons. Although small, these differences might have impact on the use of a sole HbA1c point to diagnose DM in all ethnic populations. PMID:28192447

  10. Cloning and characterization of HbMT2a, a metallothionein gene from Hevea brasiliensis Muell. Arg differently responds to abiotic stress and heavy metals

    SciTech Connect

    Li, Yan; Chen, Yue Yi; Yang, Shu Guang; Tian, Wei Min

    2015-05-22

    Metallothioneins (MTs) are of low molecular mass, cysteine-rich proteins. They play an important role in the detoxification of heavy metals and homeostasis of intracellular metal ions, and protecting against intracellular oxidative damages. In this study a full-length cDNA of type 2 plant metallothioneins, HbMT2a, was isolated from 25 mM Polyethyleneglycol (PEG) stressed leaves of Hevea brasiliensis by RACE. The HbMT2a was 372 bp in length and had a 237 bp open reading frame (ORF) encoding for a protein of 78 amino acid residues with molecular mass of 7.772 kDa. The expression of HbMT2a in the detached leaves of rubber tree clone RY7-33-97 was up-regulated by Me-JA, ABA, PEG, H{sub 2}O{sub 2}, Cu{sup 2+} and Zn{sup 2+}, but down-regulated by water. The role of HbMT2a protein in protecting against metal toxicity was demonstrated in vitro. PET-28a-HbMT2-beared Escherichia coli. Differential expression of HbMT2a upon treatment with 10 °C was observed in the detached leaves of rubber tree clone 93-114 which is cold-resistant and Reken501 which is cold-sensitive. The expression patterns of HbMT2a in the two rubber tree clones may be ascribed to a change in the level of endogenous H{sub 2}O{sub 2}. - Highlights: • Cloning an HbMT2a gene from rubber tree. • Analyzing expression patterns of HbMT2a upon abiotic stress and heavy metal stress. • Finding different expression patterns of HbMT2a among two Hevea germplasm. • The expressed protein of HbMT2a enhances copper and zinc tolerance in Escherichia coli.

  11. The Change in HbA1c Associated with Initial Adherence and Subsequent Change in Adherence among Diabetes Patients Newly Initiating Metformin Therapy.

    PubMed

    Nichols, Gregory A; Rosales, A Gabriela; Kimes, Teresa M; Tunceli, Kaan; Kurtyka, Karen; Mavros, Panagiotis

    2016-01-01

    Introduction. Whether changes in adherence are associated with changes in HbA1c is assumed but not known. Methods. We conducted a observational study of 2,844 type 2 diabetes patients who initiated metformin as their first antihyperglycemic drug. Using HbA1c measures before, 6-12 months after, and up to 3 years after metformin initiation, we analyzed HbA1c change as a function of initial adherence and change in adherence. Results. Compared with no adherence, initial adherence of 50-79% was associated with an adjusted reduction in HbA1c of 0.45% while adherence ≥80% was associated with HbA1c reduction of 0.73%. Change from some initial adherence (1-79%) to total nonadherence was associated with 0.25% increase in HbA1c. Change from some to full adherence was associated with an HbA1c decrease of 0.15%. Those associations were accentuated among patients not in glycemic control: change from some to no adherence was associated with an HbA1c increase of 0.63% and change from some to full adherence was associated with an HbA1c decrease of 0.40%. Conclusions. Initial adherence to newly prescribed metformin therapy produces substantial HbA1c reduction. Among those with modest adherence but suboptimal glycemic control, the difference between moving to full adherence versus nonadherence results in lower HbA1c of one percentage point.

  12. Effect of low glycemic load diet on glycated hemoglobin (HbA1c) in poorly-controlled diabetes patients.

    PubMed

    Ziaee, Amir; Afaghi, Ahmad; Sarreshtehdari, Majied

    2011-12-29

    Different carbohydrate diets have been administrated to diabetic patients to evaluate the glycemic response, while Poor-controlled diabetes is increasing world wide. To investigate the role of an alternative carbohydrate diet on glycemic control, we explored the effect of a low glycemic load (Low GL)-high fat diet on glycemic response and also glycated hemoglobin (HbA1c) of poor-controlled diabetes patients. Hundred poorly-controlled diabetes patients, HbA1c > 8, age 52.8 ± 4.5 y, were administrated a low GL diet , GL = 67 (Energy 1800 kcal; total fat 36%; fat derived from olive oil and nuts 15%; carbohydrate 42%; protein 22%) for 10 weeks. Patients did their routine life style program during intervention. Fasting blood glucose and HbA1c before and after intervention with significant reduction were: 169 ± 17, 141 ± 12; 8.85% (73 mmol/mol) ± 0.22%, and 7.81% (62 mmol/mol) ± 0.27%; respectively (P < 0.001). Mean fasting blood glucose reduced by 28.1 ± 12.5 and HbA1c by 1.1% (11 mmol/mol) ± 0.3% (P=0.001). There was positive moderate correlation between HbA1c concentration before intervention and FBS reduction after intervention (P < 0.001, at 0.01 level, R =0.52), and strong positive correlation between FBS before intervention and FBS reduction (P < 0.001, at 0.01 level, R = 0.70). This study demonstrated that our alternative low glycemic load diet can be effective in glycemic control.

  13. The clinical significance of K-Cl cotransport activity in red cells of patients with HbSC disease.

    PubMed

    Rees, David C; Thein, Swee Lay; Osei, Anna; Drasar, Emma; Tewari, Sanjay; Hannemann, Anke; Gibson, John S

    2015-05-01

    HbSC disease is the second commonest form of sickle cell disease, with poorly understood pathophysiology and few treatments. We studied the role of K-Cl cotransport activity in determining clinical and laboratory features, and investigated its potential role as a biomarker. Samples were collected from 110 patients with HbSC disease and 41 with sickle cell anemia (HbSS). K-Cl cotransport activity was measured in the oxygenated (K-Cl cotransport(100)) and deoxygenated (K-Cl cotransport(0)) states, using radioactive tracer studies. K-Cl cotransport activity was high in HbSC and decreased significantly on deoxygenation. K-Cl cotransport activity correlated significantly and positively with the formation of sickle cells. On multiple regression analysis, K-Cl cotransport increased significantly and independently with increasing reticulocyte count and age. K-Cl cotransport activity was increased in patients who attended hospital with acute pain in 2011 compared to those who did not (K-Cl cotransport(100): mean 3.87 versus 3.20, P=0.009, independent samples T-test; K-Cl cotransport(0): mean 0.96 versus 0.68, P=0.037). On logistic regression only K-Cl cotransport was associated with hospital attendance. Increased K-Cl cotransport activity was associated with the presence of retinopathy, but this effect was confounded by age. This study links variability in a fundamental aspect of cellular pathology with a clinical outcome, suggesting that K-Cl cotransport is central to the pathology of HbSC disease. Increased K-Cl cotransport activity is associated with increasing age, which may be of pathophysiological significance. Effective inhibition of K-Cl cotransport activity is likely to be of therapeutic benefit.

  14. Dietary patterns associated with HbA1c and LDL cholesterol among individuals with type 1 diabetes in China

    PubMed Central

    Jaacks, Lindsay M.; Crandell, Jamie; Mendez, Michelle A.; Lamichhane, Archana P.; Liu, Wei; Ji, Linong; Du, Shufa; Rosamond, Wayne; Popkin, Barry M.; Mayer-Davis, Elizabeth J.

    2015-01-01

    Aims To identify dietary patterns that influence cardiometabolic risk among individuals with type 1 diabetes (T1D) in China. Methods Data are from a cross-sectional study of T1D in China (n=99). Dietary intake was assessed using three 24-hour recalls. Reduced rank regression was used to identify dietary patterns from a set of 20 food groups that maximized the explained variation in glycated hemoglobin A1c (HbA1c) and low-density lipoprotein (LDL) cholesterol. Results Dietary pattern 1 was characterized by low intakes of wheat products and high-fat cakes, and high intakes of beans and pickled vegetables. Dietary pattern 2 was characterized by low intakes of high-fat cakes, nuts/seeds, fish/shellfish, and teas/coffee, and high intakes of rice and eggs. Participants in the highest tertile of dietary pattern 1 had significantly (p<0.05) higher HbA1c and LDL cholesterol compared to participants in the lowest tertile: mean difference in HbA1c was 1.0 percentage point (11mmol/mol) and in LDL cholesterol was 0.36 mmol/L after adjustment for age and household income. Dietary pattern 2 was not associated with HbA1c or LDL cholesterol. Conclusions We identified a dietary pattern that is significantly related to HbA1c and LDL cholesterol. These findings provide support for behavioral strategies to prevent complications in individuals with T1D in China. PMID:25630525

  15. dbx mediates neuronal specification and differentiation through cross-repressive, lineage-specific interactions with eve and hb9.

    PubMed

    Lacin, Haluk; Zhu, Yi; Wilson, Beth A; Skeath, James B

    2009-10-01

    Individual neurons adopt and maintain defined morphological and physiological phenotypes as a result of the expression of specific combinations of transcription factors. In particular, homeodomain-containing transcription factors play key roles in determining neuronal subtype identity in flies and vertebrates. dbx belongs to the highly divergent H2.0 family of homeobox genes. In vertebrates, Dbx1 and Dbx2 promote the development of a subset of interneurons, some of which help mediate left-right coordination of locomotor activity. Here, we identify and show that the single Drosophila ortholog of Dbx1/2 contributes to the development of specific subsets of interneurons via cross-repressive, lineage-specific interactions with the motoneuron-promoting factors eve and hb9 (exex). dbx is expressed primarily in interneurons of the embryonic, larval and adult central nervous system, and these interneurons tend to extend short axons and be GABAergic. Interestingly, many Dbx(+) interneurons share a sibling relationship with Eve(+) or Hb9(+) motoneurons. The non-overlapping expression of dbx and eve, or dbx and hb9, within pairs of sibling neurons is initially established as a result of Notch/Numb-mediated asymmetric divisions. Cross-repressive interactions between dbx and eve, and dbx and hb9, then help maintain the distinct expression profiles of these genes in their respective pairs of sibling neurons. Strict maintenance of the mutually exclusive expression of dbx relative to that of eve and hb9 in sibling neurons is crucial for proper neuronal specification, as misexpression of dbx in motoneurons dramatically hinders motor axon outgrowth.

  16. Is Hb A2 elevated in adults with sickle-alpha-thalassemia (beta(S)/beta(S); -alpha/-alpha)?

    PubMed

    Ballas, S K; Gay, R N; Chehab, F F

    1997-09-01

    Thirteen patients with sickle cell anemia (SS) were found to have two alpha gene deletions with a presumptive genotype of beta(S)/beta(S); -alpha/-alpha. Hematological data showed that this group of patients had elevated Hb A2 level. In order to determine whether the elevation of Hb A2 is typical of SS with a two alpha gene deletion or is due to undiagnosed S-beta(O)-thalassemia with a two alpha gene deletion we looked for the presence or absence of beta(O)-thalassemia by molecular techniques. The latter included reverse dot-blot hybridization to rule out a beta-thalassemia mutation, digestion with CvnI endonuclease followed by Southern blotting and hybridization with a beta genomic probe, and, in selected patients, determination of the synthetic alpha/beta ratio. One of the 13 patients had S-beta(O)-thalassemia with a G-->A mutation at IVS-II-1 indicating that her genotype was beta(S)/beta(O) thalassemia; -alpha/-alpha. The remaining 12 patients were homozygous for the sickle gene, had relatively elevated Hb levels, increased Hb A2 values, and Hb F levels similar to those in patients with SS and four or three alpha genes. At the clinical level, the 12 patients with SS and a two alpha gene deletion had increased prevalence of avascular necrosis, retinopathy, and splenomegaly, but decreased prevalence of leg ulcers and cerebrovascular accidents. Together, the data indicate that SS with a two alpha gene deletion (beta(S)/beta(S); -alpha/-alpha) is a unique subset of patients with SS characterised by distinct hematological and clinical features.

  17. Crystal structure of a major outer membrane protein from Thermus thermophilus HB27.

    PubMed

    Brosig, Alexander; Nesper, Jutta; Boos, Winfried; Welte, Wolfram; Diederichs, Kay

    2009-02-06

    The thermophilic eubacterium Thermus thermophilus belongs to one of the oldest branches of evolution and has a multilayered cell envelope that differs from that of modern Gram-negative bacteria. Its outer membrane contains integral outer membrane proteins (OMPs), of which only a few are characterized. TtoA, a new beta-barrel OMP, was identified by searching the genome sequence of strain HB27 for the presence of a C-terminal signature sequence. The structure of TtoA was determined to a resolution of 2.8 A, representing the first crystal structure of an OMP from a thermophilic bacterium. TtoA consists of an eight-stranded beta-barrel with a large extracellular part to which a divalent cation is bound. A five-stranded extracellular beta-sheet protrudes out of the membrane-embedded transmembrane barrel and is stabilized by a disulfide bridge. The edge of this beta-sheet forms crystal contacts that could mimic interactions with other proteins. In modern Gram-negative bacteria, the C-terminal signature sequence of OMPs is required for binding to an Omp85 family protein as a prerequisite for its assembly. We present hints that a similar assembly pathway exists in T. thermophilus by an in vitro binding assay, where unfolded TtoA binds to the Thermus Omp85 family protein TtOmp85, while a mutant without the signature sequence does not.

  18. Structure of indole-3-glycerol phosphate synthase from Thermus thermophilus HB8: implications for thermal stability.

    PubMed

    Bagautdinov, Bagautdin; Yutani, Katsuhide

    2011-12-01

    The three-dimensional structure of indole-3-glycerol phosphate synthase (IGPS) from the thermophilic bacterium Thermus thermophilus HB8 (TtIGPS) has been determined at 1.8 Å resolution. The structure adopts a typical (β/α)(8)-barrel fold with an additional N-terminal extension of 46 residues. A detailed comparison of the crystal structure of TtIGPS with available structures of IGPS from the archaeon Sulfolobus solfataricus (SsIGPS) and the bacteria Thermotoga maritima (TmIGPS) and Escherichia coli (EcIGPS) has been performed. Although the overall folds of the proteins are the same, there are differences in amino-acid composition, structural rigidity, ionic features and stability clusters which may account for the high thermostability of the hyperthermophilic (SsIGPS and TmIGPS) and thermophilic (TtIGPS) proteins when compared with the mesophilic EcIGPS. The thermostability of IGPS seems to be established mainly by favourable interactions of charged residues, salt bridges and the spatial distribution of relatively rigid clusters of extensively interacting residues.

  19. Acute on chronic liver failure in a patient with sickle cell anaemia (HbSS).

    PubMed

    Im, Dana DaEun; Essien, Utibe; DePasse, Jacqueline W; Chiappa, Victor

    2015-07-01

    A man in his late 40s with sickle cell anaemia (HbSS) presented to the emergency department with 2 weeks of diffuse oedema, increased abdominal girth and dyspnoea. His anasarca was thought to be indicative of an acute decompensation of his known liver cirrhosis with transfusion-induced haemosiderosis. While his anasarca improved with diuresis, his direct hyperbilirubinaemia suddenly worsened without any signs of haemolysis, biliary disease or obstruction. He also developed an acute worsening in serum creatinine (1.17-7.0 mg/dL in 7 days) despite subsequent treatment for presumed hepatorenal syndrome (HRS). Given his clinical decline, the patient's goals of care were transitioned to comfort measures only. His clinical presentation and rapid liver and renal deterioration were most typical of sickle cell intrahepatic cholestasis (SCIC). SCIC can lead to rapid deterioration in renal function and can be mistaken for HRS. When SCIC is suspected, consideration of exchange transfusions should be made early.

  20. Lipid fluidity at different regions in LDL and HDL of {beta}-thalassemia/Hb E patients

    SciTech Connect

    Morales, Noppawan Phumala . E-mail: scnpm@mahidol.ac.th; Charlermchoung, Chalermkhwan; Luechapudiporn, Rataya; Yamanont, Paveena; Fucharoen, Suthat; Chantharaksri, Udom

    2006-11-24

    Atherosclerosis-related vascular complications in {beta}-thalassemia/hemoglobin E ({beta}-thal/Hb E) patients may result from iron induced oxidation of lipoproteins. To identify the specific site of oxidative damage, changes in lipid fluidity at different regions in LDL and HDL particle were investigated using two fluorescence probes and two ESR spin probes. The magnitude of increased lipid fluidity in thalassemic lipoproteins was dependent on the location of the probes. In hydrophobic region, the rotational correlation times for 16-doxyl stearic acid and DPH anisotropy were markedly changed in LDL and HDL of the patients. In the surface region, there was only a slight change in the order parameter (S) for 5-doxyl stearic acid and TMA-DPH anisotropy. Lipid fluidity at the core of LDL and HDL showed good correlation with oxidative stress markers, the ratio of CL/CO, and the level of {alpha}-tocopherol, suggesting that hydrophobic region of thalassemic lipoprotein was a target site for oxidative damage.

  1. The HB-2D Polarized Neutron Development Beamline at the High Flux Isotope Reactor

    NASA Astrophysics Data System (ADS)

    Crow, Lowell; Hamilton, WA; Zhao, JK; Robertson, JL

    2016-09-01

    The Polarized Neutron Development beamline, recently commissioned at the HB-2D position on the High Flux Isotope Reactor (HFIR) at Oak Ridge National Laboratory, provides a tool for development and testing of polarizers, polarized neutron devices, and prototyping of polarized neutron techniques. With available monochromators including pyrolytic graphite and polarizing enriched Fe-57 (Si), the instrument has operated at 4.25 and 2.6 Å wavelengths, using crystal, supermirror, or He-3 polarizers and analyzers in various configurations. The Neutron Optics and Development Team has used the beamline for testing of He-3 polarizers for use at other HFIR and Spallation Neutron Source (SNS) instruments, as well as a variety of flipper devices. Recently, we have acquired new supermirror polarizers which have improved the instrument performance. The team and collaborators also have continuing demonstration experiments of spin-echo focusing techniques, and plans to conduct polarized diffraction measurements. The beamline is also used to support a growing use of polarization techniques at present and future instruments at SNS and HFIR.

  2. Occult HBV infection in anti-HBs-positive young adults after neonatal HB vaccination.

    PubMed

    Xu, Libin; Wei, Yong; Chen, Taoyang; Lu, Jianhua; Zhu, Chang-Lin; Ni, Zhengping; Huang, Fei; Du, Jun; Sun, Zongtang; Qu, Chunfeng

    2010-08-23

    Previous follow-up on our neonatal HB vaccination cohorts with 80,000 individuals in Qidong, China, showed significant protective efficacy of immunization against HBV infection in childhood. However, some vaccinees were found to be HBsAg negative, but anti-HBs positive and anti-HBc positive at age 10-11 years. To study this phenomenon, 2919 vaccinees at age 19-21 years were sampled from the cohort. HBsAg(-), anti-HBs(+) and anti-HBc(+) were found in 124/2919 (4.2%) of the vaccinees. HBV DNA was detectable in 81/106 sample sera by using nested PCR. The PreS-S regions of HBV were sequenced in 41 randomly sampled sera. All the HBV isolates were HBV genotype C. Twenty one isolates (21/41, 51.2%) were identical to an HBV isolated in this area (GU434374). Only 4/41 (9.8%) showed mutations at the "a" epitope and three of them were G145A. The other mutations were found outside of the "a" epitope. Most of the sera contained <10,000 HBV copies/ml. Occult HBV infection happened in the young adults with HBsAg(-), anti-HBs(+) and anti-HBc(+) status, who received neonatal vaccination in Qidong.

  3. Crystal structure of novel NADP-dependent 3-hydroxyisobutyrate dehydrogenase from Thermus thermophilus HB8.

    PubMed

    Lokanath, Neratur K; Ohshima, Noriyasu; Takio, Koji; Shiromizu, Ikuya; Kuroishi, Chizu; Okazaki, Nobuo; Kuramitsu, Seiki; Yokoyama, Shigeyuki; Miyano, Masashi; Kunishima, Naoki

    2005-09-30

    3-Hydroxyisobutyrate, a central metabolite in the valine catabolic pathway, is reversibly oxidized to methylmalonate semialdehyde by a specific dehydrogenase belonging to the 3-hydroxyacid dehydrogenase family. To gain insight into the function of this enzyme at the atomic level, we have determined the first crystal structures of the 3-hydroxyisobutyrate dehydrogenase from Thermus thermophilus HB8: holo enzyme and sulfate ion complex. The crystal structures reveal a unique tetrameric oligomerization and a bound cofactor NADP+. This bacterial enzyme may adopt a novel cofactor-dependence on NADP, whereas NAD is preferred in eukaryotic enzymes. The protomer folds into two distinct domains with open/closed interdomain conformations. The cofactor NADP+ with syn nicotinamide and the sulfate ion are bound to distinct sites located at the interdomain cleft of the protomer through an induced-fit domain closure upon cofactor binding. From the structural comparison with the crystal structure of 6-phosphogluconate dehydrogenase, another member of the 3-hydroxyacid dehydrogenase family, it is suggested that the observed sulfate ion and the substrate 3-hydroxyisobutyrate share the same binding pocket. The observed oligomeric state might be important for the catalytic function through forming the active site involving two adjacent subunits, which seems to be conserved in the 3-hydroxyacid dehydrogenases. A kinetic study confirms that this enzyme has strict substrate specificity for 3-hydroxyisobutyrate and serine, but it cannot distinguish the chirality of the substrates. Lys165 is likely the catalytic residue of the enzyme.

  4. Modelling the Relative Contribution of Fasting and Post-Prandial Plasma Glucose to HbA1c in Healthy and Type 2 Diabetic Subjects

    ERIC Educational Resources Information Center

    Ollerton, Richard L.; Luzio, Steven D.; Owens, David R.

    2004-01-01

    Glycated haemoglobin (HbA1c) is regarded as the gold standard of glucose homeostasis assessment in diabetes. There has been much discussion in recent medical literature of experimental results concerning the relative contribution of fasting and post-prandial glucose levels to the value of HbA1c. A mathematical model of haemoglobin glycation is…

  5. Ethylene stimulation of latex yield depends on the expression of a sucrose transporter (HbSUT1B) in rubber tree (Hevea brasiliensis).

    PubMed

    Dusotoit-Coucaud, Anaïs; Kongsawadworakul, Panida; Maurousset, Laurence; Viboonjun, Unshira; Brunel, Nicole; Pujade-Renaud, Valérie; Chrestin, Hervé; Sakr, Soulaïman

    2010-12-01

    Hevea brasiliensis is an important industrial crop for natural rubber production. Latex biosynthesis occurs in the cytoplasm of highly specialized latex cells and requires sucrose as the unique precursor. Ethylene stimulation of latex production results in high sugar flow from the surrounding cells of inner bark towards the latex cells. The aim of this work was to understand the role of seven sucrose transporters (HbSUTs) and one hexose transporter (HbHXT1) in this process. Two Hevea clones were used: PB217 and PB260, respectively described as high and low yielding clones. The expression pattern of these sugar transporters (HbSUTs and HbHXT1) was monitored under different physiological conditions and found to be maximal in latex cells. HbSUT1, one of the most abundant isoforms, displayed the greatest response to ethylene treatment. In clone PB217, ethylene treatment led to a higher accumulation of HbSUT1B in latex cells than in the inner bark tissues. Conversely, stronger expression of HbSUT1B was observed in inner bark tissues than in latex cells of PB260. A positive correlation with HbSUT1B transcript accumulation and increased latex production was further supported by its lower expression in latex cells of the virgin clone PB217.

  6. HbA(1c) diagnostic categories and beta-cell function relative to insulin sensitivity in overweight/obese adolescents

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The recommended HbA1c diagnostic categories remain controversial and their utility in doubt in pediatrics. We hypothesized that alterations in the pathophysiologic mechanisms of type 2 diabetes may be evident in the American Diabetes Association recommended at-risk/prediabetes category (HbA(1c) 5.7 ...

  7. HbCIPK2, a novel CBL-interacting protein kinase from halophyte Hordeum brevisubulatum, confers salt and osmotic stress tolerance.

    PubMed

    Li, Ruifen; Zhang, Junwen; Wu, Guangyu; Wang, Hongzhi; Chen, Yajuan; Wei, Jianhua

    2012-09-01

    Protein kinases play an important role in regulating the response to abiotic stress in plant. CIPKs are plant-specific signal transducers, and some members have been identified. However, the precise functions of novel CIPKs still remain unknown. Here we report that HbCIPK2 is a positive regulator of salt and osmotic stress tolerance. HbCIPK2 was screened out of the differentially expressed fragments from halophyte Hordeum brevisubulatum by cDNA-AFLP technique, and was a single-copy gene without intron. Expression of HbCIPK2 was increased by salt, drought and ABA treatment. HbCIPK2 is mainly localized to the plasma membrane and nucleus. Ectopic expression of 35S:HbCIPK2 not only rescued the salt hypersensitivity in Arabidopsis mutant sos2-1, but also enhanced salt tolerance in Arabidopsis wild type, and exhibited tolerance to osmotic stress during germination. The HbCIPK2 contributed to the ability to prevent K(+) loss in root and to accumulate less Na(+) in shoot resulting in K(+) /Na(+) homeostasis and protection of root cell from death, which is consistent with the gene expression profile of HbCIPK2-overexpressing lines. These findings imply possible novel HbCIPK2-mediated salt signalling pathways or networks in H. brevisubulatum.

  8. Identification of a rare variant haemoglobin (Hb Sinai-Baltimore) causing spuriously low haemoglobin A(1c) values on ion exchange chromatography.

    PubMed

    Smith, Geoff; Murray, Heather; Brennan, Stephen O

    2013-01-01

    Commonly used methods for assay of haemoglobin A(1c) (HbA(1c)) are susceptible to interference from the presence of haemoglobin variants. In many systems, the common variants can be identified but scientists and pathologists must remain vigilant for more subtle variants that may result in spuriously high or low HbA(1c) values. It is clearly important to recognize these events whether HbA(1c) is being used as a monitoring tool or, as is increasingly the case, for diagnostic purposes. We report a patient with a rare haemoglobin variant (Hb Sinai-Baltimore) that resulted in spuriously low values of HbA(1c) when assayed using ion exchange chromatography, and the steps taken to elucidate the nature of the variant.

  9. Genetic Variants at BCL11A and HBS1L-MYB loci Influence Hb F Levels in Chinese Zhuang β-Thalassemia Intermedia Patients.

    PubMed

    Lai, Yunli; Chen, Yun; Chen, Biyan; Zheng, Haiyang; Yi, Sheng; Li, Guojian; Wei, Hongwei; He, Sheng; Zheng, Chenguang

    2016-11-01

    Increased Hb F levels can ameliorate the symptoms of β-thalassemia (β-thal). Due to the genetic heterogenicity of β-thal, the relationship between genetic variants in modifier genes and Hb F level has been studied in different populations. The Chinese Zhuang has the second largest population in China and has 6.78% prevalence of β-thal. However, the effects of these single nucleotide polymorphism (SNP) variants on the Hb F levels of β-thal intermedia (β-TI) patients in this population have not been reported. To explore the association between modifier loci (β-globin gene cluster, HBS1L-MYB intergenic region and BCL11A) and Hb F levels in Chinese Zhuang β-TI patients, 96 unrelated β-TI patients (50 males and 46 females) with different Hb F levels were recruited and genotyped by mass spectrometry. A total of 13 SNPs were confirmed to be in a significant relationship with Hb F levels in this population. Of these, high-risk genotypes of six Hb F-associated SNPs, rs9376090, rs7776054, rs9399137, rs9389268, rs9402685 in the HBS1L-MYB intergenic region and rs189984760 in the BCL11A locus, showed association with high Hb F levels, especially for SNPs in linkage disequilibrium. One novel Hb F-associated SNP, rs189984760, was identified in our study. Our findings will be of valuable reference for correlation between modifier genes and Hb F in Chinese Zhuang populations and may lead to better understand the modifying mechanisms for β-thal.

  10. Side-necked turtle (Pleurodira, Chelonia, reptilia) hemoglobin: cDNA-derived primary structures and X-ray crystal structures of Hb A.

    PubMed

    Hasegawa, Tomokazu; Shishikura, Fumio; Kuwada, Takao

    2011-03-01

    Red blood cells of yellow-spotted river turtles (Podocnemis unifilis, Pleurodira, Chelonia, REPTILIA) have two hemoglobin (Hb) components, Hb A and Hb D. We purified the hemoglobin component homologous to amniote (reptiles, birds, and mammals) adult Hb A which comprises two identical α(A) -globin polypeptides and two identical β-globin polypeptides. To establish the crystal structure of Podocnemis Hb A, we first determined the globin primary structures using cDNA nucleotide sequencing with the assistance of protein sequencing. The purified Podocnemis Hb A produced a different form of crystal for each of the two different buffer systems used: form A, tetragonal crystals (space group, P4₁2₁2), produced under neutral pH (pH 7-8) conditions; and form B, hexagonal crystals (space group, P6₁22), produced under high alkaline pH (pH 11-13) conditions. Single crystals of the two forms were examined by Raman microscopy with an excitation of 532 nm, indicating their structural differences. The crystal structures of the two forms were constructed by X-ray crystallographic diffraction at a resolution of 2.20 Å for form A and 2.35 Å for form B. The differences of the tertiary and quaternary structures of the two forms were marginal; however, one clear difference was found in helix structure. When comparing Podocnemis Hb A with Hb A from specimens in other taxa, such as Anser indicus (birds) and Homo sapiens (mammals) by SHELXPRO, the root mean square deviation (RMSD) between the corresponding Cα atoms of the two globins does not exceed 2.0 Å. These low values indicate the crystal structures resemble each other. Our data on X-ray crystal structures and Raman spectra not only reveal the first findings on the two crystal forms of Podocnemis unifilis Hb A but also provide the first refined models for reptilian adult Hb A.

  11. Fire-LCA study of TV sets with V0 and HB enclosure material.

    PubMed

    Simonson, Margaret; Tullin, Claes; Stripple, Håkan

    2002-02-01

    A novel Life-Cycle Assessment model (Fire-LCA) has been defined for the determination of the environmental impact of measures taken to attain a high level of fire safety. This study, which represents the first application of this LCA model, concentrates on a comparison between a TV with an enclosure manufactured with a flame retardant (FR) plastic (V0-rated high impact polystyrene, HIPS, typical for the US market) and one manufactured with a non-flame retardant (HB-rated HIPS, typical for the European market). A fire model has been defined based on international statistics, which indicate that use of V0 rated enclosure material essentially removes the risk of TV fires while approximately 165 TV fires occur per million TVs in Europe each year where the enclosure material is breached. The application of the model indicates that emissions of some key species (such as dibenzodioxins and PAH) are actually lower for the TV with the FR enclosure than for the TV with the NFR enclosure. This has direct reprercussions for the assessment of the environmental impact of the FR TV relative to that of the NFR TV. Finally, when considering the risk associated with the use of flame retardants, it is also important to consider the risk associated with fires. Based on the in-depth analysis of available fire statistics, conducted as a part of this study, it has been estimated that as many as 160 people may die each year in Europe as a direct result of TV fires and as many as 2000 may be injured in the same period.

  12. A novel arsenate reductase from the bacterium Thermus thermophilus HB27: its role in arsenic detoxification.

    PubMed

    Del Giudice, Immacolata; Limauro, Danila; Pedone, Emilia; Bartolucci, Simonetta; Fiorentino, Gabriella

    2013-10-01

    Microorganisms living in arsenic-rich geothermal environments act on arsenic with different biochemical strategies, but the molecular mechanisms responsible for the resistance to the harmful effects of the metalloid have only partially been examined. In this study, we investigated the mechanisms of arsenic resistance in the thermophilic bacterium Thermus thermophilus HB27. This strain, originally isolated from a Japanese hot spring, exhibited tolerance to concentrations of arsenate and arsenite up to 20mM and 15mM, respectively; it owns in its genome a putative chromosomal arsenate reductase (TtarsC) gene encoding a protein homologous to the one well characterized from the plasmid pI258 of the Gram+bacterium Staphylococcus aureus. Differently from the majority of microorganisms, TtarsC is part of an operon including genes not related to arsenic resistance; qRT-PCR showed that its expression was four-fold increased when arsenate was added to the growth medium. The gene cloning and expression in Escherichia coli, followed by purification of the recombinant protein, proved that TtArsC was indeed a thioredoxin-coupled arsenate reductase with a kcat/KM value of 1.2×10(4)M(-1)s(-1). It also exhibited weak phosphatase activity with a kcat/KM value of 2.7×10(-4)M(-1)s(-1). The catalytic role of the first cysteine (Cys7) was ascertained by site-directed mutagenesis. These results identify TtArsC as an important component in the arsenic resistance in T. thermophilus giving the first structural-functional characterization of a thermophilic arsenate reductase.

  13. Falsely increased HbA1c values by HPLC and falsely decreased values by immunoassay lead to identification of Hb Okayama and help in the management of a diabetic patient.

    PubMed

    Frers, C R; Dorn, S; Schmidt, W; Kochhan, L; Simon-Schultz, J; Arndt, R

    2000-01-01

    A falsely increased HbA1c value of 47.1% was determined by cation exchange chromatography during a routine HbA1c measurement of the blood sample from a 63-year-old diabetic male patient living in Hamburg, Germany. In former determinations by immunological assays falsely decreased values in the range of 5.0 to 5.5% were obtained. The sample was inconspicuous in alkaline hemoglobin electrophoresis. But acid hemoglobin electrophoresis confirmed the falsely increased value. These facts let us consider the existence of a heterozygous "silent hemoglobin variant", such as hemoglobin Okayama, with an amino acid substitution in one of the first four amino acids of the beta chain, representing the epitope of common immunoassays. DNA analyses confirmed this presumption and we found the heterozygous mutation hemoglobin Okayama [beta 2 (NA 2) His (CAC)-->Gln (CAA)]. Knowing that an immunological assay only detects about half of the present HbA1c, the obtained values can be used for therapeutic management of this diabetic patient.

  14. Sickle cell anemia and α-thalassemia: a modulating factor in homozygous HbS/S patients in Oman.

    PubMed

    Hassan, S M; Al Muslahi, M; Al Riyami, M; Bakker, E; Harteveld, C L; Giordano, P C

    2014-01-01

    We report the general phenotype severity and the hematological presentation in a cohort of 125 sickle cell anemia (SCA) patients with identical homozygous HbS/S genotype and categorized by identical β(S) haplotype, both with and without alpha thalassemia. No clear general phenotype correlation was found when patients were compared regardless of the haplotype but overall, patients with homozygous alpha thalassemia (α-/α-) had the highest Hb, HCT, RBC and the lowest MCV, MCH and MCHC levels. When patients with identical haplotype were compared, the mildest hematological and clinical conditions were observed in patients of the Asian/Asian haplotype, also known as Arab-Indian haplotype, and carriers of α-thalassemia, suggesting an additional ameliorating effect of alpha thalassemia. In conclusion, our results show that alpha thalassemia improves the hematological conditions but amelioration of the general disease severity is only noticed when compared in cohorts of the same haplotype.

  15. Expression, crystallization and preliminary X-ray analysis of an outer membrane protein from Thermus thermophilus HB27

    PubMed Central

    Brosig, Alexander; Nesper, Jutta; Welte, Wolfram; Diederichs, Kay

    2008-01-01

    The cell envelope of the thermophilic bacterium Thermus thermophilus is multilayered and includes an outer membrane with integral outer membrane proteins that are not well characterized. The hypothetical protein TTC0834 from T. thermophilus HB27 was identified as a 22 kDa outer membrane protein containing eight predicted β-strands. TTC0834 was expressed with an N-­terminal His tag in T. thermophilus HB8 and detected in the S-layer/outer membrane envelope fraction. His-TTC0834 was purified and crystallized under various conditions. Native data sets were collected to 3.2 Å resolution and the best diffracting crystals belonged to space group P3121 or P3221, with unit-cell parameters a = b = 166.67, c = 97.53 Å. PMID:18540069

  16. Expression, crystallization and preliminary X-ray analysis of an outer membrane protein from Thermus thermophilus HB27.

    PubMed

    Brosig, Alexander; Nesper, Jutta; Welte, Wolfram; Diederichs, Kay

    2008-06-01

    The cell envelope of the thermophilic bacterium Thermus thermophilus is multilayered and includes an outer membrane with integral outer membrane proteins that are not well characterized. The hypothetical protein TTC0834 from T. thermophilus HB27 was identified as a 22 kDa outer membrane protein containing eight predicted beta-strands. TTC0834 was expressed with an N-terminal His tag in T. thermophilus HB8 and detected in the S-layer/outer membrane envelope fraction. His-TTC0834 was purified and crystallized under various conditions. Native data sets were collected to 3.2 A resolution and the best diffracting crystals belonged to space group P3(1)21 or P3(2)21, with unit-cell parameters a = b = 166.67, c = 97.53 A.

  17. Characterization of carbon nanotube (MWCNT) containing P(3HB)/bioactive glass composites for tissue engineering applications.

    PubMed

    Misra, Superb K; Ohashi, F; Valappil, Sabeel P; Knowles, Jonathan C; Roy, I; Silva, S Ravi P; Salih, Vehid; Boccaccini, Aldo R

    2010-03-01

    Poly(3-hydroxybutyrate) (P(3HB)) composites with bioactive glass particles and multiwall carbon nanotubes (MWCNTs) were prepared and used to identify whether the electrical properties of MWCNTs can be used to detect the bioactivity of P(3HB)/bioactive glass composites. The presence of MWCNTs (2-7 wt.%) increased the surface roughness of the composites. The presence of MWCNTs in low quantity enhanced MG-63 osteoblast-like cell attachment and proliferation compared to composites with higher concentration of MWCNTs. Current-voltage measurements demonstrated that the electrical resistance of the composites containing bioactive glass particles decreased over a 45-day immersion period in SBF, whereas composites without bioactive glass showed no significant change over the same period.

  18. No identifiable Hb1Ac or lifestyle change after a comprehensive diabetes programme including motivational interviewing: A cluster randomised trial

    PubMed Central

    2013-01-01

    Abstract Objective To study the effectiveness of a comprehensive diabetes programme in general practice that integrates patient-centred lifestyle counselling into structured diabetes care. Design and setting Cluster randomised trial in general practices. Intervention Nurse-led structured diabetes care with a protocol, record keeping, reminders, and feedback, plus training in motivational interviewing and agenda setting. Subjects Primary care nurses in 58 general practices and their 940 type 2 diabetes patients with an HbA1c concentration above 7%, and a body mass index (BMI) above 25 kg/m2. Main outcome measures HbA1c, diet, and physical activity (medical records and patient questionnaires). Results Multilevel linear and logistic regression analyses adjusted for baseline outcomes showed that despite active nurse participation in the intervention, the comprehensive programme was no more effective than usual care after 14 months, as shown by HbA1c levels (difference between groups = 0.13; CI 20.8–0.35) and diet (fat (difference between groups = 0.19; CI 20.82–1.21); vegetables (difference between groups = 0.10; CI-0.21–0.41); fruit (difference between groups = 20.02; CI 20.26–0.22)), and physical activity (difference between groups = 21.15; CI 212.26–9.97), or any of the other measures of clinical parameters, patient's readiness to change, or quality of life. Conclusion A comprehensive programme that integrated lifestyle counselling based on motivational interviewing principles integrated into structured diabetes care did not alter HbA1c or the lifestyle related to diet and physical activity. We thus question the impact of motivational interviewing in terms of its ability to improve routine diabetes care in general practice. PMID:23659710

  19. Comparison of nanoscale and microscale bioactive glass on the properties of P(3HB)/Bioglass composites.

    PubMed

    Misra, Superb K; Mohn, Dirk; Brunner, Tobias J; Stark, Wendelin J; Philip, Sheryl E; Roy, Ipsita; Salih, Vehid; Knowles, Jonathan C; Boccaccini, Aldo R

    2008-04-01

    This study compares the effects of introducing micro (m-BG) and nanoscale (n-BG) bioactive glass particles on the various properties (thermal, mechanical and microstructural) of poly(3hydroxybutyrate) (P(3HB))/bioactive glass composite systems. P(3HB)/bioactive glass composite films with three different concentrations of m-BG and n-BG (10, 20 and 30 wt%, respectively) were prepared by a solvent casting technique. The addition of n-BG particles had a significant stiffening effect on the composites, modulus when compared with m-BG. However, there were no significant differences in the thermal properties of the composites due to the addition of n-BG and m-BG particles. The systematic addition of n-BG particles induced a nanostructured topography on the surface of the composites, which was not visible by SEM in m-BG composites. This surface effect induced by n-BG particles considerably improved the total protein adsorption on the n-BG composites compared to the unfilled polymer and the m-BG composites. A short term in vitro degradation (30 days) study in simulated body fluid (SBF) showed a high level of bioactivity as well as higher water absorption for the P(3HB)/n-BG composites. Furthermore, a cell proliferation study using MG-63 cells demonstrated the good biocompatibility of both types of P(3HB)/bioactive glass composite systems. The results of this investigation confirm that the addition of nanosized bioactive glass particles had a more significant effect on the mechanical and structural properties of a composite system in comparison with microparticles, as well as enhancing protein adsorption, two desirable effects for the application of the composites in tissue engineering.

  20. HB Hillingdon [alpha46(CE4)Phe-->Val (alpha1 Or alpha2)]: a new alpha chain hemoglobin variant.

    PubMed

    Babb, Anna; Solaiman, Susannah; Green, Brian N; Mantio, Debbie; Patel, Ketan

    2009-01-01

    Routine antenatal hemoglobinopathy screening detected a new alpha chain variant that eluted with Hb A(2) on cation exchange high performance liquid chromatography (HPLC) in a lady of Sri Lankan origin who had normal hematological indices. The mutation was identified by electrospray ionization mass spectrometry (ESI-MS) as alpha46(CE4)Phe-->Val, inferring that the variant was due to a single base change at codon 46 (TTC>GTC) of the alpha1- or alpha2-globin genes.

  1. Development of plasmid cloning vectors for Thermus thermophilus HB8: Expression of a heterologous, plasmid-borne kanamycin nucleotidyltransferase gene

    SciTech Connect

    Mather, M.W.; Fee, J.A. )

    1992-01-01

    While several thermus genes have been cloned and T. thermophilus has been shown to be transformable, molecular genetic studies of these thermophiles have been hampered by the absence of selectable cloning vectors. The authors have constructed a selectable plasmid by random insertion of a heterologous gene encoding a thermostable kanamycin nucleotidyltransferase activity into a cryptic, multicopy plasmid from T. thermophilus HB8. This plasmid should serve as a suitable starting point for the development of a gene expression system for T. thermophilus.

  2. Radiolytic hydrogen production from process vessels in HB line - production rates compared to evolution rates and discussion of LASL reviews

    SciTech Connect

    Bibler, N.E.

    1992-11-12

    Hydrogen production from radiolysis of aqueous solutions can create a safety hazard since hydrogen is flammable. At times this production can be significant, especially in HB line where nitric acid solutions containing high concentrations of Pu-238, an intense alpha emitter, are processed. The hydrogen production rates from these solutions are necessary for safety analyses of these process systems. The methods and conclusions of hydrogen production rate tests are provided in this report.

  3. A Mouse Model of Otitis Media Identifies HB-EGF as a Mediator of Inflammation-Induced Mucosal Proliferation

    PubMed Central

    Pak, Kwang; Chavez, Eduardo; Kurabi, Arwa; Baird, Andrew; Wasserman, Stephen I.; Ryan, Allen F.

    2014-01-01

    Objective Otitis media is one of the most common pediatric infections. While it is usually treated without difficulty, up to 20% of children may progress to long-term complications that include hearing loss, impaired speech and language development, academic underachievement, and irreversible disease. Hyperplasia of middle ear mucosa contributes to the sequelae of acute otitis media and is of important clinical significance. Understanding the role of growth factors in the mediation of mucosal hyperplasia could lead to the development of new therapeutic interventions for this disease and its sequelae. Methods From a whole genome gene array analysis of mRNA expression during acute otitis media, we identified growth factors with expression kinetics temporally related to hyperplasia. We then tested these factors for their ability to stimulate mucosal epithelial growth in vitro, and determined protein levels and histological distribution in vivo for active factors. Results From the gene array, we identified seven candidate growth factors with upregulation of mRNA expression kinetics related to mucosal hyperplasia. Of the seven, only HB-EGF (heparin-binding-epidermal growth factor) induced significant mucosal epithelial hyperplasia in vitro. Subsequent quantification of HB-EGF protein expression in vivo via Western blot analysis confirmed that the protein is highly expressed from 6 hours to 24 hours after bacterial inoculation, while immunohistochemistry revealed production by middle ear epithelial cells and infiltrating lymphocytes. Conclusion Our data suggest an active role for HB-EGF in the hyperplasia of the middle ear mucosal epithelium during otitis media. These results imply that therapies targeting HB-EGF could ameliorate mucosal growth during otitis media, and thereby reduce detrimental sequelae of this childhood disease. PMID:25033458

  4. A novel hemoglobin variant found on the α1 chain: Hb KSVGH (HBA1: p.Lys57_Gly58insSerHisGlySerAlaGlnValLys).

    PubMed

    Wang, Mei-Chun; Tsai, Kuo-Wang; Chu, Chih-Hsun; Yu, Ming-Sun; Lam, Hing-Chung

    2015-01-01

    Glycosylated hemoglobin (Hb A1C) is a crucial indicator for the long-term control and the diagnosis of diabetes. However, the presence of hemoglobin (Hb) variants may affect the measured value of Hb A1C and result in an abnormal graph trend and inconsistency between the clinical blood sugar test and Hb A1C values. In this study, laboratory data of 41,267 patients with diabetes were collected. The Hb A1C levels and the graph results were examined. We identified 74 cases containing abnormal Hb A1C graph trends. The conducted blood cell counts and capillary Hb electrophoresis were used to analyze Hb variants. We also determined gene variation for the Hb variants by a sequence approach. Fifteen different types of Hb variants were identified in this study. Among these, we found a novel variant in which the α1 subunit of Hb showed an insertion of 24 nucleotides (nts) between the 56th and 57th residues. We named this novel variant Hb Kaohsiung Veterans General Hospital (Hb KSVGH) (HBA1: p.Lys57_Gly58insSerHisGlySerAlaGlnValLys).

  5. UNC-4 represses CEH-12/HB9 to specify synaptic inputs to VA motor neurons in C. elegans.

    PubMed

    Von Stetina, Stephen E; Fox, Rebecca M; Watkins, Kathie L; Starich, Todd A; Shaw, Jocelyn E; Miller, David M

    2007-02-01

    In Caenorhabditis elegans, VA and VB motor neurons arise as lineal sisters but synapse with different interneurons to regulate locomotion. VA-specific inputs are defined by the UNC-4 homeoprotein and its transcriptional corepressor, UNC-37/Groucho, which function in the VAs to block the creation of chemical synapses and gap junctions with interneurons normally reserved for VBs. To reveal downstream genes that control this choice, we have employed a cell-specific microarray strategy that has now identified unc-4-regulated transcripts. One of these genes, ceh-12, a member of the HB9 family of homeoproteins, is normally restricted to VBs. We show that expression of CEH-12/HB9 in VA motor neurons in unc-4 mutants imposes VB-type inputs. Thus, this work reveals a developmental switch in which motor neuron input is defined by differential expression of transcription factors that select alternative presynaptic partners. The conservation of UNC-4, HB9, and Groucho expression in the vertebrate motor circuit argues that similar mechanisms may regulate synaptic specificity in the spinal cord.

  6. Implementation of the HbA1c IFCC unit --from the laboratory to the consumer: The New Zealand experience.

    PubMed

    Florkowski, Christopher; Crooke, Michael; Reed, Maxine

    2014-05-15

    In 2007, an international consensus statement recommended that HbA1c results should be reported world-wide in IFCC units (mmol/mol) and also the more familiar derived percentage units using a master equation. In New Zealand, the HbA1c IFCC units have been successfully implemented and used exclusively since 3rd October 2011 (following a 2 year period of reporting both units) for both patient monitoring and the diagnosis of diabetes, with a diagnostic cut-off of ≥50 mmol/mol. The consultation process in New Zealand dates back to 2003, well before the international recommendations were made. It reflects the close cooperation between the clinical and laboratory communities in New Zealand, particularly through the agency of the New Zealand Society for the Study of Diabetes (NZSSD), a key organisation in New Zealand open to all those involved in the care of people with diabetes and the national advisory body on scientific and clinical diabetes care and standards. There was a phased process of consultation designed to increase familiarity and comfort with the new units and the final step was coupled with the adoption of HbA1c as a diagnostic test with some evidence-based pragmatism around using the rounded cut-off. Genuine clinical engagement is vital in such a process.

  7. Bio-plastic (P-3HB-co-3HV) from Bacillus circulans (MTCC 8167) and its biodegradation.

    PubMed

    Phukon, Pinkee; Saikia, Jyoti Prasad; Konwar, Bolin Kumar

    2012-04-01

    Polyhydroxyalkanoates (PHAs) are naturally occurring polyesters synthesized by bacteria for carbon and energy storage and it has commercial potential as bioplastic. The bacterial species Bacillus circulans MTCC 8167, isolated from crude oil contaminated soil, can efficiently produce medium chain length polyhydroxyalkanoates (P-3HB-co-3HV) from cheap carbon sources like dextrose. The molecular mass of P-3HB-co-3HV was reported as 5.1×10(4)Da with polydispersity index of 1.21 by gel permeation chromatography. In the present investigation different bacteria and fungi species were used for testing the biodegradability of the extracted polymer. The FTIR spectra of the biodegraded PHBV film showed a decrease in the peak from 1735 cm(-1) (untreated film) to 1675 cm(-1), and disappearance of a peak present in the control at 2922 cm(-1) indicating the breakdown of ester (>C=O) or O-R group and -C=H bond, respectively. From biodegradability testing, the tested microorganisms were found to have decisive contribution to the biodegradation of P-3HB-co-3HV polymer.

  8. DTPw-HB and Hib primary and booster vaccination: combined versus separate administration to Latin American children.

    PubMed

    Santos, José Ignacio; Martin, Amando; De Leon, Tirza; Rivera, Luis; Gaitán, Maria Elisa García; Del Rio, Carlos; Oselka, Gabriel; Cervantes, Yolanda; Rubio, Pilar; Clemens, Sue Ann Costa; de Mendonça, João Silva

    2002-03-15

    This multicentre study was designed to establish the reactogenicity and immunogenicity profiles of primary and booster vaccination with diphtheria, tetanus, and pertussis whole-cell-hepatitis B/Haemophilus influenzae type-b (DTPw-HB/Hib) administered as either a syringe mix or as separate injections in 400 Latin American children. Both vaccine regimens were equally well tolerated and elicited post-primary excellent seropositivity rates at or close to 100% for all five component antigens. With regard to HB, 100% of subjects in the combined vaccination group, and 98.8% subjects in the separate injection vaccination group reached seroprotective antibody concentrations (>or=10 mIU/ml) 1 month after the primary vaccination course. Equally high anti-PRP antibody concentrations were reached 1 month after vaccination, with 100% of seroprotected subjects in the combined vaccination group (antibody concentrations >or=0.15 microg/ml), against 99.4% in the separate injection vaccination group. Seroprotective anti-HBs and anti-PRP antibody concentration levels persisted approximately 1 year after the primary vaccination course, just prior to booster vaccination. Finally, a significant increase of all antibody concentrations could be observed after the booster vaccination, since all but one subject in the separate injection vaccination group had protective levels of anti-HBs and anti-PRP antibodies 1 month after the booster dose. These results suggest that the combination of DTPw-HB and Hib vaccines provides an effective means for increasing vaccine coverage in childhood vaccination programmes.

  9. Beta-globin gene cluster haplotypes and HbF levels are not the only modulators of sickle cell disease in Lebanon.

    PubMed

    Inati, A; Taher, A; Bou Alawi, W; Koussa, S; Kaspar, H; Shbaklo, H; Zalloua, P A

    2003-02-01

    Sickle cell disease (SCD) is an inherited autosomal recessive disorder of the beta-globin chain. Despite the fact that all subjects with SCD have the same single base pair mutation, the severity of the clinical and hematological manifestations is extremely variable. This study examined for the first time in Lebanon the correlation between the clinical manifestation of SCD and the beta-globin gene haplotypes. The haplotypes of 50 patients diagnosed with SCD were determined using polymerase chain reaction amplification of fragments containing nine polymorphic restriction sites around and within the epsilon-Ggamma-Agamma-psibeta-delta-beta-globin gene complex. Most reported haplotypes were found in our population with the Benin haplotype as the most prevalent one. When the patients were divided according to their HbF levels into three groups (Group A: HbF < 5%, Group B: HbF between 5 and 15%, and Group C: HbF > 15%), surprisingly, the highest levels of HbF were associated with the most severe clinical cases. Our findings suggest that fetal hemoglobin levels are important but not the only parameters that affect the severity of the disease. In addition, the high levels of HbF in patients with CAR haplotypes did not seem to ameliorate the severity of symptoms, suggesting that genetic factors other than haplotypes are the major determinants of increased HbF levels in Lebanon.

  10. The sunflower transcription factor HaHB11 confers tolerance to water deficit and salinity to transgenic Arabidopsis and alfalfa plants.

    PubMed

    Cabello, Julieta V; Giacomelli, Jorge I; Gómez, María C; Chan, Raquel L

    2016-11-22

    Homeodomain-leucine zipper (HD-Zip) transcription factors are unique to the plant kingdom; members of subfamily I are known to be involved in abiotic stress responses. HaHB11 belongs to this subfamily and it was previously shown that it is able to confer improved yield and tolerance to flooding via a quiescent strategy. Here we show that HaHB11 expression is induced by ABA, NaCl and water deficit in sunflower seedlings and leaves. Arabidopsis transgenic plants expressing HaHB11, controlled either by its own promoter or by the constitutive 35S CaMV, presented rolled leaves and longer roots than WT when grown under standard conditions. In addition, these plants showed wider stems and more vascular bundles. To deal with drought, HaHB11 transgenic plants closed their stomata faster and lost less water than controls, triggering an enhanced tolerance to such stress condition and also to salinity stress. Concomitantly, ABA-synthesis and sensing related genes were differentially regulated in HaHB11 transgenic plants. Either under long-term salinity stress or mild drought stress, HaHB11 transgenic plants did not exhibit yield penalties. Moreover, alfalfa transgenic plants were generated which also showed enhanced drought tolerance. Altogether, the results indicated that HaHB11 was able to confer drought and salinity tolerance via a complex mechanism which involves morphological, physiological and molecular changes.

  11. Visceral fat area is associated with HbA1c but not dialysate-related glucose load in nondiabetic PD patients

    NASA Astrophysics Data System (ADS)

    Ho, Li-Chun; Yen, Chung-Jen; Chao, Chia-Ter; Chiang, Chih-Kang; Huang, Jenq-Wen; Hung, Kuan-Yu

    2015-08-01

    Factors associated with increased visceral fat area (VFA) have been well documented in the general population but rarely explored in nondiabetic individuals on peritoneal dialysis (PD). As glycosylated hemoglobin (HbA1c) is positively correlated with VFA in diabetic patients, we hypothesized that the same correlation would exist in nondiabetic PD patients. We enrolled 105 nondiabetic patients who had undergone chronic PD for more than 3 months. Each subject underwent an abdominal computed tomography (CT) scan, and the umbilicus cut was analyzed for VFA. VFA values, corrected for body mass index and subjected to natural logarithm transformations, were examined to determine whether they were correlated with HbA1c and other parameters. PD dialysates prescribed at the time of enrollment were recorded to calculate glucose load. We found that when 105 nondiabetic PD patients were classified according to tertiles of HbA1c, higher HbA1c was associated with larger VFA. Multiple linear regression analysis revealed that HbA1c was an independent determinant of VFA, while glucose load and other PD-specific factors were not. In summary, HbA1c, but not PD-related glucose load, was positively correlated with VFA in nondiabetic PD patients, suggesting clinical utility of HbA1c in the PD population.

  12. Efficacy of metabolic surgery on HbA1c decrease in type 2 diabetes mellitus patients with BMI <35 kg/m2--a review.

    PubMed

    Ngiam, Kee Yuan; Lee, Wei-Jei; Lee, Yi-Chih; Cheng, Anton

    2014-01-01

    High glycated hemoglobin A1c (HbA1c) is strongly correlated with developing type 2 diabetes mellitus (T2DM) complications; this study reviews the efficacy of various types of metabolic surgeries in reducing HbA1c levels in type 2 diabetics with BMI <35 kg/m(2). An electronic search of MEDLINE databases using terms 'metabolic surgery', type 2 diabetes mellitus, BMI <35 kg/m(2), and related keywords for studies published between 1987 and 2013. Data from 53 articles with 2,258 patients were selected for this review. The weighted mean change in HbA1c was -2.8 % (95 % CI -2.8 to -2.7, p < 0.01) and weighted mean BMI change was -5.5 kg/m(2) (95 % CI -5.6 to -5.4, p < 0.01). There was a strong correlation between weighted percentage mean change in HbA1c and BMI. Adjustable gastric banding and duodenal jejunal bypass were inferior to other surgeries in reducing BMI and HbA1c in BMI <35 kg/m(2). Metabolic surgery significantly decreases HbA1c in T2DM patients with BMI <35 kg/m(2) and that the magnitude of HbA1c change may be a useful surrogate of DM control.

  13. Gq protein mediates UVB-induced cyclooxygenase-2 expression by stimulating HB-EGF secretion from HaCaT human keratinocytes

    SciTech Connect

    Seo, MiRan; Juhnn, Yong-Sung

    2010-03-05

    Ultraviolet (UV) radiation induces cyclooxygenase-2 expression to produce cellular responses including aging and carcinogenesis in skin. We hypothesised that heterotrimeric G proteins mediate UV-induced COX-2 expression by stimulating secretion of soluble HB-EGF (sHB-EGF). In this study, we aimed to elucidate the role and underlying mechanism of the {alpha} subunit of Gq protein (G{alpha}q) in UVB-induced HB-EGF secretion and COX-2 induction. We found that expression of constitutively active G{alpha}q (G{alpha}qQL) augmented UVB-induced HB-EGF secretion, which was abolished by knockdown of G{alpha}q with shRNA in HaCaT human keratinocytes. G{alpha}q was found to mediate the UVB-induced HB-EGF secretion by sequential activation of phospholipase C (PLC), protein kinase C{delta} (PKC{delta}), and matrix metaloprotease-2 (MMP-2). Moreover, G{alpha}qQL mediated UVB-induced COX-2 expression in an HB-EGF-, EGFR-, and p38-dependent manner. From these results, we concluded that G{alpha}q mediates UV-induced COX-2 expression through activation of EGFR by HB-EGF, of which ectodomain shedding was stimulated through sequential activation of PLC, PKC{delta} and MMP-2 in HaCaT cells.

  14. Value of the combined examination of Cys-C and HbA1c for diagnosis of early renal injury in pediatric diabetes

    PubMed Central

    Qian, Tong; Tian, Lijun; Li, Yanyan; Zhang, Zhenru; Tian, Xiuying; Sun, Dan

    2017-01-01

    The objective of the present study was to evaluate the combined application of measuring cystatin C (Cys-C) and hemoglobin A1c (HbA1c) levels for early renal injury in pediatric patients with type 2 diabetes. A total of 130 children with type 2 diabetes admitted to our hospital from May 2013 to July 2015 were selected. Patients were divided according to whether there was complication of renal injury. In group A (n=65), the patients had renal injury and in group B (n=65), the patients did not have renal injury. The levels of Cys-C and HbA1c in the two groups were examined. The results showed that the levels of Cys-C and HbA1c of patients in group A were significantly higher than those in group B (P<0.05), and the positive rate of the combined examination of Cys-C and HbA1c in group A was 92.3%, and was higher than that of the individual examinations of either Cys-C or HbA1c (P<0.05). The Spearman's correlation coefficient analysis was applied to group B and showed that Cys-C was positively correlated with HbA1c (r=0.842, P<0.05). From analysis of the receiver operating characteristic curves, the combined examination of Cys-C and HbA1c surpassed the individual examinations of Cys-C or HbA1c in sensitivity and specificity (P<0.05). In conclusion, the positive detection rate of early renal injury was significantly increased by the combined examination of Cys-C and HbA1c in pediatric patients with type 2 diabetes, which is beneficial for early identification and diagnosis of this diseases and is worthy of clinical application.

  15. Effects of canagliflozin on body weight and relationship to HbA1c and blood pressure changes in patients with type 2 diabetes

    PubMed Central

    Stenlöf, Kaj; Leiter, Lawrence A.; Wilding, John P. H.; Blonde, Lawrence; Polidori, David; Xie, John; Sullivan, Daniel; Usiskin, Keith; Canovatchel, William; Meininger, Gary

    2016-01-01

    Aims/hypothesis Canagliflozin, a sodium glucose co-transporter 2 inhibitor, reduces HbA1c, body weight and systolic BP (SBP) in patients with type 2 diabetes. As weight loss is known to reduce both HbA1c and SBP, these analyses were performed to evaluate the contribution of weight loss resulting from treatment with canagliflozin to HbA1c and SBP reductions in patients with type 2 diabetes. Methods Pooled data from four placebo-controlled Phase 3 studies (N=2,250) in patients with type 2 diabetes were used in the analyses. In each study, patients were treated with placebo, canagliflozin 100 mg or canagliflozin 300 mg, once daily for 26 weeks. Changes from baseline in body weight, HbA1c and SBP were measured at week 26, and the contribution of weight loss to the lowering of HbA1c and SBP was obtained using ANCOVA. Results Canagliflozin 100 and 300 mg reduced mean body weight, HbA1c and SBP compared with placebo (p<0.001 for each), and more patients had body-weight reductions >0%, ≥5% and ≥10% with canagliflozin treatment than with placebo. Weight-loss-independent and weight-loss-associated mechanisms contributed to HbA1c and SBP lowering with canagliflozin: ~85% of HbA1c lowering and ~60% of SBP lowering was independent of weight loss. Conclusions/interpretation In patients with type 2 diabetes, canagliflozin provided clinically meaningful body-weight reductions, and the weight loss contributed to reductions in HbA1c and SBP. Trial registration ClinicalTrials.gov NCT01081834; NCT01106625; NCT01106677; and NCT01106690 PMID:25813214

  16. The Natural History of Hb S/Hereditary Persistence of Fetal Hemoglobin in 13 Children from the State of Minas Gerais, Brazil.

    PubMed

    Belisário, André R; Sales, Rahyssa R; Silva, Célia M; Velloso-Rodrigues, Cibele; Viana, Marcos Borato

    2016-06-01

    Children with Hb S (HBB: c.20A > T)/hereditary persistence of fetal hemoglobin (Hb S/HPFH) have a mild clinical phenotype, but some complications have been reported. The natural history of Hb S/HPFH in children from the State of Minas Gerais, Brazil newborn cohort is described. Clinical and hematological data regarding participants' phenotypes were retrieved from medical records. The HPFH-1, HPFH-2, and HPFH-3 and α-thalassemia (α-thal) deletions were detected by gap-polymerase chain reaction (gap-PCR). Thirteen children were included, nine (69.2%) had the Hb S/HPFH-2 deletion, and four (30.8%) had Hb S/HPFH-1 deletion; 11 children (84.6%) had αα/αα, and two (15.4%) carried the αα/-α(3.7) (rightward) deletion. The mean concentration of total hemoglobin (Hb) and Hb F was 12.52 ± 0.56 g/dL and 42.31% ± 1.97%, respectively. Mild microcytosis and hypochromia were observed. We found acute clinical manifestations of sickle cell disease, such as acute chest syndrome (ACS) and acute pain crisis in four children; nine (69.2%) children were completely asymptomatic during the follow-up period. All children were classified as having low-risk transcranial Doppler (TDC). In conclusion, children with Hb S/HPFH have a mild clinical phenotype of sickle cell disease, although acute clinical manifestations may occur. High Hb F levels and absence of anemia are common hematological characteristics.

  17. Does Iron Deficiency Anaemia and its Severity Influence HbA1C Level in Non Diabetics? An Analysis of 150 Cases

    PubMed Central

    Ganapathy, Shivashekar; Arunachalam, Sundaram; Raja, Veena; Ramraj, Balaji

    2017-01-01

    Introduction Anaemia has a high prevalence having great impact worldwide and potentially contributing to the pathogenesis of various chronic diseases. Approximately 1/3rd of patients with anaemia have iron deficiency. American Diabetes Association (ADA) has affirmed Glycated Haemoglobin (HbA1C) ≥ 6.5% as a diagnostic criterion for Diabetes Mellitus (DM). Variation of HbA1C in Iron Deficiency Anaemia (IDA) has clashing results. Aim To decide the impact of IDA on HbA1C levels among non diabetics. To assess and analyse the variation of HbA1C according to the degree of anaemia (mild, moderate and severe). Materials and Methods This cross-sectional study was carried out in SRM Medical College Hospital and Research Centre, Chennai, Tamil Nadu from February 2016 to October 2016 and approved by our Institutional Ethical Committee. Totally 150 non diabetics (75 with IDA and 75 without IDA) were included in this study. Medical history was recorded and HbA1C, Haemoglobin (Hb), Haematocrit (Hct), red cell indices, serum iron, ferritin and Fasting Plasma Glucose (FPG) were tested. Results The IDA patients in this study had a mean HbA1C (6.84±0.07%) which was higher than the non anaemic group (5.12±0.04%) and this difference was statistically significant (p< 0.05). HbA1C level was increased when severity of anaemia worsened. Also, noteworthy statistical significance was observed between no anaemia, mild, moderate and severe anaemia (p< 0.05). Conclusion In this study, we observed a positive correlation between IDA and elevated HbA1C level in non-diabetic population.

  18. Boussinesq modeling of HB06 tracer releases Part 1: Wave and current model-data comparisons

    NASA Astrophysics Data System (ADS)

    Feddersen, F.; Clark, D. B.; Guza, R. T.

    2010-12-01

    During the HB06 experiment (Fall 2006 at Huntington Beach), a cross-shore array of current meters and pressure sensors were deployed from the shoreline to 4-m depth to make Eulerian wave and current measurements. Five dye tracer releases were performed. In each, the mean tracer plume was advected alongshore and dispersed in the cross-shore in a manner consistent with a wall bounded plume [Clark et al. JGR, in press 2010]. The mechanisms of horizontal tracer dispersion are complex and include mixing by breaking waves and stirring by the horizontal eddy field that is driven by both shear-waves and finite-crest-length breaking due to directionally-spread waves. Thus acurate simulation of surfzone tracer evolution requires a model that resolves that resolves individual waves such as the time-dependent Boussinesq model funwaveC. Such models have not been extensively validated with field observations. Prior to simulating the time- and spatial-dependent evolution of a surfzone tracer field (Part 2), the model is first used to simulate the wave and current conditions during the 5 dye releases (Part 1). The observed bathymetery is used with a shoreline sponge layer (at typically 0.25 m depth) to absorb excess wave anergy. The modeled random and directionally spread wave field is forced approximately 350 m offshore in 7 m depth with O(1000) discrete frequencies. Standard values of the model coefficients for wave breaking and bottom friction are chosen. For the 5 tracer releases, the model is run for roughly 3 hours. With the inputs of the observed bathymetry and the offshore wave spectra, the Boussinesq model funwaveC reproduces well the 1. cross-shore structure of signficant wave height, wave angle, and directional spread and 2. the cross-shore evolution of the wave spectra in the sea-swell band from outside the surfzone through the surfzone The good Eulerian model-data agreement demonstrates that the funwaveC model may be useful in understanding and characterizing surfzone

  19. A detailed study of the structure of the nested planetary nebula, Hb 12, the Matryoshka nebula

    SciTech Connect

    Clark, D. M.; López, J. A.; Edwards, M. L.; Winge, C. E-mail: jal@astrosen.unam.mx E-mail: cwinge@gemini.edu

    2014-11-01

    We present near-IR, integral field spectroscopic observations of the planetary nebula (PN) Hb 12 using Near-infrared Integral Field Spectrograph (NIFS) on Gemini-North. Combining NIFS with the adaptive optics system Altair, we provide a detailed study of the core and inner structure of this PN. We focus the analysis in the prominent emission lines [Fe II] (1.6436 μm), He I (2.0585 μm), H{sub 2} (2.1214 μm), and Br{sub γ} (2.16553 μm). We find that the [Fe II] emission traces a tilted system of bipolar lobes, with the northern lobe being redshifted and the southern lobe blueshifted. The [Fe II] emission is very faint at the core and only present close to the systemic velocity. There is no H{sub 2} emission in the core, whereas the core is prominent in the He I and Br{sub γ} recombination lines. The H{sub 2} emission is concentrated in equatorial arcs of emission surrounding the core and expanding at ∼30 km s{sup –1}. These arcs are compared with Hubble Space Telescope images and shown to represent nested loops belonging to the inner sections of a much larger bipolar structure that replicates the inner one. The He I and Br{sub γ} emission from the core clearly show a cylindrical central cavity that seems to represent the inner walls of an equatorial density enhancement or torus. The torus is 0.''2 wide (≡200 AU radius at a distance of 2000 pc) and expanding at ≤30 km s{sup –1}. The eastern wall of the inner torus is consistently more intense than the western wall, which could indicate the presence of an off-center star, such as is observed in the similar hourglass PN, MyCn 18. A bipolar outflow is also detected in Br{sub γ} emerging within 0.''1 from the core at ∼ ± 40 km s{sup –1}.

  20. Using Automated HbA1c Testing to Detect Diabetes Mellitus in Orthopedic Inpatients and Its Effect on Outcomes

    PubMed Central

    Ekinci, Elif I.; Kong, Alvin; Churilov, Leonid; Nanayakkara, Natalie; Chiu, Wei Ling; Sumithran, Priya; Djukiadmodjo, Frida; Premaratne, Erosha; Owen-Jones, Elizabeth; Hart, Graeme Kevin; Robbins, Raymond; Hardidge, Andrew; Johnson, Douglas; Baker, Scott T.; Zajac, Jeffrey D.

    2017-01-01

    Aims The prevalence of diabetes is rising, and people with diabetes have higher rates of musculoskeletal-related comorbidities. HbA1c testing is a superior option for diabetes diagnosis in the inpatient setting. This study aimed to (i) demonstrate the feasibility of routine HbA1c testing to detect the presence of diabetes mellitus, (ii) to determine the prevalence of diabetes in orthopedic inpatients and (iii) to assess the association between diabetes and hospital outcomes and post-operative complications in orthopedic inpatients. Methods All patients aged ≥54 years admitted to Austin Health between July 2013 and January 2014 had routine automated HbA1c measurements using automated clinical information systems (CERNER). Patients with HbA1c ≥6.5% were diagnosed with diabetes. Baseline demographic and clinical data were obtained from hospital records. Results Of the 416 orthopedic inpatients included in this study, 22% (n = 93) were known to have diabetes, 4% (n = 15) had previously unrecognized diabetes and 74% (n = 308) did not have diabetes. Patients with diabetes had significantly higher Charlson comorbidity scores compared to patients without diabetes (median, IQR; 1 [0,2] vs 0 [0,0], p<0.001). After adjusting for age, gender, comorbidity score and estimated glomerular filtration rate, no significant differences in the length of stay (IRR = 0.92; 95%CI: 0.79–1.07; p = 0.280), rates of intensive care unit admission (OR = 1.04; 95%CI: 0.42–2.60, p = 0.934), 6-month mortality (OR = 0.52; 95%CI: 0.17–1.60, p = 0.252), 6-month hospital readmission (OR = 0.93; 95%CI: 0.46–1.87; p = 0.828) or any post-operative complications (OR = 0.98; 95%CI: 0.53–1.80; p = 0.944) were observed between patients with and without diabetes. Conclusions Routine HbA1c measurement using CERNER allows for rapid identification of inpatients admitted with diabetes. More than one in four patients admitted to a tertiary hospital orthopedic ward have diabetes. No statistically

  1. Heterogeneous behavior of lipids according to HbA1c levels undermines the plausibility of metabolic syndrome in type 1 diabetes: data from a nationwide multicenter survey

    PubMed Central

    2012-01-01

    Background Cardiovascular risk factors (CVRF) may cluster in type 1 diabetes, analogously to the metabolic syndrome described in type 2 diabetes. The threshold of HbA1c above which lipid variables start changing behavior is unclear. This study aims to 1) assess the behavior of dyslipidemia according to HbA1c values; 2) detect a threshold of HbA1c beyond which lipids start to change and 3) compare the clustering of lipids and other non-lipid CVRF among strata of HbA1c individuals with type 1 diabetes. Methods Effects of HbA1c quintiles (1st: ≤7.4%; 2nd: 7.5-8.5%; 3rd: 8.6-9.6%; 4th: 9.7-11.3%; and 5th: >11.5%) and covariates (gender, BMI, blood pressure, insulin daily dose, lipids, statin use, diabetes duration) on dyslipidemia were studied in 1275 individuals from the Brazilian multi-centre type 1 diabetes study and 171 normal controls. Results Body size and blood pressure were not correlated to lipids and glycemic control. OR (99% CI) for high-LDL were 2.07 (1.21-3.54) and 2.51 (1.46-4.31), in the 4th and 5th HbA1c quintiles, respectively. Hypertriglyceridemia increased in the 5th quintile of HbA1c, OR 2.76 (1.20-6.37). OR of low-HDL-cholesterol were 0.48 (0.24-0.98) and 0.41 (0.19-0.85) in the 3rd and 4th HbA1c quintiles, respectively. HDL-cholesterol correlated positively (0.437) with HbA1c in the 3rd quintile. HDL-cholesterol and insulin dose correlated inversely in all levels of glycemic control. Conclusions Correlation of serum lipids with HbA1c is heterogeneous across the spectrum of glycemic control in type 1 diabetes individuals. LDL-cholesterol and triglycerides worsened alongside HbA1c with distinct thresholds. Association of lower HDL-cholesterol with higher daily insulin dose is consistent and it points out to a role of exogenous hyperinsulinemia in the pathophysiology of the CVRF clustering. These data suggest diverse pathophysiological processes depending on HbA1c, refuting a unified explanation for cardiovascular risk in type 1 diabetes. PMID

  2. Two new δ-globin gene variants: Hb A(2)-Saint-Etienne [δ14(A11)Leu→Pro (HBD: c.44T>C)] and Hb A(2)-Marseille [δ22(B4) Ala→Lys (HBD: c.67G>A;68C>A)].

    PubMed

    Joly, Philippe; Lacan, Philippe; Garcia, Caroline; Desbrée, Aurélie; Couprie, Nicole; Francina, Alain

    2013-01-01

    We report two new variants of the δ-globin gene: Hb A(2)-Saint-Etienne [δ14(A11)Leu→Pro] and Hb A(2)-Marseille [δ22(B4)Ala→Lys]. The first variant has a low rate of expression, the second results from a double nucleotide mutation on the same codon.

  3. The beta -globin recombinational hotspot reduces the effects of strong selection around HbC, a recently arisen mutation providing resistance to malaria.

    PubMed

    Wood, Elizabeth T; Stover, Daryn A; Slatkin, Montgomery; Nachman, Michael W; Hammer, Michael F

    2005-10-01

    Recombination is expected to reduce the effect of selection on the extent of linkage disequilibrium (LD), but the impact that recombinational hotspots have on sites linked to selected mutations has not been investigated. We empirically determine chromosomal linkage phase for 5.2 kb spanning the beta -globin gene and hotspot. We estimate that the HbC mutation, which is positively selected because of malaria, originated <5,000 years ago and that selection coefficients are 0.04-0.09. Despite strong selection and the recent origin of the HbC allele, recombination (crossing-over or gene conversion) is observed within 1 kb 5' of the selected site on more than one-third of the HbC chromosomes sampled. The rapid decay in LD upstream of the HbC allele demonstrates the large effect the ss-globin hotspot has in mitigating the effects of positive selection on linked variation.

  4. Effects of resuscitation with polymerized porcine hemoglobin (pPolyHb) on hemodynamic stability and oxygen delivery in a rat model of hemorrhagic shock.

    PubMed

    Wang, Li; Liu, Fang; Yan, Kunping; Pan, Wencan; Xu, Lijuan; Liu, Huifang; Yan, Chengbin; Chen, Chao; Zhu, Hongli

    2017-02-01

    The objective of this study was to evaluate the effects of polymerized porcine hemoglobin (pPolyHb) on hemodynamic stability and oxygen delivery in a rat model of hemorrhagic shock. Rats underwent controlled hemorrhage, resulting in the loss of 65% of their blood volume in 90 minutes. The results showed that pPolyHb was superior to hetastarch and saline, and similar to whole blood, in restoring hemodynamic stability and reversing anaerobic metabolism caused by hemorrhage. Furthermore, pPolyHb improved oxygen supply and increased blood oxygen content. These data suggest that pPolyHb can be effective in improving tissue perfusion under conditions of severe hemorrhagic shock.

  5. Diagnostic Dilemma of Hb Perth [β32(B14)Leu→Pro; HBB: c.98T > C] in Mainland China.

    PubMed

    Jiang, Hua; Yan, Jin-Mei; Li, Jian; Xie, Xing-Mei; Li, Dong-Zhi

    2016-06-01

    Unstable hemoglobin (Hb) variants represent a rare etiology of congenital hemolytic anemia. Correct diagnosis can be a challenge due to the relative rarity or lack of awareness of this disorder. We report an 18-month-old girl, who presented with a long-standing hemolytic anemia. Her diagnosis of unstable Hb Perth [β32(B14)Leu→Pro, HBB: c.98T > C] had not been made until gene sequencing of the β-globin gene was performed.

  6. Single-Use Disposable Electrochemical Label-Free Immunosensor for Detection of Glycated Hemoglobin (HbA1c) Using Differential Pulse Voltammetry (DPV).

    PubMed

    Molazemhosseini, Alireza; Magagnin, Luca; Vena, Pasquale; Liu, Chung-Chiun

    2016-07-01

    A single-use disposable in vitro electrochemical immunosensor for the detection of HbA1c in undiluted human serum using differential pulse voltammetry (DPV) was developed. A three-electrode configuration electrochemical biosensor consisted of 10-nm-thin gold film working and counter electrodes and a thick-film printed Ag/AgCl reference electrode was fabricated on a polyethylene terephthalate (PET) substrate. Micro-fabrication techniques including sputtering vapor deposition and thick-film printing were used to fabricate the biosensor. This was a roll-to-roll cost-effective manufacturing process making the single-use disposable in vitro HbA1c biosensor a reality. Self-assembled monolayers of 3-Mercaptopropionic acid (MPA) were employed to covalently immobilize anti-HbA1c on the surface of gold electrodes. Electrochemical impedance spectroscopy (EIS) and X-ray photoelectron spectroscopy (XPS) confirmed the excellent coverage of MPA-SAM and the upward orientation of carboxylic groups. The hindering effect of HbA1c on the ferricyanide/ferrocyanide electron transfer reaction was exploited as the HbA1c detection mechanism. The biosensor showed a linear range of 7.5-20 µg/mL of HbA1c in 0.1 M PBS. Using undiluted human serum as the test medium, the biosensor presented an excellent linear behavior (R² = 0.999) in the range of 0.1-0.25 mg/mL of HbA1c. The potential application of this biosensor for in vitro measurement of HbA1c for diabetic management was demonstrated.

  7. Influence of semisynthetic modification of the scaffold of a contact domain of HbS on polymerization: role of flexible surface topology in polymerization inhibition.

    PubMed

    Sonati, Srinivasulu; Bhutoria, Savita; Prabhakaran, Muthuchidambaran; Acharya, Seetharama A

    2017-03-01

    A new variant of HbS, HbS-Einstein with a deletion of segment α23-26 in the B-helix, has been assembled by semisynthetic approach. B-helix of the α chain of cis αβ-dimer of HbS plays dominant role in the quinary interactions of deoxy HbS dimer. This B-helix is the primary scaffold that provides the orientation for the side chains of contact residues of this intermolecular contact domain. The design of HbS-Einstein has been undertaken to map the influence of perturbation of molecular surface topology and the flexibility of surface residues in the polymerization. The internal deletion exerts a strong inhibitory influence on Val-6 (β)-dependent polymerization, comparable to single contact site mutations and not for complete neutralization of Val-6(β)-dependent polymerization. The scaffold modification in cis-dimer is inhibitory, and is without any effect when present on the trans dimer. The flexibility changes in the surface topology in the region of scaffold modification apparently counteracts the intrinsic polymerization potential of the molecule. The inhibition is close to that of Le Lamentin mutation [His-20 (α) → Gln] wherein a mutation engineered without much change in flexibility of the contact domain. Interestingly, the chimeric HbS with swine-human chimeric α chain with multiple non-conservative mutations completely inhibits the Val-6(β)-dependent polymerization. The deformabilities of surface topology of chimeric HbS are comparable to HbS in spite of the multiple contact site mutations in the α-chain. We conclude that the design of antisickling Hbs for gene therapy of sickle cell disease should involve multiple mutations of intermolecular contact sites.

  8. The metalloendopeptidase nardilysin (NRDc) is potently inhibited by heparin-binding epidermal growth factor-like growth factor (HB-EGF).

    PubMed Central

    Hospital, Véronique; Nishi, Eiichiro; Klagsbrun, Michael; Cohen, Paul; Seidah, Nabil G; Prat, Annik

    2002-01-01

    Nardilysin (N-arginine dibasic convertase, or NRDc) is a cytosolic and cell-surface metalloendopeptidase that, in vitro, cleaves substrates upstream of Arg or Lys in basic pairs. NRDc differs from most of the other members of the M16 family of metalloendopeptidases by a 90 amino acid acidic domain (DAC) inserted close to its active site. At the cell surface, NRDc binds heparin-binding epidermal growth factor-like growth factor (HB-EGF) and enhances HB-EGF-induced cell migration. An active-site mutant of NRDc fulfills this function as well as wild-type NRDc, indicating that the enzyme activity is not required for this process. We now demonstrate that NRDc starts at Met(49). Furthermore, we show that HB-EGF not only binds to NRDc but also potently inhibits its enzymic activity. NRDc-HB-EGF interaction involves the 21 amino acid heparin-binding domain (P21) of the growth factor, the DAC of NRDc and most probably its active site. Only disulphide-bonded P21 dimers are inhibitory. We also show that Ca(2+), via the DAC, regulates both NRDc activity and HB-EGF binding. We conclude that the DAC is thus a key regulatory element for the two distinct functions that NRDc fulfills, i.e. as an HB-EGF modulator and a peptidase. PMID:12095415

  9. HbNIN2, a cytosolic alkaline/neutral-invertase, is responsible for sucrose catabolism in rubber-producing laticifers of Hevea brasiliensis (para rubber tree).

    PubMed

    Liu, Shujin; Lan, Jixian; Zhou, Binhui; Qin, Yunxia; Zhou, Yihua; Xiao, Xiaohu; Yang, Jianghua; Gou, Jiqing; Qi, Jiyan; Huang, Yacheng; Tang, Chaorong

    2015-04-01

    In Hevea brasiliensis, an alkaline/neutral invertase (A/N-Inv) is responsible for sucrose catabolism in latex (essentially the cytoplasm of rubber-producing laticifers, the source of natural rubber) and implicated in rubber yield. However, neither the gene encoding this enzyme nor its molecular and biochemical properties have been well documented. Three Hevea A/N-Inv genes, namely HbNIN1, 2 and 3, were first cloned and characterized in planta and in Escherichia coli. Cellular localizations of HbNIN2 mRNA and protein were probed. From latex, active A/N-Inv proteins were purified, identified, and explored for enzymatic properties. HbNIN2 was identified as the major A/N-Inv gene functioning in latex based on its functionality in E. coli, its latex-predominant expression, the conspicuous localization of its mRNA and protein in the laticifers, and its expressional correlation with rubber yield. An active A/N-Inv protein was partially purified from latex, and determined as HbNIN2. The enhancement of HbNIN2 enzymatic activity by pyridoxal is peculiar to A/N-Invs in other plants. We conclude that HbNIN2, a cytosolic A/N-Inv, is responsible for sucrose catabolism in rubber laticifers. The results contribute to the studies of sucrose catabolism in plants as a whole and natural rubber synthesis in particular.

  10. The hematologic characteristics of sickle cell anemia bearing the Bantu haplotype: the relationship between G gamma and HbF level.

    PubMed

    Nagel, R L; Rao, S K; Dunda-Belkhodja, O; Connolly, M M; Fabry, M E; Georges, A; Krishnamoorthy, R; Labie, D

    1987-04-01

    Previous work has demonstrated that the HbS gene has appeared and expanded three times in Africa in three separate geographic locations and that these three distinct mutational events can be identified by linked DNA polymorphic sites (haplotypes) surrounding the abnormal gene. We have reported that the Senegalese and Beninian haplotypes differ in G gamma expression, mean percentage of HbF, and percentage of dense cells. We now report on the third haplotype, the Bantu, and find that it has intermediate features, namely, the high mean percentage of HbF and low percentage of dense cells associated with the Senegalese haplotype, but with a low percentage of G gamma expression similar to the Beninian haplotype. The distribution of percent HbF is quite different from Senegal haplotype-bearing sickle cell anemia patients since it covers a much wider range. The low G gamma expression is also different from the Beninians since it contains a significant and unique cluster of individuals with lower than 38% G gamma. Interestingly, among the Bantu there is a strong correlation between HbF levels and G gamma expression, which is not seen with the other haplotypes. These findings open the possibility that among the Bantu haplotype-bearing individuals two chromosomal types exist that define different levels of G gamma and HbF expression. Further structural exploration of these two potential subhaplotypes is needed.

  11. Association of high normal HbA1c and TSH levels with the risk of CHD: a 10-year cohort study and SVM analysis

    PubMed Central

    Li, Hui; Cui, Ying; Zhu, Yanan; Yan, Haiying; Xu, Wenge

    2017-01-01

    This study aimed to determine the association between the clinical reference range of serum glycated hemoglobin A1c (HbA1c) and thyrotropin (TSH) and the risk of coronary heart disease (CHD) in non-diabetic and euthyroid patients. We examined baseline HbA1c and TSH in 538 healthy participants, and then analyzed the associations and potential value of these indicators for predicting CHD using Cox proportional hazard and support vector machine analyses. During the median follow-up of 120 months, 39 participants later developed CHD. The baseline HbA1c and TSH within the reference range were positively associated with CHD risk. No correlation and interaction were found between the baseline HbA1c and TSH for the development of CHD. Disease event-free survival varied among participants with different baseline HbA1c quintiles, whereas disease event-free survival was similar for different TSH tertiles. The combination of these baselines showed sensitivity of 87.2%, specificity of 92.7%, and accuracy of 92.3% for identifying the participants who will later develop CHD. Relatively high but clinically normal HbA1c and TSH levels may increase the risk of CHD. Therefore, the combination of these indicators can serve as a biomarker for identifying healthy individuals from those who would later develop CHD. PMID:28345646

  12. Hb San Cataldo [β144(HC1)Lys→Thr; HBB: C.434A > C]: A New Hemoglobin Variant with Increased Affinity for Oxygen.

    PubMed

    Vinciguerra, Margherita; Passarello, Cristina; Cassarà, Filippo; Leto, Filippo; Cannata, Monica; Crivello, Anna; Di Salvo, Veronica; Maggio, Aurelio; Giambona, Antonino

    2016-08-01

    A 59-year-old Italian woman came to our center for revaluation of a previous diagnosis of polycythemia vera. The patient presented with a lifelong history of polycythemia, no increase in white blood cells (WBCs) and platelets, and a negative bone marrow biopsy. Analysis of hemoglobin (Hb) fractions showed an abnormal fast moving Hb component. We aimed to determine if this variant was the cause of polycythemia in this patient. A complete blood count (CBC) was performed by an automated cell counter and Hb fractions were determined by high performance liquid chromatography (HPLC). Standard stability tests and oxygen affinity evaluation were also performed. Genomic DNA was extracted from peripheral blood leukocytes using the phenol chloroform method and the entire β-globin gene was analyzed by direct sequencing. At the hematological level, no anemia or hemolysis was observed but an abnormal Hb fraction was detected using cation exchange HPLC. Molecular analysis of the β-globin gene showed heterozygosity for an AAG > ACG substitution at codon 144, resulting in a Lys→Thr amino acid replacement. We demonstrated that this is a new Hb variant with increased oxygen affinity. Its altered physiology is caused by the reduction of 2,3-diphosphoglycerate (2,3-DPG) effects, due to an amino acid substitution in the central pocket near the C-terminal of the β chain. We called this new variant Hb San Cataldo for the native city of proband.

  13. New analytical tools and epidemiological data for the identification of HbA2 borderline subjects in the screening for beta-thalassemia.

    PubMed

    Mosca, Andrea; Paleari, Renata; Galanello, Renzo; Sollaino, Carla; Perseu, Lucia; Demartis, Franca Rosa; Passarello, Cristina; Giambona, Antonino; Maggio, Aurelio

    2008-08-01

    The increase of HbA(2) is the most important feature in the identification of beta-thalassemia carriers. However, some carriers are difficult to identify, because the level of HbA(2) is not in the typical range. Few data are available concerning the prevalence of such unusual phenotypes, and knowing their expected prevalence could be helpful in detecting systematic drifts in the analytical systems for HbA(2) quantification. In this study we report a retrospective investigation in two centres with high prevalence of beta-thalassemia. The prevalence of borderline subjects was found to be 2.2 and 3.0%, respectively. The genotypes of a subgroup of these subjects were then analyzed and in about 25% of cases a mutation in the globin genes was identified. We conclude that the occurrence of HbA(2) borderline phenotypes is not a rare event. In order to obtain more accurate HbA(2) measurements the development of an international reference measurement system for HbA(2), based on quantitative peptide mapping, has been recently started. We believe that the innovative approach of our method could also be used as a model to develop accurate quantitative methods for other red cell proteins relevant to the biodynamic properties and the surface electrochemistry of erythrocytes.

  14. Association of high normal HbA1c and TSH levels with the risk of CHD: a 10-year cohort study and SVM analysis.

    PubMed

    Li, Hui; Cui, Ying; Zhu, Yanan; Yan, Haiying; Xu, Wenge

    2017-03-27

    This study aimed to determine the association between the clinical reference range of serum glycated hemoglobin A1c (HbA1c) and thyrotropin (TSH) and the risk of coronary heart disease (CHD) in non-diabetic and euthyroid patients. We examined baseline HbA1c and TSH in 538 healthy participants, and then analyzed the associations and potential value of these indicators for predicting CHD using Cox proportional hazard and support vector machine analyses. During the median follow-up of 120 months, 39 participants later developed CHD. The baseline HbA1c and TSH within the reference range were positively associated with CHD risk. No correlation and interaction were found between the baseline HbA1c and TSH for the development of CHD. Disease event-free survival varied among participants with different baseline HbA1c quintiles, whereas disease event-free survival was similar for different TSH tertiles. The combination of these baselines showed sensitivity of 87.2%, specificity of 92.7%, and accuracy of 92.3% for identifying the participants who will later develop CHD. Relatively high but clinically normal HbA1c and TSH levels may increase the risk of CHD. Therefore, the combination of these indicators can serve as a biomarker for identifying healthy individuals from those who would later develop CHD.

  15. The metalloendopeptidase nardilysin (NRDc) is potently inhibited by heparin-binding epidermal growth factor-like growth factor (HB-EGF).

    PubMed

    Hospital, Véronique; Nishi, Eiichiro; Klagsbrun, Michael; Cohen, Paul; Seidah, Nabil G; Prat, Annik

    2002-10-01

    Nardilysin (N-arginine dibasic convertase, or NRDc) is a cytosolic and cell-surface metalloendopeptidase that, in vitro, cleaves substrates upstream of Arg or Lys in basic pairs. NRDc differs from most of the other members of the M16 family of metalloendopeptidases by a 90 amino acid acidic domain (DAC) inserted close to its active site. At the cell surface, NRDc binds heparin-binding epidermal growth factor-like growth factor (HB-EGF) and enhances HB-EGF-induced cell migration. An active-site mutant of NRDc fulfills this function as well as wild-type NRDc, indicating that the enzyme activity is not required for this process. We now demonstrate that NRDc starts at Met(49). Furthermore, we show that HB-EGF not only binds to NRDc but also potently inhibits its enzymic activity. NRDc-HB-EGF interaction involves the 21 amino acid heparin-binding domain (P21) of the growth factor, the DAC of NRDc and most probably its active site. Only disulphide-bonded P21 dimers are inhibitory. We also show that Ca(2+), via the DAC, regulates both NRDc activity and HB-EGF binding. We conclude that the DAC is thus a key regulatory element for the two distinct functions that NRDc fulfills, i.e. as an HB-EGF modulator and a peptidase.

  16. Markers of glycemic control in the mouse: comparisons of 6-h- and overnight-fasted blood glucoses to Hb A1c.

    PubMed

    Han, Byoung Geun; Hao, Chuan-Ming; Tchekneva, Elena E; Wang, Ying-Ying; Lee, Chieh Allen; Ebrahim, Benyamin; Harris, Raymond C; Kern, Timothy S; Wasserman, David H; Breyer, Matthew D; Qi, Zhonghua

    2008-10-01

    The present studies examined the relationship between fasting blood glucose and Hb A(1c) in C57BL/6J, DBA/2J, and KK/HlJ mice with and without diabetes mellitus. Daily averaged blood glucose levels based on continuous glucose monitoring and effects of 6-h vs. overnight fasting on blood glucose were determined. Daily averaged blood glucose levels were highly correlated with Hb A(1c), as determined with a hand-held automated device using an immunodetection method. R(2) values were 0.90, 0.95, and 0.99 in KK/HIJ, C57BL/6J, and DBA/2J, respectively. Six-hour fasting blood glucose correlated more closely with the level of daily averaged blood glucose and with Hb A(1c) than did blood glucose following an overnight fast. To validate the immunoassay-determined Hb A(1c), we also measured total glycosylated hemoglobin using boronate HPLC. Hb A(1c) values correlated well with total glycosylated hemoglobin in all three strains but were relatively lower than total glycosylated hemoglobin in diabetic DBA/2J mice. These results show that 6-h fasting glucose provides a superior index of glycemic control and correlates more closely with Hb A(1c) than overnight-fasted blood glucose in these strains of mice.

  17. Constitutive expression of Campylobacter jejuni truncated hemoglobin CtrHb improves the growth of Escherichia coli cell under aerobic and anaerobic conditions.

    PubMed

    Yang, Jiang-Ke; Xiong, Wei; Xu, Li; Li, Jia; Zhao, Xiu-Ju

    2015-01-01

    Bacteria hemoglobin could bind to the oxygen, transfer it from the intracellular microenvironment to the respiration process and sustain the energy for the metabolism and reproduction of cells. Heterologous expression of bacteria hemoglobin gene could improve the capacity of the host on oxygen-capturing and allow it to grow even under microaerophilic condition. To develop a system based on hemoglobin to help bacteria cells overcome the oxygen shortage in fermentation, in this study, Campylobacter jejuni truncated hemoglobin (CtrHb) gene was synthesized and expressed under the control of constitutive expression promoters P2 and P(SPO1-II) in Escherichia coli. As showed by the growth curves of the two recombinants P2-CtrHb and P(SPO1-II)-CtrHb, constitutive expression of CtrHb improved cell growth under aerobic shaking-flasks, anaerobic capped-bottles and bioreactor conditions. According to the NMR analysis, this improvement might come from the expression of hemoglobin which could boost the metabolism of cells by supplying more oxygen to the respiratory chain processes. Through semi-quantitative RT-PCR and CO differential spectrum assays, we further discussed the connection between the growth patterns of the recombinants, the expression level of CtrHb and oxygen binding capacity of CtrHb in cells. Based on the growth patterns of these recombinants in bioreactor, a possible choice on different type of recombinants under specific fermentation conditions was also suggested in this study.

  18. Salinomycin efficiency assessment in non-tumor (HB4a) and tumor (MCF-7) human breast cells.

    PubMed

    Niwa, Andressa Megumi; D Epiro, Gláucia Fernanda Rocha; Marques, Lilian Areal; Semprebon, Simone Cristine; Sartori, Daniele; Ribeiro, Lúcia Regina; Mantovani, Mário Sérgio

    2016-06-01

    The search for anticancer drugs has led researchers to study salinomycin, an ionophore antibiotic that selectively destroys cancer stem cells. In this study, salinomycin was assessed in two human cell lines, a breast adenocarcinoma (MCF-7) and a non-tumor breast cell line (HB4a), to verify its selective action against tumor cells. Real-time assessment of cell proliferation showed that HB4a cells are more resistant to salinomycin than MCF-7 tumor cell line, and these data were confirmed in a cytotoxicity assay. The half maximal inhibitory concentration (IC50) values show the increased sensitivity of MCF-7 cells to salinomycin. In the comet assay, only MCF-7 cells showed the induction of DNA damage. Flow cytometric analysis showed that cell death by apoptosis/necrosis was only induced in the MCF-7 cells. The increased expression of GADD45A and CDKN1A genes was observed in all cell lines. Decreased expression of CCNA2 and CCNB1 genes occurred only in tumor cells, suggesting G2/M cell cycle arrest. Consequently, cell death was activated in tumor cells through strong inhibition of the antiapoptotic genes BCL-2, BCL-XL, and BIRC5 genes in MCF-7 cells. These data demonstrate the selectivity of salinomycin in killing human mammary tumor cells. The cell death observed only in MCF-7 tumor cells was confirmed by gene expression analysis, where there was downregulation of antiapoptotic genes. These data contribute to clarifying the mechanism of action of salinomycin as a promising antitumor drug and, for the first time, we observed the higher resistance of HB4a non-tumor breast cells to salinomycin.

  19. Associations between serum hepcidin, ferritin and Hb concentrations and type 2 diabetes risks in a Han Chinese population.

    PubMed

    Guo, Xin; Zhou, Daizhan; An, Peng; Wu, Qian; Wang, Hao; Wu, Aimin; Mu, Mingdao; Zhang, Di; Zhang, Zhou; Wang, Hui; He, Lin; Liu, Yun; Wang, Fudi

    2013-12-01

    Systemic Fe overload can contribute to abnormal glucose metabolism and the onset of type 2 diabetes (T2D). Although hepcidin is the master regulator of systemic Fe homeostasis, few studies have systematically evaluated the associations of serum hepcidin concentrations with Fe metabolism parameters and risks for the development of T2D. In this regard, whether hepcidin concentrations are associated with T2D remains controversial. We measured serum hepcidin and ferritin concentrations in a case-control study of 1259 Han Chinese participants to evaluate the possible associations of serum hepcidin concentrations with Fe metabolism parameters and risks of T2D. Individuals with diabetes (n 555) and control participants (n 704) were recruited and serum hepcidin and ferritin concentrations were quantified. Additionally, selected biochemical and anthropometric variables were determined. A logistic regression analysis was performed to evaluate the association of serum hepcidin and ferritin concentrations with T2D. A linear regression analysis was used to test for associations between serum hepcidin and ferritin concentrations and a number of clinical, demographic and diabetes-associated variables. We found that serum hepcidin concentrations correlated with Hb and serum ferritin concentrations. No differences in hepcidin concentrations were found between the group with diabetes and the control group. Hepcidin concentrations were not significantly correlated with T2D risk factors. We also found that serum ferritin concentrations were elevated in individuals with diabetes and were positively correlated with both Hb concentrations and T2D risk factors. The present findings suggest that serum ferritin concentrations correlate with T2D risk factors, while serum hepcidin concentrations are positively associated with Hb and serum ferritin concentrations, but do not correlate with T2D.

  20. Identification of β-globin haplotypes linked to sickle hemoglobin (Hb S) alleles in Mazandaran province, Iran.

    PubMed

    Aghajani, Faeghe; Mahdavi, Mohammad Reza; Kosaryan, Mehrnoush; Mahdavi, Mehrad; Hamidi, Mohaddese; Jalali, Hossein

    2016-12-21

    Carrier frequency of the β(S) allele has been reported to be 0.19% in Mazandaran province, northern Iran. Haplotype analysis of the β(S) allele helps trace the origin of its encoded hemoglobin (Hb) variant, Hb S, in a region. The aim of this study was to investigate the haplotypes associated with β(S) alleles in Mazandaran province. Capillary electrophoresis was carried out to detect individuals suspected to have a βS allele(s). DNA analysis (PCR-RFLP) was used for final confirmation. To identify 5\\' to 3\\' β-globin gene cluster haplotypes associated with β(S) alleles, family linkage analysis was applied. Six polymorphic sites (HincII 5' to ε, XmnI 5' to (G)γ, HindIII in (G)γ, HindIII in (A)γ, HincII 3' to ψβ and AvaII in β) were investigated using the PCR-RFLP method. Five different haplotypes were linked to β(S) alleles, while β(A) alleles were associated with nine haplotypes. Among the β(S) alleles, 53.9% were associated with the Benin (----++) haplotype, and the Arab-Indian (+++-++) haplotype had the second-highest frequency (23%). Unlike southern provinces, where the Arab-Indian haplotype is prominent, the Benin haplotype is the most frequent haplotype in northern Iran, and this may represent a founder effect. Since the Benin haplotype does not carry the XmnI polymorphism 5' to the (G)γ gene, which is responsible for high expression of Hb F, a severe form of sickle cell disease can be anticipated in patients that are homozygous for the β(S) allele in the northern region.

  1. Sequence of the S-layer gene of Thermus thermophilus HB8 and functionality of its promoter in Escherichia coli.

    PubMed Central

    Faraldo, M M; de Pedro, M A; Berenguer, J

    1992-01-01

    The nucleotide sequence of the slpA gene, which is responsible for the synthesis of the S-layer protein of Thermus thermophilus HB8, is described. This gene is transcribed as a unit in which the coding region is preceded by a 127-base-long leader mRNA sequence. The promoter region is also recognized by the RNA polymerase of Escherichia coli because of the presence of homologous -35 and -10 boxes. Homologies with other promoters from Thermus spp. are also presented. Images PMID:1429468

  2. [Epidemiological studies of viral hepatitis with and without HB antigen by means of complex studies in families].

    PubMed

    Ionescu, T r; Telniceanu, A; Dreptate, N; Bărbulescu, V; Lăzărescu, V; Zamfirescu-Gheorghiu, M; Roşu, S; Miron, C

    1977-01-01

    The results of an epidemiological and laboratory investigation on 242 adults and children, who had come in contact with patients suffering from viral hepatitis (in the family or outside it), showed the importance of family contact and the role of routes of transmission other than the parenteral and transfusional ones in viral hepatitis with positive HB antigen. Attention is likewise drawn to the importance of the laboratory tests (classical enzymatic tests and immunoelectrodiffusion) in the detection of epidemogenic sources, represented by the subclinical forms of infection.

  3. Denaturation studies by fluorescence and quenching of thermophilic protein NAD+-glutamate dehydrogenase from Thermus thermophilus HB8.

    PubMed

    Ruiz, Jose L; Ferrer, Juan; Pire, Carmen; Llorca, Francisco I; Bonete, Maria José

    2003-04-01

    Fluorescence techniques have been used to study the structural characteristics of many proteins. The thermophilic enzyme NAD-glutamate dehydrogenase from Thermus thermophilus HB8 is found to be a hexameric enzyme. Fluorescence spectra of native and denatured protein and effect of denaturants as urea and guanidine hydrochloride on enzyme activity of thermophilic glutamate dehydrogenase (t-GDH) have been analyzed. Native t-GDH presents the maximum emission at 338 nm. The denaturation process is accompanied by an exposure to the solvent of the tryptophan residues, as manifested by the red shift of the emission maximum. Fluorescence quenching by external quenchers, KI and acrylamide, has also been carried out.

  4. Hb Lake Tapawingo [α46(CE4)Phe→Ser; HBA2:c.140T>C]: a new unstable α chain hemoglobin variant associated with low systemic arterial saturation.

    PubMed

    Guest, Erin M; Neville, Kathleen A; Hoyer, James D; Safo, Martin K; Garg, Uttam; Saunders, Carol J; Abdulmalik, Osheiza; Zwick, David L

    2011-01-01

    A new unstable α-globin variant was detected in a child with hypoxemia and anemia. The child's mother was found to carry the same mutation. The hemoglobin (Hb) variant co-eluted with Hb A(2) by cation exchange high performance liquid chromatography (HPLC) and appeared cathodal to Hb A and anodal to Hb F by isoelectric focusing. It represented less than 20% of the total Hb and was unstable by isopropanol testing. Gene sequencing identified a missense mutation on the α2 gene [HBA2:c.140T>C]. Oxygen dissociation and P(50) test results were normal.

  5. Paenibacillus larvae-Directed Bacteriophage HB10c2 and Its Application in American Foulbrood-Affected Honey Bee Larvae.

    PubMed

    Beims, Hannes; Wittmann, Johannes; Bunk, Boyke; Spröer, Cathrin; Rohde, Christine; Günther, Gabi; Rohde, Manfred; von der Ohe, Werner; Steinert, Michael

    2015-08-15

    Paenibacillus larvae is the causative agent of American foulbrood (AFB), the most serious honey bee brood bacterial disease. We isolated and characterized P. larvae-directed bacteriophages and developed criteria for safe phage therapy. Whole-genome analysis of a highly lytic virus of the family Siphoviridae (HB10c2) provided a detailed safety profile and uncovered its lysogenic nature and a putative beta-lactamase-like protein. To rate its antagonistic activity against the pathogens targeted and to specify potentially harmful effects on the bee population and the environment, P. larvae genotypes ERIC I to IV, representatives of the bee gut microbiota, and a broad panel of members of the order Bacillales were analyzed for phage HB10c2-induced lysis. Breeding assays with infected bee larvae revealed that the in vitro phage activity observed was not predictive of the real-life scenario and therapeutic efficacy. On the basis of the disclosed P. larvae-bacteriophage coevolution, we discuss the future prospects of AFB phage therapy.

  6. Crystallization and preliminary X-ray diffraction analysis of recombinant phosphoribosylpyrophosphate synthetase from the Thermophilic thermus thermophilus strain HB27

    NASA Astrophysics Data System (ADS)

    Abramchik, Yu. A.; Timofeev, V. I.; Muravieva, T. I.; Sinitsyna, E. V.; Esipov, R. S.; Kuranova, I. P.

    2017-01-01

    Phosphoribosylpyrophosphate synthetases (PRPP synthetases) are among the key enzymes essential for vital functions of organisms and are involved in the biosynthesis of purine and pyrimidine nucleotides, coenzymes, and the amino acids histidine and tryptophan. These enzymes are used in biotechnology for the combined chemoenzymatic synthesis of natural nucleotide analogs. Recombinant phosphoribosylpyrophosphate synthetase I from the thermophilic strain HB27 of the bacterium Thermus thermophilus ( T. th HB27) has high thermal stability and shows maximum activity at 75°C, due to which this enzyme holds promise for biotechnological applications. In order to grow crystals and study them by X-ray crystallography, an enzyme sample, which was produced using a highly efficient producer strain, was purified by affinity and gel-filtration chromatography. The screening of crystallization conditions was performed by the vapor-diffusion technique. The crystals of the enzyme suitable for X-ray diffraction were grown by the counter-diffusion method through a gel layer. These crystals were used to collect the X-ray diffraction data set at the SPring-8 synchrotron radiation facility (Japan) to 3-Å resolution. The crystals belong to sp. gr. P21 and have the following unitcell parameters: a = 107.7 Å, b = 112.6 Å, c = 110.2 Å, α = γ = 90°, β = 116.6°. The X-ray diffraction data set is suitable for determining the three-dimensional structure of the enzyme at 3.0-Å resolution.

  7. Secondary Sea-Blue Histiocytosis in a Patient with Transfusion Dependent HbE-Beta Thalassaemia and Osteosarcoma.

    PubMed

    Saad Eldeen Bakheet, Omayma; Yusof, Nurasyikin; Raja Zahratul, Azma; Ithnin, Azlin; Abdul Aziz, Suria; Alias, Hamidah

    2016-06-01

    Secondary sea-blue histiocytosis occurs more frequently than the primary form and occurs consequent to a wide range of metabolic and haematologic disorders including thalassaemia. We report an 18-year-old Chinese boy with transfusion-dependent HbE-beta thalassaemia who complained of pain and swelling at the left iliac crest region for 2 months duration. Physical examination revealed pallor with hepatosplenomegaly. Local examination revealed a huge swelling 12 cm × 12 cm in diameter, firm in consistency and tender. Histopathological examination of the mass revealed an osteosarcoma. His bone marrow aspirate showed numerous sea-blue histiocytes, the cytoplasm of which was closely packed with fine granules that stained blue with May-Grunwald-Giemsa. The nuclei were centrally located in some cells and displaced towards the periphery in other cells. There was no malignant cell infiltration in the marrow. The case is reported due to the co-incidental dual pathology in our patient (HbE-beta thalassaemia and osteosarcoma) and the unusual bone marrow finding of numerous sea-blue histiocytes.

  8. Treatment of E. coli HB101 and the tetM gene by Fenton's reagent and ozone in cow manure.

    PubMed

    Cengiz, Murat; Uslu, Merih Otker; Balcioglu, Isil

    2010-12-01

    The destruction of antibiotic-resistant microorganisms at the source of contamination is necessary due to their adverse effects and to their increasingly widespread occurrence in the environment. To address this problem, Fenton and ozone oxidation processes were applied to synthetically contaminated cow manure to remove the tetM gene and its host, Escherichia coli HB101. The efficiency of the processes was evaluated by enumeration of E. coli HB101 and by PCR amplification of the tetM gene. The results of this study show that 56.60% bacterial inactivation (corresponding to a 0.36 log reduction) was achieved by a Fenton reagent dose of 50 mM H(2)O(2) and 5 mM Fe(2+) without acidifying the manure. Despite the high organic content of cow manure, 98.50% bacterial inactivation (corresponding to a 1.83 log reduction) was obtained by the ozonation process with an applied dose of 3.125 mg ozone/g manure slurry. The PCR study revealed that the band intensity of the tetM gene gradually decreased by increasing the Fenton reagent and the applied ozone dose. However, significantly high doses of oxidants would be required to completely eliminate bacterial pollution in manure.

  9. Evaluation of the Clinton Electronics DS2100HB-ST 4 X 3 Aspect Ratio, 21-Inch Diagonal Monochrome Monitor

    NASA Astrophysics Data System (ADS)

    2000-04-01

    The Clinton Electronics DS2100HB-ST Monochrome CRT Monitor (2 1-inch CRT size, 19.0" viewable area; the selling price is 1995) is a relatively low cost, 1600 x 1280 pixel, monochrome gray scale monitor. It has good image quality and features that make it an attractive candidate display device for NIMA Imagery Exploitation Capability workstations. Based on results of our evaluation, NIDL certifies the Clinton Electronics DS2100HB-ST monochrome monitor as being suitable only for monoscopic, and not for stereo, operation in IEC workstations. NIDL rates this monochrome monitor as a 'B' for monoscopic mode and 'F' for stereo mode for the Image Analyst and Cartographer applications. In stereo, this monitor can produce a 1024 x 1024 stereo image at 59 Hz per eye, but it has only 47% of the maximum luminance and only 44% of the stereo extinction ratio required by the IEC Specifications. Clinton states that the primary market for this lower cost monitor is for clinical tasks and for training purposes. It is not intended for primary diagnoses of x-ray images.

  10. Omp85Tt from Thermus thermophilus HB27: an Ancestral Type of the Omp85 Protein Family▿

    PubMed Central

    Nesper, Jutta; Brosig, Alexander; Ringler, Philippe; Patel, Geetika J.; Müller, Shirley A.; Kleinschmidt, Jörg H.; Boos, Winfried; Diederichs, Kay; Welte, Wolfram

    2008-01-01

    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 protein, Omp85Tt, representing an ancestral type of this family. We overexpressed Omp85Tt in T. thermophilus and purified it from the native outer membranes. In the presence of detergent, purified Omp85Tt existed mainly as a monomer, composed of two stable protease-resistant modules. Circular dichroism spectroscopy indicated predominantly β-sheet secondary structure. Electron microscopy of negatively stained lipid-embedded Omp85Tt revealed ring-like structures with a central cavity of ∼1.5 nm in diameter. Single-channel conductance recordings indicated that Omp85Tt forms ion channels with two different conducting states, characterized by conductances of ∼0.4 nS and ∼0.65 nS, respectively. PMID:18456816

  11. Omp85(Tt) from Thermus thermophilus HB27: an ancestral type of the Omp85 protein family.

    PubMed

    Nesper, Jutta; Brosig, Alexander; Ringler, Philippe; Patel, Geetika J; Müller, Shirley A; Kleinschmidt, Jörg H; Boos, Winfried; Diederichs, Kay; Welte, Wolfram

    2008-07-01

    Proteins belonging to the Omp85 family are involved in the assembly of beta-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 protein, Omp85(Tt), representing an ancestral type of this family. We overexpressed Omp85(Tt) in T. thermophilus and purified it from the native outer membranes. In the presence of detergent, purified Omp85(Tt) existed mainly as a monomer, composed of two stable protease-resistant modules. Circular dichroism spectroscopy indicated predominantly beta-sheet secondary structure. Electron microscopy of negatively stained lipid-embedded Omp85(Tt) revealed ring-like structures with a central cavity of approximately 1.5 nm in diameter. Single-channel conductance recordings indicated that Omp85(Tt) forms ion channels with two different conducting states, characterized by conductances of approximately 0.4 nS and approximately 0.65 nS, respectively.

  12. Paenibacillus larvae-Directed Bacteriophage HB10c2 and Its Application in American Foulbrood-Affected Honey Bee Larvae

    PubMed Central

    Beims, Hannes; Wittmann, Johannes; Bunk, Boyke; Spröer, Cathrin; Rohde, Christine; Günther, Gabi; Rohde, Manfred; von der Ohe, Werner

    2015-01-01

    Paenibacillus larvae is the causative agent of American foulbrood (AFB), the most serious honey bee brood bacterial disease. We isolated and characterized P. larvae-directed bacteriophages and developed criteria for safe phage therapy. Whole-genome analysis of a highly lytic virus of the family Siphoviridae (HB10c2) provided a detailed safety profile and uncovered its lysogenic nature and a putative beta-lactamase-like protein. To rate its antagonistic activity against the pathogens targeted and to specify potentially harmful effects on the bee population and the environment, P. larvae genotypes ERIC I to IV, representatives of the bee gut microbiota, and a broad panel of members of the order Bacillales were analyzed for phage HB10c2-induced lysis. Breeding assays with infected bee larvae revealed that the in vitro phage activity observed was not predictive of the real-life scenario and therapeutic efficacy. On the basis of the disclosed P. larvae-bacteriophage coevolution, we discuss the future prospects of AFB phage therapy. PMID:26048941

  13. [Age and sex variations of HbA(1C) in a French population without known diabetes aged 6 to 79 years].

    PubMed

    Gusto, Gaëlle; Vol, Sylviane; Born, Catherine; Balkau, Beverley; Lamy, Jocelyne; Bourderioux, Christiane; Lantieri, Olivier; Tichet, Jean

    2011-01-01

    HbA(1C) is being used for screening and diagnosing diabetes. We determined mean values of HbA(1C) according to age and sex in a large population without known diabetes, in a wide age range 6-79  years. 5,138 men and women without known diabetes aged 6-79  years participated in a routine health examination provided by their medical insurance. HbA(1C) was assessed on an HPLC analyzer aligned with a DCCT method. HbA(1C) was approximately normally distributed in both men and women. Mean (SD) HbA(1C) were, for men vs women, in percentages 5.3 (0.4) vs 5.2 (0.3), in mmol/mol 34 (5) vs 34 (4) and in estimated blood glucose in mmol/L 5.83 (0.67) vs 5.75 (0.53). HbA(1C) increased with age by 0.08% every 10  years and this was attenuated to a 0.04% increase after adjustment on fasting plasma glucose. Between 15 and 49  years, women had lower values than men (p < 0.0001), but no sex differences were observed before and after this age range. In our population, 0.6% had HbA(1C) greater or equal to 6.5% and 88% (96% of men and 73% of women) of them had fasting plasma glucose greater or equal to 6,1 mmol/L. Threshold of 6.0% selected 2.8% of our population.

  14. Morphological and physiological study of the cardiac NOS/NO system in the Antarctic (Hb-/Mb-) icefish Chaenocephalus aceratus and in the red-blooded Trematomus bernacchii.

    PubMed

    Garofalo, Filippo; Amelio, Daniela; Cerra, Maria C; Tota, Bruno; Sidell, Bruce D; Pellegrino, Daniela

    2009-03-01

    The nitric oxide synthase (NOS)/nitric oxide (NO) system integrates cellular biochemical machinery and energetics. In heart microenvironment, dynamic NO behaviour depends upon the presence of superoxide anions, haemoglobin (Hb), and myoglobin (Mb), being hemoproteins are major players disarming NO bioactivity. The Antarctic icefish, which lack Hb and, in some species, also cardiac Mb, represent a unique model for exploring Hb and Mb impact on NOS/NO function. We report in the (Hb(-)/Mb(-)) icefish Chaenocephalus aceratus the presence of cardiac NOSs activity (NADPH-diaphorase) and endothelial NOS (eNOS)/inducible NOS (iNOS) zonal immuno-localization in the myocardium. eNOS is localized on endocardium and, to a lesser extent, in myocardiocytes, while iNOS is localized exclusively in myocardiocytes. Confronting eNOS and iNOS expression in Trematomus bernacchii (Hb(+)/Mb(+)), C. hamatus (Hb(-)/Mb(+)) and C. aceratus (Hb(-)/Mb(-)) is evident a lower expression in the Mb-less icefish. NO signaling was analyzed using isolated working heart preparations. In T. bernacchii, L-arginine and exogenous (SIN-1) NO donor dose-dependently decreased stroke volume, indicating decreased inotropism. L-arginine-induced inotropism was NOSs-dependent, being abolished by NOSs-inhibitor NG-monomethyl-L-arginine (L-NMMA). A SIN-1-induced negative inotropism was found in presence of SOD. NOS inhibition by L-N5-N-iminoethyl-L-ornithine (L-NIO) and L-NMMA confirmed the NO-mediated negative inotropic influence on cardiac performance. In contrast, in C. aceratus, L-arginine elicited a positive inotropism. SIN-1 induced a negative inotropism, which disappeared in presence of SOD, indicating peroxynitrite involvement. Cardiac performance was unaffected by L-NIO and L-NIL. NO signaling acted via a cGMP-independent mechanism. This high conservation degree of NOS localization pattern and signaling highlights its importance for cardiac biology.

  15. Cloning and characterization of HbMT2a, a metallothionein gene from Hevea brasiliensis Muell. Arg differently responds to abiotic stress and heavy metals.

    PubMed

    Li, Yan; Chen, Yue Yi; Yang, Shu Guang; Tian, Wei Min

    2015-05-22

    Metallothioneins (MTs) are of low molecular mass, cysteine-rich proteins. They play an important role in the detoxification of heavy metals and homeostasis of intracellular metal ions, and protecting against intracellular oxidative damages. In this study a full-length cDNA of type 2 plant metallothioneins, HbMT2a, was isolated from 25 mM Polyethyleneglycol (PEG) stressed leaves of Hevea brasiliensis by RACE. The HbMT2a was 372bp in length and had a 237bp open reading frame (ORF) encoding for a protein of 78 amino acid residues with molecular mass of 7.772 kDa. The expression of HbMT2a in the detached leaves of rubber tree clone RY7-33-97 was up-regulated by Me-JA, ABA, PEG, H2O2, Cu(2+) and Zn(2+), but down-regulated by water. The role of HbMT2a protein in protecting against metal toxicity was demonstrated in vitro. PET-28a-HbMT2-beared Escherichia coli. Differential expression of HbMT2a upon treatment with 10 °C was observed in the detached leaves of rubber tree clone 93-114 which is cold-resistant and Reken501 which is cold-sensitive. The expression patterns of HbMT2a in the two rubber tree clones may be ascribed to a change in the level of endogenous H2O2.

  16. Hb Bronte or alpha93(FG5)Val-->Gly: a new unstable variant of the alpha2-globin gene, associated with a mild alpha(+)-thalassemia phenotype.

    PubMed

    Lacerra, Giuseppina; Testa, Rosario; De Angioletti, Maria; Schilirò, Gino; Carestia, Clementina

    2003-08-01

    We report a new unstable variant identified in three carriers of a family from East Sicily; it was named Hb Bronte after the place from which the family originated. DNA sequencing from nucleotides -181 to +894 (alpha1) and to +884 (alpha2) revealed a GTG-->GGG substitution at codon 93 of the alpha2-globin gene. The MCV and MCH values were at the lower end of the normal range in the carriers. On cation exchange high performance liquid chromatography (HPLC), the Hb A2 level was apparently increased to around 6%, and a small abnormal peak (0.3-0.4%) was detected after Hb A2. Two abnormal bands were detected by cellulose acetate electrophoresis: a major band (about 3-4%) migrated between Hb A and Hb F; a minor band (<1%) migrated between Hb A2 and carbonic anhydrase. Normal values of Hb A2 were detected by DEAE microchromatography. On reversed phase HPLC the variant chain was not detected, and most likely it was eluted with the alpha chain peak. The isopropanol stability test was very slightly positive in the carriers. Hemolytic symptoms were absent with the exception of indirect bilirubin, which was at high borderline in 2/3 carriers. In biosynthesis in vitro, the specific activity of the alpha chains was much higher than that of the beta-globin chains, and the alpha/beta biosynthetic ratio in the mother and proband was of the beta-thalassemia (thal) type (2.24 and 2.54, respectively). Time course experiments showed that the increase of the 3H-specific activity of the peak containing normal and variant alpha chains was not linear and was much higher than that of beta chains; moreover, the alpha/beta biosynthetic ratio varied during the 2 hours incubation.

  17. Heparin-Binding EGF-like Growth Factor (HB-EGF) Decreases Inflammatory Cytokine Expression after Intestinal Ischemia/Reperfusion Injury

    PubMed Central

    Rocourt, Dorothy V.; Mehta, Veela B.; Besner, Gail E.

    2007-01-01

    Background Intestinal ischemia/reperfusion (I/R) injury is believed to be the major initiator of the systemic inflammatory response syndrome. As a result of intestinal I/R, the gut becomes a major source of inflammatory cytokine production. We have previously shown that HB-EGF is cytoprotective after intestinal I/R and down regulates pro-inflammatory cytokine production in vitro. We now examine the effects of HB-EGF on pro-inflammatory cytokine expression in vivo. Materials and Methods Rats were randomized into 3 groups: sham operated, superior mesenteric artery occlusion (SMAO) for 90 min followed by 8 hours of reperfusion (I/R), and I/R with intraluminal administration of HB-EGF 25 min after the initiation of ischemia (I/R+HB-EGF). Serum was drawn at 2, 4, 6, and 8 hours post reperfusion for determination of cytokine protein levels using a bioplex suspension array system. Additional animals underwent the same ischemic protocol followed by 30 and 60 min of reperfusion with harvesting of ileal mucosa. Ileal pro-inflammatory cytokine gene expression was determined using reverse transcriptase polymerase chain reaction (RT-PCR) with primers specific for TNF-α, IL-6 and IL-1β. Results HB-EGF decreased TNF-α, IL-6, and IL-1β serum protein levels at 4, 6 and 8 h after intestinal I/R injury. In addition, HB-EGF decreased local intestinal mucosal mRNA expression of TNF-α, IL-6, and IL-1β 30 and 60 min after intestinal injury. Conclusions We conclude that pro-inflammatory cytokine expression is increased both locally and in the systemic circulation after intestinal I/R and that the administration of HB-EGF significantly reduces intestinal I/R-induced pro-inflammatory cytokine expression in vivo. PMID:17291530

  18. Changes in HbA1c, body weight, and systolic blood pressure in type 2 diabetes patients initiating dapagliflozin therapy: a primary care database study

    PubMed Central

    Scheerer, Markus F; Rist, Roland; Proske, Orm; Meng, Annika; Kostev, Karel

    2016-01-01

    Aims To investigate changes in glycated hemoglobin (HbA1c), body weight (BW), and systolic blood pressure (SBP) in type 2 diabetes (T2D) primary care patients initiating dapagliflozin treatment. Methods T2D patients who started dapagliflozin in 985 general and 32 diabetologist practices (Disease Analyzer, Germany: December 2012–October 2014) were analyzed (3- and 6-month follow-up). Multivariate linear regression analyses were used to identify clinical characteristics and comorbidity associated with changes in HbA1c, BW, and SBP. Results The study included 1,169 T2D patients (age: 62.5 years; men: 59.3%; diabetologist care: 23%) with newly initiated dapagliflozin therapy. At the 3-month stage, dapagliflozin significantly reduced HbA1c (−0.8%±1.4%) compared to the baseline (8.5%±1.5%) (P<0.001). Changes were maintained after 6 months (−0.8%±1.5%) (P<0.001). Patients with high baseline HbA1c values (>9%) showed greater reductions in HbA1c than the overall sample (3 months −1.8%, 6 months −1.8%; both P<0.05). BW and SBP also showed statistically significant reductions with dapagliflozin over 3 and 6 months (−2.2 kg, P<0.001; −2.2 mmHg, P=0.003 and −2.5 kg, P<0.001; −2.3 mmHg, P=0.011, respectively). After 3 months, 53% of patients achieved a reduction in both HbA1c and BW; the same holds true for 45% of patients at the 6-month mark. Similar results were observed both in general and diabetologist practices. In multivariate analyses, baseline HbA1c (parameter estimate: −0.6479) and diabetologist care (−0.2553) were independent predictors of HbA1c change (6 months) (all P<0.05). Conclusion T2D patients treated with dapagliflozin therapy achieved statistically significant reductions in HbA1c, BW, and SBP in a real-world primary and diabetologist care setting. The changes were comparable to the results of the dapagliflozin clinical trial program. PMID:27822077

  19. A new approach for the carbon monoxide (CO) exposure diagnosis: measurement of total CO in human blood versus carboxyhemoglobin (HbCO).

    PubMed

    Varlet, Vincent; De Croutte, Emma Lagroy; Augsburger, Marc; Mangin, Patrice

    2013-07-01

    The aim of the study is to present the application of a headspace-gas chromatography-mass spectrometry (HS-GC-MS) method for the determination of the carbon monoxide (CO) blood concentration and to compare it with carboxyhemoglobin (HbCO) saturation. In postmortem cases, the HbCO measured by spectrophotometry frequently leads to inaccurate results due to inadequate samples or analyses. The true role of CO intoxication in the death of a person could be misclassified. The estimation of HbCO from HS-GC-MS CO measurements provides helpful information by determining the total CO levels (CO linked to hemoglobin (HbCO) and CO dissociated from hemoglobin). The CO concentrations were converted in HbCO saturation levels to define cutoff blood CO values. CO limits were defined as less than 1 μmol/mL for living persons, less than 1.5 μmol/mL for dead persons without CO exposure, and greater than 3 μmol/mL for dead persons with clear CO poisoning.

  20. A semi-mechanistic model of the relationship between average glucose and HbA1c in healthy and diabetic subjects.

    PubMed

    Lledó-García, Rocío; Mazer, Norman A; Karlsson, Mats O

    2013-04-01

    HbA1c is the most commonly used biomarker for the adequacy of glycemic management in diabetic patients and a surrogate endpoint for anti-diabetic drug approval. In spite of an empirical description for the relationship between average glucose (AG) and HbA1c concentrations, obtained from the A1c-derived average glucose (ADAG) study by Nathan et al., a model for the non-steady-state relationship is still lacking. Using data from the ADAG study, we here develop such models that utilize literature information on (patho)physiological processes and assay characteristics. The model incorporates the red blood cell (RBC) aging description, and uses prior values of the glycosylation rate constant (KG), mean RBC life-span (LS) and mean RBC precursor LS obtained from the literature. Different hypothesis were tested to explain the observed non-proportional relationship between AG and HbA1c. Both an inverse dependence of LS on AG and a non-specificity of the National Glycohemoglobin Standardization Program assay used could well describe the data. Both explanations have mechanistic support and could be incorporated, alone or in combination, in models allowing prediction of the time-course of HbA1c changes associated with changes in AG from, for example dietary or therapeutic interventions, and vice versa, to infer changes in AG from observed changes in HbA1c. The selection between the alternative mechanistic models require gathering of new information.

  1. Over-expression of a cytosolic isoform of the HbCuZnSOD gene in Hevea brasiliensis changes its response to a water deficit.

    PubMed

    Leclercq, J; Martin, F; Sanier, C; Clément-Vidal, A; Fabre, D; Oliver, G; Lardet, L; Ayar, A; Peyramard, M; Montoro, P

    2012-10-01

    Hevea brasiliensis is the main commercial source of natural rubber. Reactive oxygen species (ROS) scavenging systems are involved in various biotic and abiotic stresses. Genetic engineering was undertaken to study the strengthening of plant defences by antioxidants. To that end, Hevea transgenic plant lines over-expressing a Hevea brasiliensis cytosolic HbCuZnSOD gene were successfully established and regenerated. Over-expression of the HbCuZnSOD gene was not clearly related to an increase in SOD activity in plant leaves. The impact of HbCuZnSOD gene over-expression in somatic embryogenesis and in plant development are presented and discussed. The water deficit tolerance of two HbCuZnSOD over-expressing lines was evaluated. The physiological parameters of transgenic plantlets subjected to a water deficit suggested that plants from line TS4T8An displayed lower stomatal conductance and a higher proline content. Over-expression of the HbCuZnSOD gene and activation of all ROS-scavenging enzymes also suggested that protection against ROS was more efficient in the TS4T8An transgenic line.

  2. Cloning and Expression Analysis of One Gamma-Glutamylcysteine Synthetase Gene (Hbγ-ECS1) in Latex Production in Hevea brasiliensis.

    PubMed

    Fang, Wei; Qiao, Luo Shi; Ming, Wu; Jian, Qiu; Feng, Yang Wen; Hua, Gao Hong; Zhou, Xiao Xian

    2016-01-01

    Rubber tree is a major commercial source of natural rubber. Latex coagulation is delayed by thiols, which belong to the important type of antioxidants in laticifer submembrane, and is composed of glutathione (GSH), cysteine, and methionine. The rate-limiting enzyme, γ-ECS, plays an important role in regulating the biosynthesis of glutathione under any environment conditions. To understand the relation between γ-ECS and thiols and to correlate latex flow with one-time tapping and continuous tapping, we cloned and derived the full length of one γ-ECS from rubber tree latex (Hbγ-ECS1). According to qPCR analysis, the expression levels of Hbγ-ECS1 were induced by tapping and Ethrel stimulation, and the expression was related to thiols content in the latex. Continuous tapping induced injury, and the expression of HbγECS1 increased with routine tapping and Ethrel-stimulation tapping (more intensive tapping). According to expression in long-term flowing latex, the gene was related to the duration of latex flow. HbγECS1 was expressed in E. coli Rosetta using pET-sumo as an expression vector and the recombinant enzyme was purified; then we achieved 0.827 U/mg specific activity and about 66 kDa molecular weight. The present study can help us understand the complex role of Hbγ-ECS in thiols biosynthesis, which is influenced by tapping.

  3. Interaction between Mean Arterial Pressure and HbA1c in Prediction of Cardiovascular Disease Hospitalisation: A Population-Based Case-Control Study

    PubMed Central

    Yu, Dahai; Zhao, Zhanzheng; Simmons, David

    2016-01-01

    Objective. To explore the relationship between mean arterial pressure (MAP), HbA1c, and cardiovascular (CV) hospitalisation risk in type 2 diabetes. Design. Population-based case-control study. Settings. Primary and secondary care level in Cambridgeshire, United Kingdom. Participants. 588 patients with type 2 diabetes from 18 English general practices recording a CV hospitalisation in 2009–2011 were included. Risk-set sampling was used to select 2920 gender, age, and practice matched control type 2 diabetes patients. Main Outcome Measure. Conditional logistic regression was used to explore further dose-response relationships between MAP, HbA1c, and CV hospitalisation risk. Results. The relationship between MAP and CV hospitalisation was nonlinear (P < 0.001 for linearity test). The MAP associated with the lowest CV hospitalisation risk was 97 (95% CI: 93–101) mmHg. An interaction between MAP and HbA1c for increased risk of cardiovascular hospitalisation was observed among those with HbA1c < 7% (53 mmol/mol) and MAP < 97 mmHg. Conclusions. In type 2 diabetes, MAP is a good predictor of CV hospitalisation risk. CV hospitalisation is lowest with a MAP between 93 and 101 mmHg. CV hospitalisation was particularly high among those with both a low MAP and a lower HbA1c. PMID:27382575

  4. Cloning and Expression Analysis of One Gamma-Glutamylcysteine Synthetase Gene (Hbγ-ECS1) in Latex Production in Hevea brasiliensis

    PubMed Central

    Fang, Wei; Qiao, Luo Shi; Ming, Wu; Jian, Qiu; Feng, Yang Wen; Hua, Gao Hong; Zhou, Xiao Xian

    2016-01-01

    Rubber tree is a major commercial source of natural rubber. Latex coagulation is delayed by thiols, which belong to the important type of antioxidants in laticifer submembrane, and is composed of glutathione (GSH), cysteine, and methionine. The rate-limiting enzyme, γ-ECS, plays an important role in regulating the biosynthesis of glutathione under any environment conditions. To understand the relation between γ-ECS and thiols and to correlate latex flow with one-time tapping and continuous tapping, we cloned and derived the full length of one γ-ECS from rubber tree latex (Hbγ-ECS1). According to qPCR analysis, the expression levels of Hbγ-ECS1 were induced by tapping and Ethrel stimulation, and the expression was related to thiols content in the latex. Continuous tapping induced injury, and the expression of HbγECS1 increased with routine tapping and Ethrel-stimulation tapping (more intensive tapping). According to expression in long-term flowing latex, the gene was related to the duration of latex flow. HbγECS1 was expressed in E. coli Rosetta using pET-sumo as an expression vector and the recombinant enzyme was purified; then we achieved 0.827 U/mg specific activity and about 66 kDa molecular weight. The present study can help us understand the complex role of Hbγ-ECS in thiols biosynthesis, which is influenced by tapping. PMID:27419133

  5. Are the Same Clinical Risk Factors Relevant for Incident Diabetes Defined by Treatment, Fasting Plasma Glucose, and HbA1c?

    PubMed Central

    Balkau, Beverley; Soulimane, Soraya; Lange, Céline; Gautier, Alain; Tichet, Jean; Vol, Sylviane

    2011-01-01

    OBJECTIVE To compare incidences and risk factors for diabetes using seven definitions, with combinations of pharmacological treatment, fasting plasma glucose (FPG) ≥7.0 mmol/L, and HbA1c ≥6.5%. RESEARCH DESIGN AND METHODS Participants aged 30–65 years from the Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) cohort were followed for 9 years. RESULTS More men had incident diabetes as defined by FPG ≥7.0 mmol/L and/or treatment than by HbA1c ≥6.5% and/or treatment: 7.5% (140/1,867) and 5.3% (99/1,874), respectively (P < 0.009); for women incidences were similar: 3.2% (63/1,958) and 3.4% (66/1,954). Known risk factors predicted diabetes for almost all definitions. Among those with incident diabetes by FPG alone versus HbA1c alone, there were more men (78 vs. 35%), case patients were 8 years younger, and fewer were alcohol abstainers (12 vs. 35%) (all P < 0.005). A diabetes risk score discriminated well between those with and without incident diabetes for all definitions. CONCLUSIONS In men, FPG definitions yielded more incident cases of diabetes than HbA1c definitions, in contrast with women. An FPG-derived risk score remained relevant for HbA1c-defined diabetes. PMID:21346181

  6. Rapid Induction of Apoptosis in Gastrulating Mouse Embryos by Ethanol and Its Prevention by HB-EGF

    PubMed Central

    Kilburn, Brian A.; Chiang, Po Jen; Wang, Jun; Flentke, George R.; Smith, Susan M.; Armant, D. Randall

    2006-01-01

    Background Ethanol exposure during gastrulation and early neurulation induces apoptosis within certain embryonic cell populations, leading to craniofacial and neurological defects. There is currently little information about the initial kinetics of ethanol-induced apoptosis, and interest in the ability of endogenous survival factors to moderate apoptosis is growing. Ethanol alters intracellular signaling, leading to cell death in chick embryos, suggesting that apoptosis could occur rapidly and that signaling pathways activated by survival factors might reduce apoptosis. Methods Pregnant mice were intubated with 1, 2, or 4 g/kg ethanol on day 7.5 of embryogenesis (E7.5) 1, 3, or 6, hours before harvesting gastrulation-stage embryos. Control animals received maltose/dextran. Blood alcohol concentrations (BAC) were determined by gas chromatography. E7.5 embryos isolated from untreated dams were cultured in vitro for 1 or 3 hr with 0 or 400 mg% ethanol and 0 or 5 nM heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF). Apoptosis was quantified using fluorescence microscopy to detect annexin V binding and DNA fragmentation [terminal deoxynucleotidyl transferase-mediated dUTP-X nick end labeling (TUNEL)] in whole-mount or sectioned embryos. Results Both annexin V binding and TUNEL were elevated (p<0.05) in embryos exposed in utero to 1 g/kg ethanol for 3 hours, increasing linearly with time and ethanol concentration. Apoptosis increased (p<0.05) in all germ cell layers. Mice treated with 4 g/kg sustained BAC of 400 mg% for nearly 3 hours, significantly increasing apoptosis within the first hour. Cultured embryos exposed to 400 mg% ethanol displayed 2- to 3-fold more TUNEL than vehicle-treated embryos (p<0.05); however, exogenous HB-EGF prevented apoptosis. Conclusions Ethanol rapidly produced apoptosis in gastrulation-stage embryos, consistent with induction by intracellular signaling. The ethanol-induced apoptotic pathway was blocked by the

  7. Control of human endometrial stromal cell motility by PDGF-BB, HB-EGF and trophoblast-secreted factors.

    PubMed

    Schwenke, Maren; Knöfler, Martin; Velicky, Philipp; Weimar, Charlotte H E; Kruse, Michelle; Samalecos, Annemarie; Wolf, Anja; Macklon, Nick S; Bamberger, Ana-Maria; Gellersen, Birgit

    2013-01-01

    Human implantation involves extensive tissue remodeling at the fetal-maternal interface. It is becoming increasingly evident that not only trophoblast, but also decidualizing endometrial stromal cells are inherently motile and invasive, and likely contribute to the highly dynamic processes at the implantation site. The present study was undertaken to further characterize the mechanisms involved in the regulation of endometrial stromal cell motility and to identify trophoblast-derived factors that modulate migration. Among local growth factors known to be present at the time of implantation, heparin-binding epidermal growth factor-like growth factor (HB-EGF) triggered chemotaxis (directed locomotion), whereas platelet-derived growth factor (PDGF)-BB elicited both chemotaxis and chemokinesis (non-directed locomotion) of endometrial stromal cells. Supernatants of the trophoblast cell line AC-1M88 and of first trimester villous explant cultures stimulated chemotaxis but not chemokinesis. Proteome profiling for cytokines and angiogenesis factors revealed neither PDGF-BB nor HB-EGF in conditioned media from trophoblast cells or villous explants, while placental growth factor, vascular endothelial growth factor and PDGF-AA were identified as prominent secretory products. Among these, only PDGF-AA triggered endometrial stromal cell chemotaxis. Neutralization of PDGF-AA in trophoblast conditioned media, however, did not diminish chemoattractant activity, suggesting the presence of additional trophoblast-derived chemotactic factors. Pathway inhibitor studies revealed ERK1/2, PI3 kinase/Akt and p38 signaling as relevant for chemotactic motility, whereas chemokinesis depended primarily on PI3 kinase/Akt activation. Both chemotaxis and chemokinesis were stimulated upon inhibition of Rho-associated, coiled-coil containing protein kinase. The chemotactic response to trophoblast secretions was not blunted by inhibition of isolated signaling cascades, indicating activation of

  8. Occurrence of Transsulfuration in Synthesis of l-Homocysteine in an Extremely Thermophilic Bacterium, Thermus thermophilus HB8

    PubMed Central

    Yamagata, Shuzo; Ichioka, Kazuhito; Goto, Koji; Mizuno, Yasuko; Iwama, Tomonori

    2001-01-01

    A cell extract of an extremely thermophilic bacterium, Thermus thermophilus HB8, cultured in a synthetic medium catalyzed cystathionine γ-synthesis with O-acetyl-l-homoserine and l-cysteine as substrates but not β-synthesis with dl-homocysteine and l-serine (or O-acetyl-l-serine). The amounts of synthesized enzymes metabolizing sulfur-containing amino acids were estimated by determining their catalytic activities in cell extracts. The syntheses of cysthathionine β-lyase (EC 4.4.1.8) and O-acetyl-l-serine sulfhydrylase (EC 4.2.99.8) were markedly repressed by l-methionine supplemented to the medium. l-Cysteine and glutathione, both at 0.5 mM, added to the medium as the sole sulfur source repressed the synthesis of O-acetylserine sulfhydrylase by 55 and 73%, respectively, confirming that this enzyme functions as a cysteine synthase. Methionine employed at 1 to 5 mM in the same way derepressed the synthesis of O-acetylserine sulfhydrylase 2.1- to 2.5-fold. A method for assaying a low concentration of sulfide (0.01 to 0.05 mM) liberated from homocysteine by determining cysteine synthesized with it in the presence of excess amounts of O-acetylserine and a purified preparation of the sulfhydrylase was established. The extract of cells catalyzed the homocysteine γ-lyase reaction, with a specific activity of 5 to 7 nmol/min/mg of protein, but not the methionine γ-lyase reaction. These results suggested that cysteine was also synthesized under the conditions employed by the catalysis of O-acetylserine sulfhydrylase using sulfur of homocysteine derived from methionine. Methionine inhibited O-acetylserine sulfhydrylase markedly. The effects of sulfur sources added to the medium on the synthesis of O-acetylhomoserine sulfhydrylase and the inhibition of the enzyme activity by methionine were mostly understood by assuming that the organism has two proteins having O-acetylhomoserine sulfhydrylase activity, one of which is cystathionine γ-synthase. Although it has been

  9. Ultrafast heme-ligand recombination in truncated hemoglobin HbO from Mycobacterium tuberculosis: A ligand cage

    NASA Astrophysics Data System (ADS)

    Jasaitis, Audrius; Ouellet, Hugues; Lambry, Jean-Christophe; Martin, Jean-Louis; Friedman, Joel M.; Guertin, Michel; Vos, Marten H.

    2012-03-01

    Truncated hemoglobin HbO from Mycobacterium tuberculosis displays very slow exchange of diatomic ligands with its environment. Using femtosecond spectroscopy, we show that upon photoexcitation, ligands rebind with unusual speed and efficiency. Only ˜1% O2 can escape from the heme pocket and less than 1% NO. Most remarkably, CO rebinding occurs for 95%, predominantly in 1.2 ns. The general CO rebinding properties are unexpectedly robust against changes in the interactions with close by aromatic residues Trp88 (G8) and Tyr36 (CD1). Molecular dynamics simulations of the CO complex suggest that interactions of the ligand with structural water molecules as well as its rotational freedom play a role in the high reactivity of the ligand and the heme. The slow exchange of ligands between heme and environment may result from a combination of hindered ligand access to the heme pocket by the network of distal aromatic residues, and low escape probability from the pocket.

  10. Adsorption of Two Dyes by Mg(OH)2: Procion Blue HB and Remazol Brilliant Blue R

    NASA Astrophysics Data System (ADS)

    Bouberka, Zohra; Bentaleb, Kahina; Benabbou, Khalil A.; Maschke, Ulrich

    The use of low-cost and ecofriendly adsorbents has been investigated as an ideal alternative to the current expensive methods of removing dyes from wastewater. Mg(OH)2 sludge was produced from precipitation of magnesium ions (Mg2+) with NaOH in pH = 10 and investigated as a low-cost adsorbent. This paper deals with the removal of textile dyes from aqueous solutions by Mg(OH)2. Reactive Procion blue HB (PR) and Acid Remazol brilliant blue R (RB) were used as model compounds. The adsorption capacity was found as 43.47 and 26.89 mg/g at initial pH 6.5.

  11. Novel epoxy-silicone thermolytic transparent packaging adhesives chemical modified by ZnO nanowires for HB LEDs

    NASA Astrophysics Data System (ADS)

    He, Ying; Wang, Jun-An; Pei, Chang-Long; Song, Ji-Zhong; Zhu, Di; Chen, Jie

    2010-10-01

    A novel high transparent thermolytic epoxy-silicone for high-brightness light-emitting diode (HB-LED) is introduced, which was synthesized by polymerization using silicone matrix via diglycidyl ether bisphenol-A epoxy resin (DGEBA) as reinforcing agent, and filling ZnO nanowires to modify thermal conductivity and control refractive index of the hybrid material. The interactions of ZnO nanowires with polymers are mediated by the ligands attached to the nanoparticles. Thus, the ligands markedly influence the properties of ZnO nanowires/epoxy-silicone composites. The refractive indices of the prepared hybrid adhesives can be tuned by the ZnO nanowires from 1.4711 to 1.5605. Light transmittance can be increased by 20% from 80 to 95%. The thermal conductivity of the transparent packaging adhesives is 0.89-0.90 W/mK.

  12. Investigation Of In-Line Monitoring Options At H Canyon/HB Line For Plutonium Oxide Production

    SciTech Connect

    Sexton, L.

    2015-10-14

    H Canyon and HB Line have a production goal of 1 MT per year of plutonium oxide feedstock for the MOX facility by FY17 (AFS-2 mission). In order to meet this goal, steps will need to be taken to improve processing efficiency. One concept for achieving this goal is to implement in-line process monitoring at key measurement points within the facilities. In-line monitoring during operations has the potential to increase throughput and efficiency while reducing costs associated with laboratory sample analysis. In the work reported here, we mapped the plutonium oxide process, identified key measurement points, investigated alternate technologies that could be used for in-line analysis, and initiated a throughput benefit analysis.

  13. A new alpha-globin variant with increased oxygen affinity in a Swiss family: Hb Frauenfeld [alpha 138(H21)Ser-->Phe, TCC>TTC (alpha 2)].

    PubMed

    Hochuli, Michel; Zurbriggen, Karin; Schmid, Marlis; Speer, Oliver; Rochat, Philippe; Frauchiger, Beat; Kleinert, Peter; Schmugge, Markus; Troxler, Heinz

    2009-01-01

    A new alpha-globin mutation [alpha 138(H21)Ser-->Phe] was found in a 55-year-old male proband with an erythrocytosis known since his youth. Cation exchange high performance liquid chromatography (HPLC) revealed an additional peak eluting slightly before Hb A indicating the presence of a variant. The peak area of the variant was approximately one-third that of Hb A suggesting an alpha-globin variant. Matrix-assisted laser desorption ionization-time-of-flight mass spectrometry analysis confirmed the mutation at the protein level. The variant is also detectable with isoelectric focusing and reversed phase HPLC. DNA analysis revealed a heterozygous sequence mutation at codon 138 of the alpha2 gene. A C>T transition at the second nucleotide of the codon indicated a Ser-->Phe exchange. The variant showed increased oxygen affinity and was named Hb Frauenfeld.

  14. [Attempt to estimate risks of fatal poisoning on the basis of HCN and HbCO concentrations in blood of fire victims].

    PubMed

    Grabowska, Teresa; Sybirska, Halina; Maliński, Marian

    2003-01-01

    Using the results of HCN and HbCO concentrations in the blood of 174 deceased found in different burning spaces and 35 people with symptoms of poisoning evacuated from the scene of a fire and then admitted to hospital. The correlation between blood concentration of both these xenobiotics and death or chance of survival in a fire was estimated by statistical analysis. An attempt was made to define a value of so-called "cut-off" points for HbCO and HCN by independence test chi 2 with Yates's correction. Point and interval estimations (95% Comfield's confidence interval) were used for the odds ratio (OR). The research showed that there was a strict statistical correlation between the chance of survival and death risks dependent on blood concentrations of HCN and HbCO in all the groups examined.

  15. [Experimental hemorrhagic stroke: the effect of the peptide preparation cortexin in the formation of Hb-NO-complexes and other blood paramagnetic centers].

    PubMed

    Reutov, V P; Baĭder, L M; Kuropteva, Z V; Krushinskiĭ, A L; Kuzenkov, V S; Moldaliev, Zh T; Granstrem, O K

    2011-01-01

    Using electronic paramagnetic resonance (EPR), we studied the effect of the peptide cortexin on the content of hemoglobin nitrozyl complexes (Hb-NO-complexes) and other paramagnetic centers (transferrin, methemoglobin) in the blood of rats of Krushynsky-Molodkina line in the experimental hemorrhagic stroke induced by acoustic stress. After the acoustic exposure, the level of Hb-NO-complexes have increased by more than 6 times. The intensity of the EPR signal of the plasma peptide transferrin increased by 1,5 times. The level of blood methemoglobin was also elevated, though not significantly, after the acoustic stress. Cortexin substantially reduces the formation of Hb-NO-complexes and, therefore, the level of nitride oxide while the contents of transferrin and methemoglobin remain intact.

  16. Efficacy of Rapamycin as Inducer of Hb F in Primary Erythroid Cultures from Sickle Cell Disease and β-Thalassemia Patients.

    PubMed

    Pecoraro, Alice; Troia, Antonio; Calzolari, Roberta; Scazzone, Concetta; Rigano, Paolo; Martorana, Adriana; Sacco, Massimiliano; Maggio, Aurelio; Di Marzo, Rosalba

    2015-01-01

    Phenotypic improvement of hemoglobinopathies such as sickle cell disease and β-thalassemia (β-thal) has been shown in patients with high levels of Hb F. Among the drugs proposed to increase Hb F production, hydroxyurea (HU) is currently the only one proven to improve the clinical course of these diseases. However, Hb F increase and patient's response are highly variable, indicating that new pharmacological agents could be useful for patients not responding to HU or showing a reduction of response during long-term therapy. In this study we evaluated the efficacy of rapamycin, a lypophilic macrolide used for the prevention of acute rejection in renal transplant recipients, as an inducer of Hb F production. The analyses were performed in cultured erythroid progenitors from 25 sickle cell disease and 25 β-thal intermedia (β-TI) patients. The use of a quantitative Real-Time-polymerase chain reaction ReTi-PCR technique and high performance liquid chromatography (HPLC) allowed us to determine the increase in γ-globin mRNA expression and Hb F production in human erythroid cells treated with rapamycin. The results of our study demonstrated an increase in vitro of γ-globin mRNA expression in 15 sickle cell disease and 14 β-TI patients and a corresponding Hb F increase. The induction by rapamycin, even if lower or similar in most of samples analyzed, in some cases was higher than HU. These data suggest that rapamycin could be a good candidate to be used in vivo for the treatment of hemoglobinopathies.

  17. Sickle cell trait (HbAS) and stunting in children below two years of age in an area of high malaria transmission

    PubMed Central

    Kreuels, Benno; Ehrhardt, Stephan; Kreuzberg, Christina; Adjei, Samuel; Kobbe, Robin; Burchard, Gerd D; Ehmen, Christa; Ayim, Matilda; Adjei, Ohene; May, Jürgen

    2009-01-01

    Background While the protective effects of sickle cell trait (HbAS) against severe malaria and the resulting survival advantage are well known, the impact on the physical development in young children remains unclear. This study was aimed to investigate the relationship between HbS carriage and stunting in children below two years of age in a cohort from the Ashanti Region, Ghana. Methods 1,070 children were recruited at three months of age and followed-up for 21 months with anthropometric measurements performed every three months. Incidence rate ratios with 95% confidence intervals were calculated by Poisson regression to estimate the association of β-globin genotypes with the number of malaria episodes. Odds ratios (OR) were calculated for the association between the occurrence of β-globin genotypes and/or malaria episodes and stunting. The age-dependent between-group and within-group effects for the β-globin genotypes were assessed by population-averaged models estimated by generalized estimation equation with autoregressive correlation structure. Results Analyses showed a significantly lower age-dependent risk of stunting (OR 0.56; 95% CI 0.33–0.96) in carriers of the HbAS genotype (n = 102) in comparison to those with HbAA (n = 692). This effect was restricted to children who experienced malaria episodes during the observation period suggesting that the beneficial effect of the β-globin HbS variant on the incidence of stunting is closely linked to its protection from mild malaria episodes. Conclusion The lower risk of chronic malnutrition in early childhood, mediated by protection against mild malaria episodes, may contribute to the survival advantage of HbAS carriers in areas of high malaria transmission. PMID:19149873

  18. Transformation with TT8 and HB12 RNAi Constructs in Model Forage (Medicago sativa, Alfalfa) Affects Carbohydrate Structure and Metabolic Characteristics in Ruminant Livestock Systems.

    PubMed

    Li, Xinxin; Zhang, Yonggen; Hannoufa, Abdelali; Yu, Peiqiang

    2015-11-04

    Lignin, a phenylpropanoid polymer present in secondary cell walls, has a negative impact on feed digestibility. TT8 and HB12 genes were shown to have low expression levels in low-lignin tissues of alfalfa, but to date, there has been no study on the effect of down-regulation of these two genes in alfalfa on nutrient chemical profiles and availability in ruminant livestock systems. The objectives of this study were to investigate the effect of transformation of alfalfa with TT8 and HB12 RNAi constructs on carbohydrate (CHO) structure and CHO nutritive value in ruminant livestock systems. The results showed that transformation with TT8 and HB12 RNAi constructs reduced rumen, rapidly degraded CHO fractions (RDCA4, P = 0.06; RDCB1, P < 0.01) and totally degraded CHO fraction (TRDCHO, P = 0.08). Both HB12 and TT8 populations had significantly higher in vitro digestibility of neutral detergent fiber (NDF) at 30 h of incubation (ivNDF30) compared to the control (P < 0.01). The TT8 populations had highest ivDM30 and ivNDF240. Transformation of alfalfa with TT8 and HB12 RNAi constructs induced molecular structure changes. Different CHO functional groups had different sensitivities and different responses to the transformation. The CHO molecular structure changes induced by the transformation were associated with predicted CHO availability. Compared with HB12 RNAi, transformation with TT8 RNAi could improve forage quality by increasing the availability of both NDF and DM. Further study is needed on the relationship between the transformation-induced structure changes at a molecular level and nutrient utilization in ruminant livestock systems when lignification is much higher.

  19. Incidence of the Hb E [β26(B8)Glu→Lys, GAG>AAG] variant in Totos, one of the smallest primitive tribes in the world.

    PubMed

    Bhattacharyya, Deboshree; Mukhopadhyay, Ashis; Chakraborty, Abhijit; Dasgupta, Swati; Mukhopadhyay, Soma; Pal, Nabamita; Basak, Jayasri

    2013-01-01

    Toto is one of the smallest tribes in the world. This primitive sub Himalayan, endogamous tribe lives in a small, isolated village called Totopara in the Jalpaiguri district of West Bengal in India. The tribal communities of West Bengal are vulnerable to various genetic disorders such as β-thalassemia (β-thal). We have studied 443 Totos to define their Hb E [β26(B8)Glu→Lys, GAG>AAG] status. Awareness and screening camps have been organized in various parts of Totopara during the last 2 years. We collected 3 mL peripheral blood from each individual aseptically on which to use the naked eye single tube red cell osmotic fragility test (NESTROFT); complete hemogram and high performance liquid chromatography (HPLC) were done to detect their carrier status. The Hb E variant had been found to be prevalent among the Totos. To confirm the codon 26 (GAG>AAG) mutation in the β-globin gene, amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) was performed. Restriction fragment length polymorphism (RFLP)-PCR was carried out with 44 Hb E alleles to construct the haplotype(s) of the Totos. Our extensive studies have revealed that 49.21% of Totos are Hb E heterozygotes and 19.19% Totos are Hb E homozygotes. The most prevalent haplotype linked with the codon 26 mutation in the Totos is [+ - - - - -] (HincII 5'ϵ, HindIII (G)γ, HindIII (A)γ, HincII 5'ψβ, HincII 3'ψβ and HinfI 3'β). Consanguineous marriages have resulted in a significant increase of the percentages of heterozygotes and homozygotes of Hb E in the Totos. Genetic counseling is essential and important to prevent the spread of this mutation and hence to save them from having any kind of clinically significant hemoglobinopathy in the future.

  20. The effect of nano-curcumin on HbA1c, fasting blood glucose, and lipid profile in diabetic subjects: a randomized clinical trial

    PubMed Central

    Rahimi, Hamid Reza; Mohammadpour, Amir Hooshang; Dastani, Mostafa; Jaafari, Mahmoud Reza; Abnous, Khalil; Ghayour Mobarhan, Majid; Kazemi Oskuee, Reza

    2016-01-01

    Objective: Diabetes mellitus is defined as a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both or insulin resistance. Curcumin inhibits NF-κB signaling pathway. The aim of this study is evaluation of the effect of Nano-curcumin on HbA1C, fast blood glucose and lipid profile in diabetic patients. Materials and Methods: Seventy type-2 diabetic patients (fasting blood glucose (FBG) ≥ 126 mg/dL or 2-hr postprandial blood glucose ≥200 mg/dl) randomly receivedeither Curcumin (as nano-micelle 80 mg/day) or placebo for 3 months in a double blind randomized clinical trial. Fasting blood glucose, HbA1C, and lipids profile were checked before and after the intervention. Data analyses, including parametric and nonparametric tests were done using the SPSS 11.5 software. A p value < 0.05 was regarded as statistically significant. (RCT registration code: IRCT2013081114330N1) Results: Mean age, BMI, FBG, total cholesterol (TC), triglyceride (TG), LDL, HDL, HbA1c , and sex and had no significant difference at the baseline between the groups. In Nano-curcumin group, a significant decrease was found in HbA1C, FBG, TG, and BMI comparing results of each subject before and after the treatment (p<0.05). By comparing pre- and post-treatment values among the groups, HbA1c, eAG, LDL-C, and BMI variables showed significant differences (p<0.05). Conclusion: These findings suggest an HbA1c lowering effect for Nano-curcumin in type-2 diabetes; also, it is partially decrease in serum LDL-C and BMI. PMID:27761427

  1. Hb A2-Pasteur-Tunis [delta59(E3)Lys-->Asn, AAG-->AAC]: a new delta chain variant detected by DNA sequencing in a Tunisian carrier of the codon 39 (C-->T) beta0-Thalassemia mutation.

    PubMed

    Moumni, Imen; Zorai, Amine; Daoued, Bechir Ben; Mosbahi, Ikbel; Omar, Souheil; Kaabachi, Neziha; Dellagi, Koussay; Abbes, Salem

    2007-01-01

    We describe a new delta-globin variant, Hb A2-Pasteur-Tunis [delta59(E3)Lys-->Asn, AAG-->AAC]. This hemoglobin (Hb) displayed an electrophoretic mobility faster than normal Hb A2 and was expressed at 2.2 %. The molecular defect was characterized by DNA sequencing and confirmed by a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)-designed protocol. Hb A2-Pasteur-Tunis was found in a carrier of a codon 39 (C-->T) beta0-thalassemia (thal), presenting with a normal Hb A2 level. Phenotype and genotype investigations revealed that the total Hb A2 level of the patient was that expected for a minor beta-thal (4.8%).

  2. Description of the phenotypes of 63 heterozygous, homozygous and compound heterozygous patients carrying the Hb Groene Hart [α119(H2)Pro→Ser; HBA1: c.358C>T] variant.

    PubMed

    Joly, Philippe; Lacan, Philippe; Garcia, Caroline; Francina, Alain

    2014-01-01

    We here report the phenotypes and genotypes of 63 patients of North African origin, carriers of Hb Groene Hart [Hb GH, α119(H2)Pro → Ser; HBA1: c.358C>T], an α(+)-thalassemia (α(+)-thal) hemoglobin (Hb) variant. Fifty patients were heterozygous, five were homozygous and eight also carried the common -α(3.7) (rightward) deletion in compound heterozygosity. The expression of the α(GH)-globin chain is increased in the following order: heterozygous, compound heterozygous and homozygous. Parallel significant changes of mean corpuscular Hb (MCH) and mean corpuscular volume (MCV) were also observed. Our large cohort of Hb GH carriers could have been obtained by the systematic realization of globin chain separation by reversed phase liquid chromatography (RP-LC) in our routine Hb testing.

  3. HbA1c overtesting and overtreatment among US adults with controlled type 2 diabetes, 2001-13: observational population based study

    PubMed Central

    Van Houten, Holly K; Ross, Joseph S; Montori, Victor M; Shah, Nilay D

    2015-01-01

    Study question What is the extent and effect of excessive testing for glycated hemoglobin (HbA1c) among adults with controlled type 2 diabetes? Methods A retrospective analysis of data from a national administrative claims database included commercially insured individuals in the USA, 2001-13. Study patients were aged 18 years or older, had type 2 diabetes with stable glycemic control (two consecutive tests showing HbA1c<7.0% within 24 months), did not use insulin, had no history of severe hypoglycemia or hyperglycemia, and were not pregnant. HbA1c testing frequency was measured within 24 months after the second (index) HbA1c test, and classified as guideline recommended (≤2 times/year), frequent (3-4 times/year), and excessive (≥5 times/year). Changes in treatment regimen were ascertained within three months of the index test. Study answer and limitations Of 31 545 patients in the study cohort (mean age 58 years; mean index HbA1c 6.2%), HbA1c testing frequency was excessive in 6% and frequent in 55%. Despite good glycemic control at baseline, treatment was further intensified by addition of glucose lowering drugs or insulin in 8.4% of patients (comprising 13%, 9%, and 7% of those tested excessively, frequently, and per guidelines, respectively; P<0.001). Compared with guideline recommended testing, excessive testing was associated with treatment intensification (odds ratio 1.35 (95% confidence interval 1.22 to 1.50)). Excessive testing rates remained unchanged in 2001-08, but fell significantly after 2009. The odds of excessive testing was 46% lower in 2011 than in 2001-02. The study population is not representative of all US patients with type 2 diabetes because it was restricted to commercially insured adults with stable and controlled diabetes not receiving insulin treatment. The study design did not capture the underuse of HbA1c testing. What this study adds In this US cohort of adults with stable and controlled type 2 diabetes, more than 60% received

  4. ICSH recommendations for assessing automated high-performance liquid chromatography and capillary electrophoresis equipment for the quantitation of HbA2.

    PubMed

    Stephens, A D; Colah, R; Fucharoen, S; Hoyer, J; Keren, D; McFarlane, A; Perrett, D; Wild, B J

    2015-10-01

    Automated high performance liquid chromatography and Capillary electrophoresis are used to quantitate the proportion of Hemoglobin A2 (HbA2 ) in blood samples order to enable screening and diagnosis of carriers of β-thalassemia. Since there is only a very small difference in HbA2 levels between people who are carriers and people who are not carriers such analyses need to be both precise and accurate. This paper examines the different parameters of such equipment and discusses how they should be assessed.

  5. [Indicators of glycemic control --hemoglobin A1c (HbA1c), glycated albumin (GA), and 1,5-anhydroglucitol (1,5-AG)].

    PubMed

    Sato, Asako

    2014-01-01

    The clinical goal of diabetes management is a good quality of life that is not different from that of a healthy subjects. To fulfill the goal, prevention of complications is needed under good glycemic control. Although blood glucose measurement is essential for glycemic control, there are diurnal variations in blood glucose levels. An indicator of long-term glycemic control is necessary. HbA1c is the gold standard measurement for the assessment of glycemic control, and worldwide large scale clinical studies of diabetes complications have greatly valued HbA1c as an indicator of glycemic control. In addition, recently, HbA1c was recommended for use in the diagnosis of diabetes in Japan and in the United States. Although HbA1c is used widely and internationally, international standardization of the HbA1c value has not been achieved. In Japan, from April 2014, it has been decided to adopt the National Glycohemoglobin Standardization Program (NGSP) value, which is used by many countries globally, as the first step toward internationalization. Recently, cardiovascular disease in diabetic patients has been increasing in Japan. Relationships between postprandial hyperglycemia and cardiovascular disease have been noted. Therefore, the correction of postprandial hyperglycemia is one of the important goals of glycemic control to prevent cardiovascular disease. HbA1c or glycated albumin (GA) results from the glycation of hemoglobin or serum albumin and represents 2-month or 2-week glycemia, respectively. In addition, the glycation speed of GA is ten times faster than HbA1c, so GA is likely to reflect the variation in blood glucose and postprandial hyperglycemia in combination with HbA1c and its value. 1,5-anhydroglucitol (AG) is a marker of glycemia-induced glycosuria, since reabsorption of filtered 1,5-AG in the proximal tubule is competitively inhibited by glucose. It is an indicator to identify rapid changes in hyperglycemia. Understanding the characteristics of the

  6. An Elevated HbA1c Level Is Associated With Short-Term Adverse Outcomes in Patients With Gastrointestinal Cancer and Type 2 Diabetes Mellitus

    PubMed Central

    Huang, Yingchun; Zheng, Huazhen; Chen, Peicong; Yang, Jin; Lin, Shaomin; Liu, Tingting; Chen, Shanwei; Lu, Siqiang; Chen, Junlian; Chen, Wenpu; Peng, Nanhai

    2017-01-01

    Background Although an elevated hemoglobin A1c (HbAc1) level is an independent predictor of worse survival in patients with both digestive cancer and diabetes mellitus, its relationship to short-term prognosis in these patients has not been addressed. This study assessed this relationship in gastrointestinal cancer (GIC) patients with type 2 diabetes mellitus (T2DM). Methods A retrospective review of patients with GIC with or without T2DM from 2004 to 2014 was performed. Patients with T2DM were grouped according to HbA1c level, either normal (mean < 7.0%) or elevated (mean ≥ 7.0%). Age- and sex-matched GIC patients without T2DM served as controls. Results One hundred and eighteen patients aged 33 - 81 years with T2DM met the study eligibility criteria; 51 were in the normal HbA1c group, and 67 were in the elevated HbA1c group. The 91 patients in the non-T2DM group were randomly selected and matched to the T2DM group in terms of admittance date, age, and sex. There was a trend toward a higher 180-day mortality rate in the T2DM group compared with the non-T2DM group (15.3% vs. 7.7%, P = 0.095) and in the elevated HbA1c group compared with the normal HbA1c group (19.4% vs. 9.8%, P = 0.151); however, the differences were not significant. The duration of the hospital stay was longer in patients with T2DM than in those without T2DM (13.2 vs. 8.9 days, P < 0.05) and in patients with elevated versus normal HbA1c levels (14.5 vs. 11.4 days, P < 0.05). Diabetic GIC patients with elevated HbA1c levels had significantly more total postoperative complications than those with normal HbA1c levels (25.4% vs. 9.8%, P < 0.05). In multivariate regression analyses, short-term adverse outcomes were strongly associated with elevated HbA1c levels (odds ratio (OR): 5.276; 95% confidence level (CI): 1.73 - 16.095; P < 0.05) and no strict antidiabetic treatment (OR: 7.65; 95% CI: 2.49 - 23.54; P < 0.001). Conclusion An elevated level of HbA1c significantly correlated with and was an

  7. Impact of HbA1c Measurement on Hospital Readmission Rates: Analysis of 70,000 Clinical Database Patient Records

    PubMed Central

    Strack, Beata; DeShazo, Jonathan P.; Gennings, Chris; Olmo, Juan L.; Ventura, Sebastian; Cios, Krzysztof J.; Clore, John N.

    2014-01-01

    Management of hyperglycemia in hospitalized patients has a significant bearing on outcome, in terms of both morbidity and mortality. However, there are few national assessments of diabetes care during hospitalization which could serve as a baseline for change. This analysis of a large clinical database (74 million unique encounters corresponding to 17 million unique patients) was undertaken to provide such an assessment and to find future directions which might lead to improvements in patient safety. Almost 70,000 inpatient diabetes encounters were identified with sufficient detail for analysis. Multivariable logistic regression was used to fit the relationship between the measurement of HbA1c and early readmission while controlling for covariates such as demographics, severity and type of the disease, and type of admission. Results show that the measurement of HbA1c was performed infrequently (18.4%) in the inpatient setting. The statistical model suggests that the relationship between the probability of readmission and the HbA1c measurement depends on the primary diagnosis. The data suggest further that the greater attention to diabetes reflected in HbA1c determination may improve patient outcomes and lower cost of inpatient care. PMID:24804245

  8. Hot HB Stars in Globular Clusters - Physical Parameters and Consequences for Theory. VI. The Second Parameter Pair M3 and M13

    NASA Technical Reports Server (NTRS)

    Moehler, S.; Landsman, W. B.; Sweigart, A. V.; Grundahl, F.

    2002-01-01

    We present the results of spectroscopic analyses of hot horizontal branch (HB) stars in M13 and M3, which form a famous second parameter pair. From the spectra we derived - for the first time in M13 - atmospheric parameters (effective temperature and surface gravity) as well as abundances of helium, magnesium, and iron. Consistent with analyses of hot HB stars in other globular clusters we find evidence for helium depletion and iron enrichment in stars hotter than about 12,000 K in both M3 and M13. Accounting for the iron enrichment substantially improves the agreement with canonical evolutionary models, although the derived gravities and masses are still somewhat too low. This remaining discrepancy may be an indication that scaled-solar metal-rich model atmospheres do not adequately represent the highly non-solar abundance ratios found in blue HB stars with radiative levitation. We discuss the effects of an enhancement in the envelope helium abundance on the atmospheric parameters of the blue HB stars, as might be caused by deep mixing on the red giant branch or primordial pollution from an earlier generation of intermediate mass asymptotic giant branch stars.

  9. Hb East Timor [β80(EF4)Asn→His, AAC>CAC (HBB c.241A>C)], a variant hemoglobin associated with normal hematology.

    PubMed

    Finlayson, Jill; Ghassemifar, Reza; Holmes, Paula; Grey, Dianne; Figliomeni, Lisa; Newbound, Christopher; Pell, Nicole; Kersten, Michael; Jennens, Michelle; Macaulay, Claire; Greenwood, Laura; Beilby, John

    2010-01-01

    Routine hemoglobin (Hb) analyses identified a new β-globin variant in a family from East Timor. The red cell indices were within normal limits for all affected family members. The variant is due to a missense mutation at amino acid codon 80 (AAC>CAC) which results in the substitution of histidine for asparagine.

  10. Pediatric diabetes consortium type 1 diabetes new onset (NeOn) study: Factors associated with HbA1c levels one year after diagnosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To identify determinants of hemoglobin A1c (HbA1c) levels 1 yr after the diagnosis of type 1 diabetes (T1D) in participants in the Pediatric Diabetes Consortium (PDC) T1D New Onset (NeOn) Study. Diabetes-specific as well as socioeconomic factors during the first year following diagnosis were analyze...

  11. Microchromatography of hemoglobins. VIII. A general qualitative and quantitative method in plastic drinking straws and the quantitative analysis of Hb-F.

    PubMed

    Schroeder, W A; Pace, L A

    1978-03-01

    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.

  12. Microbial synthesis of a novel terpolyester P(LA-co-3HB-co-3HP) from low-cost substrates.

    PubMed

    Ren, Yilin; Meng, Dechuan; Wu, Linping; Chen, Jinchun; Wu, Qiong; Chen, Guo-Qiang

    2017-03-01

    Polylactide (PLA) is a bio-based plastic commonly synthesized by chemical catalytic reaction using lactic acid (LA) as a substrate. Here, novel LA-containing terpolyesters, namely, P[LA-co-3-hydroxybutyrate (3HB)-co-3-hydroxypropionate (3HP)], short as PLBP, were successfully synthesized for the first time by a recombinant Escherichia coli harbouring polyhydroxyalkanoate (PHA) synthase from Pseudomonas stutzeri (PhaC1Ps ) with 4-point mutations at E130D, S325T, S477G and Q481K, and 3-hydroxypropionyl-CoA (3HP-CoA) synthesis pathway from glycerol, 3-hydroxybutyryl-CoA (3HB-CoA) as well as lactyl-CoA (LA-CoA) pathways from glucose. Combining these pathways with the PHA synthase mutant phaC1Ps (E130D S325T S477G Q481K), the random terpolyester P(LA-co-3HB-co-3HP), or PLBP, was structurally confirmed by nuclear magnetic resonance to consist of 2 mol% LA, 90 mol% 3HB, and 8 mol% 3HP respectively. Remarkably, the PLBP terpolyester was produced from low-cost sustainable glycerol and glucose. Monomer ratios of PLBP could be regulated by ratios of glycerol to glucose. Other terpolyester thermal and mechanical properties can be manipulated by adjusting the monomer ratios. More PLBP applications are to be expected.

  13. Universal HbA1c Measurement in Early Pregnancy to Detect Type 2 Diabetes Reduces Ethnic Disparities in Antenatal Diabetes Screening: A Population-Based Observational Study

    PubMed Central

    2016-01-01

    In response to the type 2 diabetes epidemic, measuring HbA1c with the first-antenatal blood screen was recently recommended in NZ. This would enable prompt treatment of women with unrecognised type 2 diabetes, who may otherwise go undetected until the gestational diabetes (GDM) screen. We compare inter-ethnic antenatal screening practices to examine whether the HbA1c test would be accessed by ethnicities most at risk of diabetes, and we determined the prevalence of unrecognised type 2 diabetes and prediabetes in our pregnant population. This is an observational study of pregnancies in Christchurch NZ during 2008–2010. Utilising electronic databases, we matched maternal characteristics to first-antenatal bloods, HbA1c, and GDM screens (glucose challenge tests and oral glucose tolerance tests). Overall uptake of the first-antenatal bloods versus GDM screening was 83.1% and 53.8% respectively in 11,580 pregnancies. GDM screening was lowest in Māori 39.3%, incidence proportion ratio (IPR) 0.77 (0.71, 0.84) compared with Europeans. By including HbA1c with the first-antenatal bloods, the number screened for diabetes increases by 28.5% in Europeans, 40.0% in Māori, 28.1% in Pacific People, and 26.7% in ‘Others’ (majority of Asian descent). The combined prevalence of unrecognised type 2 diabetes and prediabetes by NZ criteria, HbA1c ≥5.9% (41mmol/mol), was 2.1% in Europeans, Māori 4.7% IPR 2.59 (1.71, 3.93), Pacific People 9.5% IPR 4.76 (3.10, 7.30), and ‘Others’ 6.2% IPR 2.99 (2.19, 4.07). Applying these prevalence data to 2013 NZ national births data, routine antenatal HbA1c testing could have identified type 2 diabetes in 0.44% and prediabetes in 3.96% of women. Routine HbA1c measurement in early pregnancy is an ideal screening opportunity, particularly benefitting vulnerable groups, reducing ethnic disparities in antenatal diabetes screening. This approach is likely to have world-wide relevance and applicability. Further research is underway to establish

  14. Genome-wide identification of Drosophila Hb9 targets reveals a pivotal role in directing the transcriptome within eight neuronal lineages, including activation of Nitric Oxide Synthase and Fd59a/Fox-D

    PubMed Central

    Lacin, Haluk; Rusch, Jannette; Yeh, Raymond T.; Fujioka, Miki; Wilson, Beth A.; Zhu, Yi; Robie, Alice A.; Mistry, Hemlata; Wang, Ting; Jaynes, James B.; Skeath, James B.

    2014-01-01

    Hb9 is a homeodomain-containing transcription factor that acts in combination with Nkx6, Lim3, and Tail-up (Islet) to guide the stereotyped differentiation, connectivity, and function of a subset of neurons in Drosophila. The role of Hb9 in directing neuronal differentiation is well documented, but the lineage of Hb9+ neurons is only partly characterized, its regulation is poorly understood, and most of the downstream genes through which it acts remain at large. Here, we complete the lineage tracing of all embryonic Hb9+ neurons (to eight neuronal lineages) and provide evidence that hb9, lim3, and tail-up are coordinately regulated by a common set of upstream factors. Through the parallel use of micro-array gene expression profiling and the Dam-ID method, we searched for Hb9-regulated genes, uncovering transcription factors as the most over-represented class of genes regulated by Hb9 (and Nkx6) in the CNS. By a nearly ten-to-one ratio, Hb9 represses rather than activates transcription factors, highlighting transcriptional repression of other transcription factors as a core mechanism by which Hb9 governs neuronal determination. From the small set of genes activated by Hb9, we characterized the expression and function of two – fd59a/foxd, which encodes a transcription factor, and Nitric oxide synthase. Under standard lab conditions, both genes are dispensable for Drosophila development, but Nos appears to inhibit hyper-active behavior and fd59a appears to act in octopaminergic neurons to control egg-laying behavior. Together our data clarify the mechanisms through which Hb9 governs neuronal specification and differentiation and provide an initial characterization of the expression and function of Nos and fd59a in the Drosophila CNS. PMID:24512689

  15. Existence of HbF Enhancer Haplotypes at HBS1L-MYB Intergenic Region in Transfusion-Dependent Saudi β-Thalassemia Patients.

    PubMed

    Cyrus, Cyril; Vatte, Chittibabu; Borgio, J Francis; Al-Rubaish, Abdullah; Chathoth, Shahanas; Nasserullah, Zaki A; Jarrash, Sana Al; Sulaiman, Ahmed; Qutub, Hatem; Alsaleem, Hassan; Alzahrani, Alhusain J; Steinberg, Martin H; Ali, Amein K Al

    2017-01-01

    Background and Objectives. β-Thalassemia and sickle cell disease are genetic disorders characterized by reduced and abnormal β-globin chain production, respectively. The elevation of fetal hemoglobin (HbF) can ameliorate the severity of these disorders. In sickle cell disease patients, the HbF level elevation is associated with three quantitative trait loci (QTLs), BCL11A, HBG2 promoter, and HBS1L-MYB intergenic region. This study elucidates the existence of the variants in these three QTLs to determine their association with HbF levels of transfusion-dependent Saudi β-thalassemia patients. Materials and Methods. A total of 174 transfusion-dependent β-thalassemia patients and 164 healthy controls from Eastern Province of Saudi Arabia were genotyped for fourteen single nucleotide polymorphisms (SNPs) from the three QTL regions using TaqMan assay on real-time PCR. Results. Genotype analysis revealed that six alleles of HBS1L-MYB QTL (rs9376090C p = 0.0009, rs9399137C p = 0.008, rs4895441G p = 0.004, rs9389269C p = 0.008, rs9402686A p = 0.008, and rs9494142C p = 0.002) were predominantly associated with β-thalassemia. In addition, haplotype analysis revealed that haplotypes of HBS1L-MYB (GCCGCAC p = 0.022) and HBG2 (GTT p = 0.009) were also predominantly associated with β-thalassemia. Furthermore, the HBS1L-MYB region also exhibited association with the high HbF cohort. Conclusion. The stimulation of HbF gene expression may provide alternative therapies for the amelioration of the disease severity of β-thalassemia.

  16. ERK1/2 Mediate Wounding- and G-protein-Coupled Receptor Ligands–Induced EGFR Activation via Regulating ADAM17 and HB-EGF Shedding

    PubMed Central

    Yin, Jia; Yu, Fu-Shin X.

    2013-01-01

    Purpose Previous studies have shown that wounding of human corneal epithelial cells (HCECs) results in the release of G-protein-coupled receptor ligands such as ATP and lysophosphatidic acid (LPA), which in turn transactivate epidermal growth factor (EGF) receptor (EGFR) through ectodomain shedding of heparin-binding EGF-like growth factor (HB-EGF). In the present study, the role of extracellular signal-regulated kinases 1/2 (ERK1/2) in regulating EGFR transactivation was investigated. Methods SV40-immortalized HCECs were wounded or stimulated with ATP and LPA. EGFR and ADAM17 activation was analyzed by immunoprecipitation followed by Western blot analysis with phospho-tyrosine or phospho-serine antibodies, respectively. Phosphorylation of ERK and AKT was analyzed by Western blot analysis. HB-EGF shedding was assessed by measuring the release of alkaline phosphatase (AP) in a stably transfected human corneal epithelial (THCE) cell line expressing HB-EGF-AP. ADAM17 and ERK interaction was determined by coimmunoprecipitation. Results Early, but not late, ERK1/2 phosphorylation in response to wounding, LPA, and ATP was EGFR independent, but sensitive to the inhibitors of calcium influx, protein kinase C and Src kinase. Wounding-, LPA-, and ATP-induced HB-EGF shedding and EGFR activation were attenuated by the MAPK/ERK kinase (MEK) inhibitors PD98059 and U0126, as well as by ADAM10 and -17 inhibitors. ADAM17 was found to be physically associated with active ERK and phosphorylated at serine residues in an ERK-dependent manner in wounded cells. Conclusions Taken together, our data suggest that in addition to functioning as an EGFR downstream effector, ERK1/2 also mediates ADAM-dependent HB-EGF shedding and subsequent EGFR transactivation in response to a variety of stimuli, including wounding and GPCR ligands. PMID:18658095

  17. Existence of HbF Enhancer Haplotypes at HBS1L-MYB Intergenic Region in Transfusion-Dependent Saudi β-Thalassemia Patients

    PubMed Central

    Vatte, Chittibabu; Borgio, J. Francis; Al-Rubaish, Abdullah; Nasserullah, Zaki A.; Jarrash, Sana Al; Sulaiman, Ahmed; Qutub, Hatem; Alsaleem, Hassan; Alzahrani, Alhusain J.; Steinberg, Martin H.

    2017-01-01

    Background and Objectives. β-Thalassemia and sickle cell disease are genetic disorders characterized by reduced and abnormal β-globin chain production, respectively. The elevation of fetal hemoglobin (HbF) can ameliorate the severity of these disorders. In sickle cell disease patients, the HbF level elevation is associated with three quantitative trait loci (QTLs), BCL11A, HBG2 promoter, and HBS1L-MYB intergenic region. This study elucidates the existence of the variants in these three QTLs to determine their association with HbF levels of transfusion-dependent Saudi β-thalassemia patients. Materials and Methods. A total of 174 transfusion-dependent β-thalassemia patients and 164 healthy controls from Eastern Province of Saudi Arabia were genotyped for fourteen single nucleotide polymorphisms (SNPs) from the three QTL regions using TaqMan assay on real-time PCR. Results. Genotype analysis revealed that six alleles of HBS1L-MYB QTL (rs9376090C p = 0.0009, rs9399137C p = 0.008, rs4895441G p = 0.004, rs9389269C p = 0.008, rs9402686A p = 0.008, and rs9494142C p = 0.002) were predominantly associated with β-thalassemia. In addition, haplotype analysis revealed that haplotypes of HBS1L-MYB (GCCGCAC p = 0.022) and HBG2 (GTT p = 0.009) were also predominantly associated with β-thalassemia. Furthermore, the HBS1L-MYB region also exhibited association with the high HbF cohort. Conclusion. The stimulation of HbF gene expression may provide alternative therapies for the amelioration of the disease severity of β-thalassemia. PMID:28280727

  18. A Comparison of hs-CRP Levels in New Diabetes Groups Diagnosed Based on FPG, 2-hPG, or HbA1c Criteria.

    PubMed

    Tutuncu, Yildiz; Satman, Ilhan; Celik, Selda; Dinccag, Nevin; Karsidag, Kubilay; Telci, Aysegul; Genc, Sema; Issever, Halim; Tuomilehto, Jaakko; Omer, Beyhan

    2016-01-01

    Fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) have been used to diagnose new-onset diabetes mellitus (DM) in order to simplify the diagnostic tests compared with the 2-hour oral glucose tolerance test (OGTT; 2-hPG). We aimed to identify optimal cut-off points of high sensitive C-reactive protein (hs-CRP) in new-onset DM people based on FPG, 2-hPG, or HbA1c methods. Data derived from recent population-based survey in Turkey (TURDEP-II). The study included 26,499 adult people (63% women, response rate 85%). The mean serum concentration of hs-CRP in women was higher than in men (p < 0.001). The people with new-onset DM based on HbA1c had higher mean hs-CRP level than FPG based and 2-hPG based DM cases. In HbA1c, 2-hPG, and FPG based new-onset DM people, cut-off levels of hs-CRP in women were 2.9, 2.1, and 2.5 mg/L [27.5, 19.7, and 23.5 nmol/L] and corresponding values in men were 2.0, 1.8, and 1.8 mg/L (19.0, 16.9, and 16.9 nmol/L), respectively (sensitivity 60-65% and specificity 54-64%). Our results revealed that hs-CRP may not further strengthen the diagnosis of new-onset DM. Nevertheless, the highest hs-CRP level observed in new-onset DM people diagnosed with HbA1c criterion supports the general assumption that this method might recognize people in more advanced diabetic stage compared with other diagnostic methods.

  19. Ectodomain cleavage of the EGF ligands HB-EGF, neuregulin1-beta, and TGF-alpha is specifically triggered by different stimuli and involves different PKC isoenzymes.

    PubMed

    Herrlich, Andreas; Klinman, Eva; Fu, Jonathan; Sadegh, Cameron; Lodish, Harvey

    2008-12-01

    Metalloproteinase cleavage of transmembrane proteins (ectodomain cleavage), including the epidermal growth factor (EGF) ligands heparin-binding EGF-like growth factor (HB-EGF), neuregulin (NRG), and transforming growth factor-alpha (TGF-alpha), is important in many cellular signaling pathways and is disregulated in many diseases. It is largely unknown how physiological stimuli of ectodomain cleavage--hypertonic stress, phorbol ester, or activation of G-protein-coupled receptors [e.g., by lysophosphatidic acid (LPA)]--are molecularly connected to metalloproteinase activation. To study this question, we developed a fluorescence-activated cell sorting (FACS)- based assay that measures cleavage of EGF ligands in single living cells. EGF ligands expressed in mouse lung epithelial cells are differentially and specifically cleaved depending on the stimulus. Inhibition of protein kinase C (PKC) isoenzymes or metalloproteinase inhibition by batimastat (BB94) showed that different regulatory signals are used by different stimuli and EGF substrates, suggesting differential effects that act on the substrate, the metalloproteinase, or both. For example, hypertonic stress led to strong cleavage of HB-EGF and NRG but only moderate cleavage of TGF-alpha. HB-EGF, NRG, and TGF-alpha cleavage was not dependent on PKC, and only HB-EGF and NRG cleavage were inhibited by BB94. In contrast, phorbol 12-myristate-13-acetate (TPA) -induced cleavage of HB-EGF, NRG, and TGF-alpha was dependent on PKC and sensitive to BB94 inhibition. LPA led to significant cleavage of only NRG and TGF-alpha and was inhibited by BB94; only LPA-induced NRG cleavage required PKC. Surprisingly, specific inhibition of atypical PKCs zeta and iota [not activated by diacylglycerol (DAG) and calcium] significantly enhanced TPA-induced NRG cleavage. Employed in a high-throughput cloning strategy, our cleavage assay should allow the identification of candidate proteins involved in signal transduction of different

  20. [Effects of applying behavior modification to improve HbA1C levels in a diabetic patient].

    PubMed

    Chen, Wen-Chun; Huang, You-Rong; Lin, Chiu-Chu

    2010-04-01

    Diabetes is a chronic disease. To prevent and delay complications, diabetic patients must adjust their lifestyle as part of a comprehensive approach to disease control. Diabetic patients must be able to self-manage their disease and establish healthy habits in their daily routine. In this study, prior to intervention, the subject was unable to control her diet, do exercise, check sugars properly or integrate disease management effectively into her daily routine. By applying self-regulation theory through the keeping of a diary for sugar and daily activity self-monitoring, she became able to self-assess the causes of poor disease control. Such further facilitated her setting goals and developing strategies to link her habits with disease management. When failing to achieve goals even after execution, she could consider the factors contributing to the failure and modify her behaviors, goals and/or strategies accordingly. We helped this patient learn behavior modification methods in order to achieve her goal of better HbA(1)C control. This case example may help clinical nursing educators move beyond the confines of the traditional one-way educational model to guide diabetic patients to achieve good sugar control. We hope our findings help many chronic disease sufferers achieve self-management objectives in order to assume greater self-care responsibilities.

  1. Single Stage Single Switch Power Supply (S4PS)Design for Low Power HB-LED Lighting

    NASA Astrophysics Data System (ADS)

    Shrivastava, Ashish; Singh, Bhim

    2013-05-01

    This paper presents an improved power quality converter (IPQC)-based power supply design for high brightness light emitting diode (HB-LED) low power lighting. The IPQC circuit uses a Cuk buck-boost converter to operate it in a discontinuous conduction mode (DCM) using the voltage follower technique for the mitigation of harmonic contents present in the AC mains current. Subsequently, reduction in harmonic contents results in improving the power quality indices at the AC mains. Single-stage single switch converter topology is used, which has less component count, size and cost as compared to the two-stage converter topology. DCM operation has an advantage that only output voltage control loop is required as compared to three control loops required in the continuous conduction mode operation. An 18-W LED driver is designed, modeled and simulated using MATLAB/Simulink software for 220 V, 50 Hz AC mains. The performance of the proposed LED driver is observed in terms of total harmonic distortion of the input current (THDi), input power factor (PF) and crest factor (CF) taking into account the strict international standard of IEC 61000-3-2 for class C equipments.

  2. Notch increases the shedding of HB-EGF by ADAM12 to potentiate invadopodia formation in hypoxia.

    PubMed

    Díaz, Begoña; Yuen, Angela; Iizuka, Shinji; Higashiyama, Shigeki; Courtneidge, Sara A

    2013-04-15

    Notch regulates cell-cell contact-dependent signaling and is activated by hypoxia, a microenvironmental condition that promotes cellular invasion during both normal physiology and disease. The mechanisms by which hypoxia and Notch regulate cellular invasion are not fully elucidated. In this paper, we show that, in cancer cells, hypoxia increased the levels and activity of the ADAM12 metalloprotease in a Notch signaling-dependent manner, leading to increased ectodomain shedding of the epidermal growth factor (EGF) receptor (EGFR) ligand heparin-binding EGF-like growth factor. Released HB-EGF induced the formation of invadopodia, cellular structures that aid cancer cell invasion. Thus, we describe a signaling pathway that couples cell contact-dependent signaling with the paracrine activation of the EGFR, indicating cross talk between the Notch and EGFR pathways in promoting cancer cell invasion. This signaling pathway might regulate the coordinated acquisition of invasiveness by neighboring cells and mediate the communication between normoxic and hypoxic areas of tumors to facilitate cancer cell invasion.

  3. Hb Lansing (HBA2: c.264C > G) and a new β promoter transversion [-52 (G > T)]: an attempt to define the phenotype of two mutations found in the Omani population.

    PubMed

    Hassan, Suha M; Harteveld, Cornelis L; Bakker, Engbert; Giordano, Piero C

    2015-01-01

    We report two examples showing how problematic it can be to define the phenotype of new or rare globin genes mutations. We describe two mutations observed for the first time in the Omani population: the first was found in the consanguineous parents of a deceased newborn with hepatomegaly, cardiomegaly and severe hemolytic anemia, putatively homozygous for the rare Hb Lansing (HBA2: c.264C > G) variant. The second is a novel β-globin gene promoter mutation [-52 (G > T)] observed in four independent patients. Two with borderline/elevated Hb A2, α-thalassemia (α-thal) and hypochromic red cell indices, and two heterozygotes for Hb S (HBB: c.20A > T), α-thal and with Hb A/Hb S ratios possibly indicating a very mild β(+)-thalassemia (β(+)-thal) mutation.

  4. Comparison of radial immunodiffusion and alkaline cellulose acetate electrophoresis for quantitating elevated levels of fetal hemoglobin (HbF): application to evaluating patients with sickle cell disease treated with hydroxyurea.

    PubMed

    Schultz, J C

    1999-01-01

    Radial immunodiffusion (RID), alkaline cellulose acetate electrophoresis, and high-performance liquid chromatography (HPLC) were compared for quantitating the elevated (> 10%) level of fetal hemoglobin (HbF) found in the red blood cells of sickle cell disease patients undergoing treatment with hydroxyurea. HPLC- and electrophoresis-determined values were comparable. The RID-determined values were higher, in many cases twofold higher. False high HbF values would be misleading in assessing the effectiveness of hydroxyurea therapy in sickle cell disease patients. We subsequently initiated an examination of the variation in HbF values due to the use of different HbF radial immunodiffusion QUIPlates and different positions within a single plate in an attempt to determine the cause of these discrepancies. Within-run precision studies indicated that significantly different size precipitin rings were obtained depending upon which area of the plate the hemolysate containing antigen (HbF) was applied. A common feature associated with poor precision plates was a marked difference in degree of coloration of gel throughout the plate. Spuriously high HF concentrations were obtained with antigen (HbF) placed in wells located in the lighter colored gel area while antigen placed in wells in the darker colored area of the agarose gel bed were more in agreement with the electrophoretically determined HbF concentrations. The variation in HbF values was significantly greater in the diluted (HbF QUIPlate Diluent) samples than in the neat samples even on plates of uniform gel coloration. As a result of this study, we will continue to monitor high HbF levels by densitometry following alkaline cellulose acetate electrophoresis.

  5. Evaluation of the effects of nano-TiO2 on bioactivity and mechanical properties of nano bioglass-P3HB composite scaffold for bone tissue engineering.

    PubMed

    Bakhtiyari, Sanaz Soleymani Eil; Karbasi, Saeed; Monshi, Ahmad; Montazeri, Mahbobeh

    2016-01-01

    To emulate bone structure, porous composite scaffold with suitable mechanical properties should be designed. In this research the effects of nano-titania (nTiO2) on the bioactivity and mechanical properties of nano-bioglass-poly-3-hydroxybutyrate (nBG/P3HB)-composite scaffold were evaluated. First, nBG powder was prepared by melting method of pure raw materials at a temperature of 1400 °C and then the porous ceramic scaffold of nBG/nTiO2 with 30 wt% of nBG containing different weight ratios of nTiO2 (3, 6, and 9 wt% of nTiO2 with grain size of 35-37 nm) was prepared by using polyurethane sponge replication method. Then the scaffolds were coated with P3HB in order to increase the scaffold's mechanical properties. Mechanical strength and modulus of scaffolds were improved by adding nTiO2 to nBG scaffold and adding P3HB to nBG/nTiO2 composite scaffold. The results of the compressive strength and porosity tests showed that the best scaffold is 30 wt% of nBG with 6 wt% of nTiO2 composite scaffold immersed for 30 s in P3HB with 79.5-80 % of porosity in 200-600 μm, with a compressive strength of 0.15 MPa and a compressive modulus of 30 MPa, which is a good candidate for bone tissue engineering. To evaluate the bioactivity of the scaffold, the simulated body fluid (SBF) solution was used. The best scaffold with 30 wt% of nBG, 6 wt% of P3HB and 6 wt% of nTiO2 was immersed in SBF for 4 weeks at an incubation temperature of 37 °C. The bioactivity of the scaffolds was characterized by AAS, SEM, EDXA and XRD. The results of bioactivity showed that bone-like apatite layer formed well at scaffold surface and adding nTiO2 to nBG/P3HB composite scaffold helped increase the bioactivity rate.

  6. Driving Down HB-LED Costs. Implementation of Process Simulation Tools and Temperature Control Methods of High Yield MOCVD Growth

    SciTech Connect

    Quinn, William

    2012-04-30

    The overall objective of this multi-faceted program is to develop epitaxial growth systems that meet a goal of 75% (4X) cost reduction in the epitaxy phase of HB-LED manufacture. A 75% reduction in yielded epitaxy cost is necessary in order to achieve the cost goals for widespread penetration of HB-LED's into back-lighting units (BLU) for LCD panels and ultimately for solid-state lighting (SSL). To do this, the program will address significant improvements in overall equipment Cost of Ownership, or CoO. CoO is a model that includes all costs associated with the epitaxy portion of production. These aspects include cost of yield, capital cost, operational costs, and maintenance costs. We divide the program into three phases where later phases will incorporate the gains of prior phases. Phase one activities are enabling technologies. In collaboration with Sandia National Laboratories we develop a Fluent-compatible chemistry predictive model and a set of mid-infrared and near-ultraviolet pyrometer monitoring tools. Where previously the modeling of the reactor dynamics were studied within FLUENT alone, here, FLUENT and Chemkin are integrated into a comprehensive model of fluid dynamics and the most advanced transport equations developed for Chemkin. Specifically, the Chemkin model offered the key reaction terms for gas-phase nucleation, a key consideration in the optimization of the MOCVD process. This new predictive model is used to design new MOCVD reactors with optimized growth conditions and the newly developed pyrometers are used monitor and control the MOCVD process temperature to within 0.5°C run-to-run and within each wafer. This portion of the grant is in collaboration with partners at Sandia National Laboratories. Phase two activities are continuous improvement projects which extend the current reactor platform along the lines of improved operational efficiency, improved systems control for throughput, and carrier modifications for increased yield

  7. Unraveling the molecular basis for ligand binding in truncated hemoglobins: the trHbO Bacillus subtilis case.

    PubMed

    Boechi, Leonardo; Mañez, Pau Arroyo; Luque, F Javier; Marti, Marcelo A; Estrin, Dario A

    2010-03-01

    Truncated hemoglobins (trHbs) are heme proteins present in bacteria, unicellular eukaryotes, and higher plants. Their tertiary structure consists in a 2-over-2 helical sandwich, which display typically an inner tunnel/cavity system for ligand migration and/or storage. The microorganism Bacillus subtilis contains a peculiar trHb, which does not show an evident tunnel/cavity system connecting the protein active site with the solvent, and exhibits anyway a very high oxygen association rate. Moreover, resonant Raman results of CO bound protein, showed that a complex hydrogen bond network exists in the distal cavity, making it difficult to assign unambiguously the residues involved in the stabilization of the bound ligand. To understand these experimental results with atomistic detail, we performed classical molecular dynamics simulations of the oxy, carboxy, and deoxy proteins. The free energy profiles for ligand migration suggest that there is a key residue, GlnE11, that presents an alternate conformation, in which a wide ligand migration tunnel is formed, consistently with the kinetic data. This tunnel is topologically related to the one found in group I trHbs. On the other hand, the results for the CO and O(2) bound protein show that GlnE11 is directly involved in the stabilization of the cordinated ligand, playing a similar role as TyrB10 and TrpG8 in other trHbs. Our results not only reconcile the structural data with the kinetic information, but also provide additional insight into the general behaviour of trHbs. Proteins 2010. (c) 2009 Wiley-Liss, Inc.

  8. Transcriptional Repression Mediated by a TetR Family Protein, PfmR, from Thermus thermophilus HB8

    PubMed Central

    Agari, Yoshihiro; Sakamoto, Keiko; Kuramitsu, Seiki

    2012-01-01

    PfmR is one of four TetR family transcriptional regulators found in the extremely thermophilic bacterium, Thermus thermophilus HB8. We identified three promoters with strong negative regulation by PfmR, both in vivo and in vitro. PfmR binds pseudopalindromic sequences, with the consensus sequence of 5′-TACCGACCGNTNGGTN-3′ surrounding the promoters. According to the amino acid sequence and three-dimensional structure analyses of the PfmR-regulated gene products, they are predicted to be involved in phenylacetic acid and fatty acid metabolism. In vitro analyses revealed that PfmR weakly cross-regulated with the TetR family repressor T. thermophilus PaaR, which controls the expression of the paa gene cluster putatively involved in phenylacetic acid degradation but not with another functionally identified TetR family repressor, T. thermophilus FadR, which is involved in fatty acid degradation. The X-ray crystal structure of the N-terminal DNA-binding domain of PfmR and the nucleotide sequence of the predicted PfmR-binding site are quite similar to those of the TetR family repressor QacR from Staphylococcus aureus. Similar to QacR, two PfmR dimers bound per target DNA. The bases recognized by QacR within the QacR-binding site are conserved in the predicted PfmR-binding site, and they were important for PfmR to recognize the binding site and properly assemble on it. The center of the PfmR molecule contains a tunnel-like pocket, which may be the ligand-binding site of this regulator. PMID:22753056

  9. Metabolic network reconstruction, growth characterization and 13C-metabolic flux analysis of the extremophile Thermus thermophilus HB8.

    PubMed

    Swarup, Aditi; Lu, Jing; DeWoody, Kathleen C; Antoniewicz, Maciek R

    2014-07-01

    Thermus thermophilus is an extremely thermophilic bacterium with significant biotechnological potential. In this work, we have characterized aerobic growth characteristics of T. thermophilus HB8 at temperatures between 50 and 85°C, constructed a metabolic network model of its central carbon metabolism and validated the model using (13)C-metabolic flux analysis ((13)C-MFA). First, cells were grown in batch cultures in custom constructed mini-bioreactors at different temperatures to determine optimal growth conditions. The optimal temperature for T. thermophilus grown on defined medium with glucose was 81°C. The maximum growth rate was 0.25h(-1). Between 50 and 81°C the growth rate increased by 7-fold and the temperature dependence was described well by an Arrhenius model with an activation energy of 47kJ/mol. Next, we performed a (13)C-labeling experiment with [1,2-(13)C] glucose as the tracer and calculated intracellular metabolic fluxes using (13)C-MFA. The results provided support for the constructed network model and highlighted several interesting characteristics of T. thermophilus metabolism. We found that T. thermophilus largely uses glycolysis and TCA cycle to produce biosynthetic precursors, ATP and reducing equivalents needed for cells growth. Consistent with its proposed metabolic network model, we did not detect any oxidative pentose phosphate pathway flux or Entner-Doudoroff pathway activity. The biomass precursors erythrose-4-phosphate and ribose-5-phosphate were produced via the non-oxidative pentose phosphate pathway, and largely via transketolase, with little contribution from transaldolase. The high biomass yield on glucose that was measured experimentally was also confirmed independently by (13)C-MFA. The results presented here provide a solid foundation for future studies of T. thermophilus and its metabolic engineering applications.

  10. Combined FISH, anti-γ-Hb and DAPI for detection of fetal nucleated RBCs in maternal blood

    NASA Astrophysics Data System (ADS)

    Farhad, Mona; Price, Jeffrey H.

    2002-05-01

    Since the 1970s, extensive research has been devoted to the development of a standard procedure for the isolation of fetal nucleated red cells (fnRBCs) from maternal blood. Since these cells are sources of fetal DNA, cytogenetic analysis would lead to a minimally-invasive method for the prenatal diagnosis of chromosomal and genetic disorders early in gestation. FnRBCs constitute a significant portion of the fetal blood, have a short and finite life span, and are rare in peripheral adult blood. They have been reported to exist in the maternal circulation at frequencies as low as 1:105 - 1:109 maternal nucleated cells. Due to these ultra-rare frequencies, isolation with minimal loss has been a time and labor-intensive process. To overcome this problem, a fully automated scanning cytometer that incorporates high-performance autofocus and image segmentation has been built and shown higher rate, quantity, sensitivity (true positive rate) and specificity (true negative rate) in a model cell preparation. For detecting fnRBCs, two discriminating characteristics may suffice: (1) the presence of fetal hemoglobin, which is the major intracytoplasmic protein found in fetal red cells from 5 to 35 weeks gestation, and (2) the presence of a nucleus. In clinical trials, the fetal origin of the isolated cells will be confirmed by fluorescence in situ hybridization (FISH) on the X and Y chromosomes in male pregnancies. The aim of the present study was to develop a reliable and reproducible staining method for combined immunofluorescence and FISH analysis for these clinical trials. This staining technique was developed using fnRBCs extracted from fetal liver blood and a human erythroleukemia cell line (HEL) that expresses fetal hemoglobin. The resulting method for four-color X- and Y-FISH , anti-(gamma) -Hb fluorescence and DAPI staining was consistent and bright.

  11. Isolation and characterization of Bacteroides host strain HB-73 used to detect sewage specific phages in Hawaii.

    PubMed

    Vijayavel, Kannappan; Fujioka, Roger; Ebdon, James; Taylor, Huw

    2010-06-01

    Previous studies have shown that Escherichia coli and enterococci are unreliable indicators of fecal contamination in Hawaii because of their ability to multiply in environmental soils. In this study, the method of detecting Bacteroides phages as specific markers of sewage contamination in Hawaii's recreational waters was evaluated because these sewage specific phages cannot multiply under environmental conditions. Bacteroides hosts (GB-124, GA-17), were recovered from sewage samples in Europe and were reported to be effective in detecting phages from sewage samples obtained in certain geographical areas. However, GB-124 and GA-17 hosts were ineffective in detecting phages from sewage samples obtained in Hawaii. Bacteroides host HB-73 was isolated from a sewage sample in Hawaii, confirmed as a Bacteroides sp. and shown to recover phages from multiple sources of sewage produced in Hawaii at high concentrations (5.2-7.3 x 10(5) PFU/100 mL). These Bacteroides phages were considered as potential markers of sewage because they also survived for three days in fresh stream water and two days in marine water. Water samples from Hawaii's coastal swimming beaches and harbors, which were known to be contaminated with discharges from streams, were shown to contain moderate (20-187 CFU/100 mL) to elevated (173-816 CFU/100 mL) concentrations of enterococci. These same samples contained undetectable levels (<10 PFU/100 mL) of F+ coliphage and Bacteroides phages and provided evidence to suggest that these enterococci may not necessarily be associated with the presence of raw sewage. These results support previous conclusions that discharges from streams are the major sources of enterococci in coastal waters of Hawaii and the most likely source of these enterococci is from environmental soil rather than from sewage.

  12. Comparison of Massimo Pronto-7 and HemoCue Hb 201+ with laboratory haemoglobin estimation: a clinical study.

    PubMed

    Hiscock, R; Simmons, Sw; Carstensen, B; Gurrin, Lc

    2014-09-01

    We prospectively studied agreement in haemoglobin estimation between two point-of-care devices (Pronto-7(®) Pulse CO-Oximetry(™), Masimo Corporation, Irvine, California, USA and HemoCue(®) Hb 201 +, HemoCue, Angelholm, Sweden) and an automated laboratory analyser (Sysmex XE5000, Sysmex Corporation, Kobe, Japan). Venous blood sampling and finger co-oximeter readings were performed on 141 pregnant women undergoing routine mid-trimester haemoglobin assessment. Three replicate measures were performed and analysis used Bayesian-based variance component modelling to provide estimates of repeatability, between person within method bias and precision. Repeatability, assessed by coefficient of variation, was higher for Pronto-7(®) (2.3%) compared to HemoCue(®) (5.2%). Fixed bias (mean difference, device - laboratory) was +1.18 (standard deviation 1.19) g/dl and - 0.01 (standard deviation 1.34) g/dl for Pronto-7(®) and HemoCue(®) respectively, with no statistical evidence of proportional bias. Based upon a single device reading, the 95% prediction limits for Pronto-7(®) were -1.2 to 3.6 g.dl-1 and HemoCue(®) were -2.7 to 2.7 g/dl. For both devices precision was not meaningfully improved by averaging replicate readings. However, repeated readings may allow detection of aberrant results. Overall both devices are imprecise and 95% prediction limits wide. We present further prediction limits, derived from the posterior distribution and adjusted for any fixed bias for set levels of probability (certainty). These may be used to support clinical decisions when using these point-of-care devices.

  13. Heparin-binding EGF-like growth factor (HB-EGF) overexpression in transgenic mice downregulates insulin-like growth factor binding protein (IGFBP)-3 and -4 mRNA.

    PubMed

    Provenzano, Aaron P; Besner, Gail E; James, Paul F; Harding, Paul A

    2005-03-01

    An in vivo approach was taken to assess the biological significance of heparin-binding EGF-like growth factor (HB-EGF) using transgenic mice. Transgenic mice were generated using the pIRES-EGFP vector expressing a bicistronic mRNA containing both human HB-EGF (hHB-EGF) and enhanced green fluorescent protein (EGFP) coding sequences under the regulation of the cytomegalovirus immediate-early (CMV-IE) promoter. As a marker for transgene expression, EGFP fluorescence in 5 microm tissue sections was evaluated. To confirm HB-EGF expression in EGFP-containing tissues, HB-EGF mRNA was analyzed by RT-PCR and Northern blot analysis. Protein levels of HB-EGF and insulin-like growth factor binding protein-3 (IGFBP-3), a molecule that stabilizes IGFs, which in turn helps to promote growth, were analyzed by Western blot. Also, the weights of transgenic mice were compared with the weights of wild type non-transgenic littermates over a 10-week period. EGFP fluorescence, RT-PCR and Northern analysis of a variety of tissues from hHB-EGF transgenic mice indicate recombinant EGFP/hHB-EGF mRNA expression in kidney, liver, lung and stomach. Western blot analysis confirmed that HB-EGF protein levels were greater in these tissues from hHB-EGF transgenic mice compared to wild type non-transgenic littermates. IGFBP-3 protein was absent in serum of transgenic mice prior to the onset of puberty, but indistinguishable from wild type non-transgenic mice after puberty. Furthermore, IGFBP-3 and IGFBP-4 mRNA were downregulated in the kidney, but not liver or lung of the transgenic mice. In accordance with reduced IGFBP-3 and -4 levels, hHB-EGF transgenic mice exhibited a 20% decrease in weight prior to 6 weeks of age compared to wild type non-transgenic littermates. Our laboratory has generated a biologically functional transgenic mouse model exhibiting increased expression of hHB-EGF in kidney, liver, lung and stomach. Overexpression of hHB-EGF affected the growth rate of these transgenic mice

  14. Complete genome sequence of Thermovibrio ammonificans HB-1T, a thermophilic, chemolithoautotrophic bacterium isolated from a deep-sea hydrothermal vent

    SciTech Connect

    Giovannelli, Donato; Ricci, Jessica; Perez-Rodriguez, Ileana; Hugler, Michael; O'Brien, Charles; Keddis, Ramaydalis; Grosche, Ashley; Goodwin, Lynne A.; Bruce, David; Davenport, Karen W.; Detter, J. Chris; Han, James; Han, Cliff; Ivanova, N; Land, Miriam L; Mikhailova, Natalia; Nolan, Matt; Pitluck, Sam; Tapia, Roxanne; Woyke, Tanja; Vetriani, Costantino

    2012-01-01

    Thermovibrio ammonificans type strain HB-1T is a thermophilic (Topt: 75 C), strictly anaero- bic, chemolithoautotrophic bacterium that was isolated from an active, high temperature deep-sea hydrothermal vent on the East Pacific Rise. This organism grows on mineral salts medium in the presence of CO2/H2, using NO3- or S0 as electron acceptors, which are re- duced to ammonium or hydrogen sulfide, respectively. T. ammonificans is one of only three species within the genus Thermovibrio, a member of the family Desulfurobacteriaceae, and it forms a deep branch within the phylum Aquificae. Here we report the main features of the genome of T. ammonificans strain HB-1T (DSM 15698T).

  15. Ryd4 (Hb): a novel resistance gene introgressed from Hordeum bulbosum into barley and conferring complete and dominant resistance to the barley yellow dwarf virus.

    PubMed

    Scholz, Margret; Ruge-Wehling, Brigitte; Habekuss, Antje; Schrader, Otto; Pendinen, Galina; Fischer, Kristin; Wehling, Peter

    2009-09-01

    Barley yellow dwarf virus (BYDV) causes high yield losses in most of the major cereal crops worldwide. A source of very effective resistance was detected within the tetraploid wild species of Hordeum bulbosum. Interspecific crosses between a resistant H. bulbosum accession and H. vulgare cv. 'Igri' were performed to transfer this resistance into cultivated barley. Backcrosses to H. vulgare resulted in offspring which carried a single subterminal introgression of H. bulbosum chromatin on barley chromosome 3HL and proved to be fully resistant to BYDV-PAV, as inferred by ELISA values of zero or close to zero and lack of BYDV symptoms. Genetic analysis indicated a dominant inheritance of the BYDV-PAV resistance factor, which we propose to denote Ryd4 ( Hb ) . The identity and effect of Ryd4 ( Hb ) are discussed in relation to other known genes for BYDV resistance or tolerance, as well as the relevance of this gene for resistance breeding in barley.

  16. Integrative health coaching: a behavior skills approach that improves HbA1c and pharmacy claims-derived medication adherence

    PubMed Central

    Wolever, Ruth Q; Dreusicke, Mark H

    2016-01-01

    Objective Medication adherence requires underlying behavior skills and a supporting mindset that may not be addressed with education or reminders. Founded in the study of internal motivation and health psychology, integrative health coaching (IHC) helps patients gain insight into their behaviors and make long-term, sustainable lifestyle changes. The purpose of the study is to determine whether IHC improves oral medication adherence, glycated hemoglobin (HbA1c), and psychosocial measures, and to assess whether adherence changes are sustained after the intervention. Methods Using a prospective observational design, participants (n=56) received 14 coaching calls by telephone over 6 months. Medication possession ratio (MPR) was calculated for time intervals before, during, and after the intervention. HbA1c and patient-reported psychosocial outcomes were obtained to test interactions with MPR. Results Medication adherence (MPR) increased from 0.74±0.197 to 0.85±0.155 during coaching, and was sustained at 0.82±0.175 during a 6-month period after the study. Better adherence correlated with a greater decrease in HbA1c. HbA1c decreased from 8.0±1.92% to 7.7±1.70% over the 6-month intervention. All psychosocial measures showed significant improvement. In addition to discussing medication adherence strategies with their coach, patients discussed nutrition and exercise (86.9% of calls), stress management (39.8%), and social support and relationships (15.4%). Conclusions IHC targets internal motivation and supports behavior change by facilitating patients’ insight into their own behaviors, and it uses this insight to foster self-efficacy. This approach may yield sustainable results for medication adherence and warrants further exploration for health-related behavior change. PMID:27239318

  17. Abnormal expression and function of Dectin-1 receptor in type 2 diabetes mellitus patients with poor glycemic control (HbA1c>8%).

    PubMed

    Cortez-Espinosa, Nancy; García-Hernández, Mariana H; Reynaga-Hernández, Elizabeth; Cortés-García, J Diego; Corral-Fernández, Nancy E; Rodríguez-Rivera, J Guillermo; Bravo-Ramírez, Anamaría; González-Amaro, Roberto; Portales-Pérez, Diana P

    2012-11-01

    Dectin-1 is a key innate receptor involved in various cellular responses and may have a direct role in chronic inflammatory conditions such as type 2 diabetes mellitus. The aim of this work was to evaluate the expression and function of Dectin-1 in peripheral blood mononuclear cells from T2D patients. Dectin-1 expression was analyzed by flow cytometry and RT-PCR in monocytes and lymphocyte subpopulations from T2D patients (n=34) and healthy subjects (n=29). Functional assays were used to assess cytokine synthesis, ROS levels and oxidative stress ratio. We found increased expression (MFI) of Dectin-1 in monocytes from T2D patients. Significantly higher Dectin-1 expression was also detected in CD4(+) T, CD8(+) T, B cells and NK cells from T2D patients compared to controls. In contrast, monocytes from T2D patients with poor glycemic control (HbA1c>8%) showed a diminished percentage of Dectin-1(+)/TLR2(+) cells. Negative correlations between the percent of Dectin-1(+)/TLR2(+) cells and fasting plasma glucose levels (FPG) and HbA1c levels were found. A significant reduction in basal levels of IL-10 was observed in patients with poor glycemic control (HbA1c>8%) compared to patients with appropriate glycemic control (HbA1c≤6.5%) and healthy controls, an effect that was not observed in monocytes stimulated with zymosan. Higher ROS levels in zymosan-stimulated cells from patients with poor glycemic control positively correlated with FPG levels, and the oxidative stress ratio was higher in T2D cells compared with controls. Our data indicate that Dectin-1 may be involved in the abnormal immune responses that are observed in patients with T2D.

  18. An engineered heparin-binding form of VEGF-E (hbVEGF-E). Biological effects in vitro and mobilizatiion of precursor cells.

    PubMed

    Heil, Matthias; Mitnacht-Krauss, Rita; Issbrücker, Katja; van den Heuvel, Joop; Dehio, Christoph; Schaper, Wolfgang; Clauss, Matthias; Weich, Herbert A

    2003-01-01

    Vascular endothelial growth factor (VEGF-A) is the founding member of a family of angiogenic proteins with various binding abilities to three cognate VEGF receptors. Previously, a gene encoding from the genome of parapox orf virus (OV) with about 25% amino acid identity to mammalian VEGF-A was named VEGF-E and shown to bind and specifically activate the vascular endothelial growth factor receptor VEGFR-2 (KDR/flk-1). Here, we have generated a novel heparin-binding form of VEGF-E by introducing the heparin-domain of the human VEGF-A(165) splice variant into the viral VEGF-E protein. Recombinant heparin-binding VEGF-E (hbVEGF-E) is shown to stimulate proliferation and sprout formation of macro- and microvascular endothelial cells to a similar extent as the parental OV-VEGF-E but fails to activate peripheral mononuclear cells. However, hbVEGF-E is more potent in binding competition assays with primary human endothelial cells when compared to the OV-VEGF-E. This can be explained by our finding that binding of hbVEGF-E but not of parental OV-VEGF-E to the VEGFR-2 is strongly increased by the addition of neuropilin-1 (NP-1), a cognate co-receptor for VEGF-A. The engineered hbVEGF-E was compared with the VEGFR-1 selective and also heparin-binding form of placenta growth factor (PlGF-2) in vivo. Both heparin-binding homologues induced mobilization of endothelial progenitor cells from the bone marrow and gave rise to similar colony numbers of myeloic cells in a colony-forming assay. These findings suggest that both VEGFR-1 and VEGFR-2 are involved in stem cell mobilization.

  19. Group Medical Visits (GMVs) in primary care: an RCT of group-based versus individual appointments to reduce HbA1c in older people

    PubMed Central

    Khan, Karim M; Windt, Adriaan; Davis, Jennifer C; Dawes, Martin; Liu-Ambrose, Teresa; Madden, Ken; Marra, Carlo A; Housden, Laura; Hoppmann, Christiane; Adams, David J

    2015-01-01

    Introduction Type 2 diabetes mellitus (T2DM) affects more than 1.1 million Canadians aged ≥65 years. Group Medical Visits are an emerging health service delivery method. Recent systematic reviews show that they can significantly reduce glycated haemoglobin (HbA1c) levels, but Group Visits have not been evaluated within primary care. We intend to determine the clinical effectiveness, quality of life and economic implications of Group Medical Visits within a primary care setting for older people with T2DM. Methods and analysis A 2-year proof-of-concept, single-blinded (measurement team) randomised control trial to test the efficacy of Group Medical Visits in an urban Canadian primary care setting. Participants ≥65 years old with T2DM (N=128) will be equally randomised to either eight groups of eight patients each (Group Medical Visits; Intervention) or to Individual visits (Standard Care; Controls). Those administering cointerventions are not blinded to group assignment. Our sample size is based on estimates of variance (±1.4% for HbA1c) and effect size (0.9/1.4=0.6) from the literature and from our own preliminary data. Forty participants per group will provide a β likelihood of 0.80, assuming an α of 0.05. A conservative estimation of an effect size of 0.7/1.4 changes the N in the power calculation to 59 per group. Hence, we aim to enrol 64 participants in each study arm. We will use intention-to-treat analysis and compare mean HbA1c (% glycosylated HbA1c) (primary outcome) of Intervention/Control participants at 12 months, 24 months and 1 year postintervention on selected clinical, patient-rated and economic measures. Trial registration number NCT02002143. PMID:26169803

  20. Activation of mitochondrial function and Hb expression in non-haematopoietic cells by an EPO inducer ameliorates ischaemic diseases in mice

    PubMed Central

    Hsu, Pei-Lun; Horng, Lin-Yea; Peng, Kang-Yung; Wu, Chia-Ling; Sung, Hui-Ching; Wu, Rong-Tsun

    2013-01-01

    Background and Purpose Many organs suffer from ischaemic injuries that reduce their ability to generate sufficient energy, which is required for functional maintenance and repair. Erythropoietin (EPO) ameliorates ischaemic injuries by pleiotropic effects. The aim of this study was to investigate the effect and mechanism of a small molecule EH-201, and found it as a potent EPO inducer and its effect in non-haematopoietic cells for therapeutic potential in ischemic disorders. Experimental Approach Mice kidney slices, primary hepatocytes, primary cardiomyocytes and C2C12 myoblasts were treated with EH-201. The effects of this treatment on EPO, Hb expression and mitochondrial biogenesis were analysed. In vivo, doxorubicin-induced cardiomyopathic mice were treated with EH-201. The mice were subjected to an endurance test, electrocardiography and echocardiography, and a histological examination of the isolated hearts was performed. EH-201 was also administered to cisplatin-induced nephropathic mice. Key Results In non-haematopoietic cells, EH-201 was potent at inducing EPO. EH-201 also stimulated mitochondrial biogenesis and enhanced the expression of Hb by a mechanism dependent on EPO-mediated signalling. In mechanistic studies, using EPO and EPO receptor-neutralizing antibodies, we confirmed that EH-201 enhances EPO-EPOR autocrine activity. EH-201 robustly increased the endurance performance activity of healthy and cardiomyopathic mice during hypoxic stress, enhanced myocardial mitochondrial biogenesis and Hb expression, and also improved cardiac function. EH-201 ameliorated anaemia and renal dysfunction in nephropathic mice. Conclusions and Implications The enhancement and recovery of cellular functions through the stimulation of mitochondrial activity and Hb production in non-haematopoietic cells by an inducer of endogenous EPO has potential as a therapeutic strategy for ischaemic diseases. PMID:23530756

  1. Application of sigma metrics for the assessment of quality assurance using the MQ-2000 PT HbA1c analyzer

    PubMed Central

    Huysal, Kağan; Budak, Yasemin U

    2015-01-01

    Introduction Glycosylated hemoglobin (HbA1c) concentrations measured in clinical chemistry laboratories show large differences between their interlaboratory reported values. Laboratory measurements of quality performance should be based on quantitative data. The sigma metrics model provides an objective method for the assessment of current HbA1c assays and is useful in quality management planning. The aim of our study was to evaluate the analytical performance of the MQ-2000 PT HbA1c analyzer test results in the context of our operating conditions on the sigma scale. Materials and methods The coefficient of variation was determined from the calculated mean and standard deviation evaluated from internal quality control (QC) (N = 168 days) (Shanghai Huachen Biological Reagent Co. Ltd, China) data, and records of external quality data (KBUDEK, İstanbul, Turkey) measured in the period from May to November 2013 were used to determine the bias. The resulting data and total allowable error rate (TEA = 10%) from the Clinical Laboratory Improvement Amendments of 1988 (CLIA’88) were used to calculate the sigma level. Results The calculated coefficient of variations (CVs) at the two levels, normal (QC1 = 36.6 ± 2.38 mmol/mol) and pathological (QC2 = 84.7 ± 2.68 mmol/mol), were 6.5% and 3.1%, respectively. The average bias between the external QC and MQ-2000 PT during the study period was 4.3%. The calculated average sigma value was 1.19. Conclusions The MQ-2000 PT HbA1c is a new analyser in the market; there is need for improvement and the method should be controlled with greater attention to ensure quality. PMID:26527591

  2. Thin wetted film cylindrical flow photo reactor for the degradation of Procion blue H-B dye over TiO2 and ZnO.

    PubMed

    Neelavannan, M G; Basha, C Ahmed

    2011-01-01

    A thin wetted film cylindrical flow reactor was fabricated for photocatalytic oxidation of Procion blue H-B dye in textile washwater with the suspensions of TiO2 and ZnO. The disappearance of colour and organic reduction were studied in terms of the removal of colour and chemical oxygen demand (COD). Operating parameters such as effect of pH, UV irradiation with and without catalyst, initial concentration of dye and effect of flow rate were studied and kinetics of Procion blue H-B dye has been studied over TiO2 and ZnO surfaces. Since adsorption is the prerequisite condition for decolorization/degradation of dye molecules in the presence of heterogeneous catalysis, the Langmuir and Freundlich isotherms were examined to verify the adsorption intensity. The results clearly demonstrated that, the optimum loading of the photocatalyst was found to be 300 and 400 mg/L of TiO2 and ZnO, respectively. The maximum COD reduction efficiency was 68% for TiO2 and 58% for ZnO. On the other hand, the colour removal efficiency was found to be 74% and 69%, respectively for TiO2- and ZnO-assisted systems under optimum conditions. Conclusively, these two semiconductors could degrade Procion blue H-B dye at different time intervals and both isotherms fit well.

  3. MORPHO-KINEMATIC ANALYSIS OF THE POINT-SYMMETRIC, BIPOLAR PLANETARY NEBULAE Hb 5 AND K 3-17, A PATHWAY TO POLY-POLARITY

    SciTech Connect

    Lopez, J. A.; Garcia-Diaz, Ma. T.; Steffen, W.; Riesgo, H.; Richer, M. G. E-mail: tere@astrosen.unam.mx E-mail: hriesgo@astrosen.unam.mx

    2012-05-10

    The kinematics of the bipolar planetary nebulae Hb 5 and K 3-17 are investigated in detail by means of a comprehensive set of spatially resolved high spectral resolution, long-slit spectra. Both objects share particularly interesting characteristics, such as a complex filamentary, rosette-type nucleus, axial point-symmetry, and very fast bipolar outflows. The kinematic information of Hb 5 is combined with Hubble Space Telescope imagery to construct a detailed three-dimensional model of the nebula using the code SHAPE. The model shows that the large-scale lobes are growing in a non-homologous way. The filamentary loops in the core are proven to actually be secondary lobes emerging from what appears to be a randomly punctured, dense, gaseous core and the material that forms the point-symmetric structure flows within the lobes with a distinct kinematic pattern and its interaction with the lobes has had a shaping effect on them. Hb 5 and K 3-17 may represent a class of fast evolving planetary nebulae that will develop poly-polar characteristics once the nebular core evolves and expands.

  4. [HbA1c is not enough in screening for impaired glucose metabolism. Glucose tolerance tests are also needed, as shown in Swedish prospective epidemiological study].

    PubMed

    Hellgren, Margareta; Daka, Bledar; Larsson, Charlotte

    2015-09-29

    An HbA1c threshold of ≥ 42 mmol/mol has been proposed to diagnose prediabetes. The sensitivity, specificity and positive predictive value of the proposed threshold for detection of individuals with prediabetes was examined in a study of 573 randomly selected individuals from Vara and Skövde. In addition, the utility of the FINDRISC questionnaire and of a fasting glucose test in combination with three short questions concerning BMI, heredity for type 2 diabetes and known hypertension was examined. Results from an oral glucose tolerance test were used as reference. The sensitivity of HbA1c and FINDRISC to detect individuals with IGT was 16 and 26 per cent respectively. Questions regarding BMI, heredity and hypertension together with a fasting glucose test yielded a sensitivity of 50%, but a lower specificity and positive predictive value. We conclude that HbA1c inefficiently detected individuals with impaired glucose tolerance and that oral glucose tolerance tests can still preferably be recommended.

  5. Epidermal Hyperplasia and Elevated HB-EGF are More Prominent in Retinoid Dermatitis Compared with Irritant Contact Dermatitis Induced by Benzalkonium Chloride

    PubMed Central

    Lee, Jung Eun; Chang, Jae Yong; Lee, Sang Eun; Kim, Moon Young; Lee, Jeong Seon; Lee, Min Geol

    2010-01-01

    Background 'Retinoid dermatitis' is a retinoid-induced irritant contact dermatitis (ICD). The mechanism of retinoid dermatitis may be different from that of other ICDs. However, it remains uncertain how topical retinoid induce ICD. Objective We compared several aspects of contact dermatitis induced by topical retinol and benzalkonium chloride (BKC) on hairless mice skin. Methods 2% retinol or 2.5% BKC was applied to hairless mice and transepidermal water loss (TEWL), ear thickness, histologic and immunohistochemical findings were compared. We also compared mRNA expression of inflammatory cytokines, epidermal differential markers, cyclooxygenases (COXs) and heparin binding epidermal growth factor like growth factor (HB-EGF). Results Topical application of 2% retinol and 2.5% BKC increased TEWL and ear thickness in similar intensity. Epidermal hyperplasia was more prominent in retinol treated skin. Proliferating cell nuclear antigen, involucrin and loricrin expression were higher in retinol-treated skin than in BKC-treated skin. Filaggrin, however, was more expressed in BKC-treated skin. The mRNA expression of IL-8, TNF-α, COX-2, involucrin, loricrin and filaggrin were increased in both retinol- and BKC-treated skin in similar intensity. HB-EGF was more significantly increased in retinol-treated skin. Conclusion Elevated HB-EGF and epidermal hyperplasia are more prominent features of retinoid dermatitis than in BKC-induced ICD. PMID:20711265

  6. Hot HB Stars in Globular Clusters: Physical Parameters and Consequences for Theory. VI; The Second Parameter Pair M 3 and M 13

    NASA Technical Reports Server (NTRS)

    Moehler, S.; Landsman, W. B.; Sweigart, A. V.; Grundahl, F.

    2003-01-01

    We present the results of spectroscopic analyses of hot horizontal branch (HB) stars in M 13 and M 3, which form a famous "second parameter" pair. F rom the spectra and Stromgren photometry we derived - for the first time in M 13 - atmospheric parameters (effective temperature and surface gravity). For stars with Stromgren temperatures between 10,000 and 12,000 K we found excellent agreement between the atmospheric parameters derived from Stromgren photometry and those derived from Balmer line profile fits. However, for cooler stars there is a disagreement in the parameters derived by the two methods, for which we have no satisfactory explanation. Stars hotter than 12,000 K show evidence for helium depletion and iron enrichment, both in M 3 and M 13. Accounting for the iron enrichment substantially improves the agreement with canonical evolutionary models, although the derived gravities and masses are still somewhat too low. This remaining discrepancy may be an indication that scaled-solar metal-rich model atmospheres do not adequately represent the highly non-solar abundance ratios found in blue HB stars affected by diffusion. We discuss the effects of an enhancement in the envelope helium abundance on the atmospheric parameters of the blue HB stars, as might be caused by deep mixing on the red giant branch or primordial pollution from an earlier generation of intermediate mass asymptotic giant branch stars. Key words. Stars: atmospheres - Stars: evolution - Stars: horizontal branch - Globular clusters: individual: M 3 - Globular clusters: individual: M 13

  7. Immunogenicity and reactogenicity of HbOC vaccine administered simultaneously with acellular pertussis vaccine (DTaP) into either arms or thighs of infants.

    PubMed

    Schmitt, H J; Wirsing von König, C H; Zepp, F; Huff, J; Jahn, K; Schmidtke, P; Meyer, C; Habermehl, P; Uhlenbusch, R; Angersbach, P

    1997-01-01

    To evaluate the reactogenicity and immunogenicity of a Haemophilus influenzae type b conjugate vaccine (HbOC) and of a tricomponent acellular pertussis vaccine (DTaP) when injected simultaneously into either contralateral arms or into contralateral thighs, 110 infants were enrolled to receive three doses of DTaP at 3, 4, and 5 months and two HbOC doses at 3 and 5 months of age. Administration of either of the two vaccines into arms was associated with significantly more local side effects than administration into thighs. There was no difference in geometric mean concentration (GMC) values for any of the four vaccine antigens between subjects who had been vaccinated into arms or thighs. After immunization, all children had protective antibody titers to diphtheria toxin. While post vaccination the mean anti-tetanus toxoid GMC was > or = 1.25 IU/ml, there was no significant rise as compared to the GMC before vaccination. GMCs of antibodies against the various pertussis antigens were similar to those observed before with the same DTaP vaccine. The simultaneous administration of DTaP and HbOC was safe and immunogenic irrespective of the site of vaccine administration, but significantly more local reactions occurred when vaccines were injected into arms.

  8. Medication Adherence Mediates the Association between Type D Personality and High HbA1c Level in Chinese Patients with Type 2 Diabetes Mellitus: A Six-Month Follow-Up Study

    PubMed Central

    Li, Xuemei; Gao, Min; Zhang, Shengfa; Xu, Huiwen; Zhou, Huixuan; Wang, Xiaohua; Qu, Zhiyong; Guo, Jing

    2017-01-01

    Aims. To examine the association between Type D personality and HbA1c level and to explore the mediating role of medication adherence between them in patients with type 2 diabetes mellitus (T2DM). Methods. 330 patients went on to complete a self-report measure of medication adherence and the HbA1c tests. Chi-square test, T test, Ordinary Least Square Regression (OLS), and Recentered Influence Function Regression (RIF) were employed. Results. Patients with Type D personality had significantly higher HbA1c value (P < 0.01). When Type D personality was operationalized as a categorical variable, SI was associated with HbA1c (P < 0.01). When NA, SI, and their interaction term were entered into regression, all of them were no longer associated with HbA1c level (P > 0.1). On the other hand, when Type D personality was operationalized as a continuous variable, only SI trait was associated with HbA1c level (P < 0.01). When NA, SI, and NA × SI term together were entered into regression, only SI was not related to HbA1c level. Furthermore, medication adherence had a significant mediation effect between Type D personality and HbA1c, accounting for 54.43% of the total effect. Conclusion. Type D personality was associated with HbA1c in direct and indirect ways, and medication adherence acted as a mediator role. PMID:28280745

  9. Erythrocytosis in a child due to Hb Andrew-Minneapolis [β144(HC1)Lys→Asn (AAG>AAT or AAC)] associated with a Spanish (δβ)(0)-thalassemia.

    PubMed

    Ropero, Paloma; González, Fernando A; Cela, Elena; Beléndez, Cristina; Pérez, Beatriz; Seri, Cristina; Fontanes, Emilia; Villegas, Ana; Díaz-Mediavilla, Joaquin

    2013-01-01

    We report a rare association of δβ-thalassemia (δβ-thal) and a hemoglobin (Hb) variant with high oxygen affinity in a Spanish newborn. The proband had no Hb A and showed microcytosis and hypochromia; the peripheral blood smear was compatible with a thalassemia trait. Molecular studies revealed that the proband had a Spanish (δβ)(0)-thal (inherited from his father) and also carried a de novo variant (Hb Andrew-Minneapolis) because from the point of hematology, his mother was quite normal. The hemoglobinopathies with high affinity for oxygen constitute an infrequent cause of secondary congenital erythrocytosis. The degree of erythrocytosis and the resulting clinical manifestations are highly variable, depending on the degree of altered oxygen affinity and the presence of thalassemic genes. Thus, when these variants are associated with β(0)- or δβ-thal, as in our case, the proportion of abnormal Hb is ∼100.0%, which may cause polycythemia, hyperviscosity, and iron deficiency. This type of association is very rare and few have been described, especially in children, as they would normally be detected in adults as the increased packed cell volume (PCV) also increases blood viscosity and causes the typical symptoms (cephalalgia, drowsiness, dizziness). The association of a high oxygen affinity Hb and a δβ-thal presents a greater degree of erythrocytosis than when this same variant is associated with a β(0)-thal, mainly because the Hb F percentage is usually greater in the δβ-thal, and Hb F normally shows a greater affinity for oxygen and a reduced P(50), although one must always take into account the degree of oxygen affinity of the Hb variant. Familial erythrocytosis and an abnormal electrophoresis finding are indicative of a high affinity Hb. However, the absence of these findings does not reject the possibility of hemoglobinopathies, and in these cases, functional and molecular studies would be justified and should be mandatory for the differential

  10. PROGENS-HbA1c study: safety and effectiveness of premixed recombinant human insulin (Gensulin M30)

    PubMed Central

    Walicka, Magdalena; Jóźwiak, Jacek; Rzeszotarski, Jacek; Zarzycka-Lindner, Grażyna; Zonenberg, Anna; Bijoś, Paweł; Masierek, Małgorzata

    2016-01-01

    Introduction Insulin analogues have gained widespread popularity. However, in many countries the use of these drugs is limited by their relatively high cost, so there is still a need for more cost-effective human insulin therapies. The aim of the study was to assess the effectiveness and safety of the premixed recombinant human insulin (rhuI) Gensulin M30 in a real-life setting. Material and methods The study group consisted of 4257 patients (2196 female, 2061 male) with type 2 diabetes, aged 63.7 ±9.4, with body mass index (BMI) 30.3 ±4.5 kg/m2 and diabetes duration 9 ±5.5 years. All patients were treated with premixed rhuI Gensulin M30. In 91.7% of patients, insulin was used in combination with metformin. In 3.7% of patients, it was used with sulphonylureas. The patients were observed for a period of 6 months. Results The total insulin dose on visit 1 was 36.1 ±18.7 U (0.42 ±0.22 U/kg), and by the end of the study it reached 40.3 ±18.9 U (0.48 ±0.22 U/kg). A significant, continuous decrease of the levels of glycated hemoglobin (HbA1c), along with fasting and postprandial plasma glucose, was observed during the study period. The frequency of hypoglycemia increased slightly during the study, although these figures remained low, especially with regard to severe hypoglycemic episodes (0.02 episodes/patient/year). The lowest number of hypoglycemic episodes occurred in patients treated with insulin and metformin, while the highest number of episodes was observed in patients treated with insulin alone. No weight changes were noted in the patients during the study. Conclusions This study shows rhuI Gensulin M30 to be effective and safe in a real-life setting. PMID:27695488

  11. Molecular Dynamics of a Thermostable Multicopper Oxidase from Thermus thermophilus HB27: Structural Differences between the Apo and Holo Forms

    PubMed Central

    Bello, Martiniano; Valderrama, Brenda; Serrano-Posada, Hugo; Rudiño-Piñera, Enrique

    2012-01-01

    Molecular dynamic (MD) simulations have been performed on Tth-MCO, a hyperthermophilic multicopper oxidase from thermus thermophilus HB27, in the apo as well as the holo form, with the aim of exploring the structural dynamic properties common to the two conformational states. According to structural comparison between this enzyme and other MCOs, the substrate in process to electron transfer in an outer-sphere event seems to transiently occupy a shallow and overall hydrophobic cavity near the Cu type 1 (T1Cu). The linker connecting the β-strands 21 and 24 of the second domain (loop (β21–β24)D2) has the same conformation in both states, forming a flexible lid at the entrance of the electron-transfer cavity. Loop (β21–β24)D2 has been tentatively assigned a role occluding the access to the electron-transfer site. The dynamic of the loop (β21–β24)D2 has been investigated by MD simulation, and results show that the structures of both species have the same secondary and tertiary structure during almost all the MD simulations. In the simulation, loop (β21–β24)D2 of the holo form undergoes a higher mobility than in the apo form. In fact, loop (β21–β24)D2 of the holo form experiences a conformational change which enables exposure to the electron-transfer site (open conformation), while in the apo form the opposite effect takes place (closed conformation). To confirm the hypothesis that the open conformation might facilitate the transient electron-donor molecule occupation of the site, the simulation was extended another 40 ns with the electron-donor molecule docked into the protein cavity. Upon electron-donor molecule stabilization, loops near the cavity reduce their mobility. These findings show that coordination between the copper and the protein might play an important role in the general mobility of the enzyme, and that the open conformation seems to be required for the electron transfer process to T1Cu. PMID:22808237

  12. Concomitant administration of a fully liquid, ready-to-use DTaP-IPV-HB-PRP-T hexavalent vaccine with a meningococcal serogroup C conjugate vaccine in infants.

    PubMed

    Vesikari, Timo; Borrow, Ray; Da Costa, Xavier; Richard, Patrick; Eymin, Cécile; Boisnard, Florence; Lockhart, Stephen

    2017-01-11

    DTaP-IPV-HB-PRP-T or hexavalent vaccines are indicated for primary and booster vaccination of infants and toddlers against diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and invasive diseases caused by Haemophilus influenzae type b (Hib). The present study evaluates the safety and immunogenicity of a ready-to-use hexavalent vaccine when co-administered with a meningococcal serogroup C conjugate (MenC) vaccine in infants. This was a phase III, open-label, randomised, multicentre study conducted in Finland. Healthy infants, aged 46-74days (n=350), were randomised in a ratio of 1:1 to receive DTaP-IPV-HB-PRP-T vaccine at two, three and four months, either with a MenC vaccine co-administered at two and four months (Group 1; n=175) or without MenC vaccine (Group 2; n=175). All infants also received routine rotavirus and 13-valent pneumococcal conjugate vaccines. The proportion of participants with an anti-HBs concentration ⩾10mIU/mL assessed one month after the third dose of DTaP-IPV-HB-PRP-T vaccine was 97.5% [95%CI: 93.1-99.3] in the coadministration group and 96.1% [95%CI: 91.8-98.6] in the group without MenC vaccine. The proportion of participants with an anti-MenC SBA titre ⩾8 assessed one month after the second dose of MenC vaccine was 100% in the coadministration group. Both primary objectives were achieved. Secondary immunogenicity and safety analyses showed that co-administration of DTaP-IPV-HB-PRP-T and MenC vaccines did not impact the immune response to the antigens of each of the two vaccines. All vaccines were well tolerated and the safety profile of DTaP-IPV-HB-PRP-T vaccine was similar in both groups. ClinicalTrials.gov identifier: NCT01839175; EudraCT number: 2012-005547-24.

  13. Pretreatment with pPolyHb attenuates H2O2-induced endothelial cell injury through inhibition of JNK/p38 MAPK pathway by upregulation of heme oxygenase-1.

    PubMed

    Xue, Haiyan; Yan, Kunping; Zhao, Xiufang; Zhu, Wenjin; Liu, Lijun; Xie, Zhilan; Zhu, Hongli; Chen, Chao

    2015-06-01

    Polymerized porcine hemoglobin (pPolyHb) exhibits a protective effect on ischemia/reperfusion of organ grafts. A series of experiments were performed to explore the underlying cytoprotective mechanisms of pPolyHb pretreatment on H2O2-induced cell death and apoptosis. The results showed that the pretreatment augmented heme oxygenase-1 (HO-1) expression, and at the same time, decreased the phosphorylation of JNK/p38 mitogen-activated protein kinase (MAPK) and intracellular ROS generation in H2O2-treated HUVECs. Moreover, the inhibition of HO-1 expression by tin porphyrin (SnPP) abolished the protective effects of pPolyHb, which suggested that the cytoprotective effect of pPolyHb involves upregulating HO-1 and subsequently decreasing the phosphorylation of the JNK and p38 MAPK and ROS generation.

  14. The influence of sample freezing at – 80 °C for 2–12 weeks on glycated haemoglobin (HbA1c) concentration assayed by HPLC method on Bio-Rad D-10® auto analyzer

    PubMed Central

    Bergmann, Katarzyna; Sypniewska, Grazyna

    2016-01-01

    Introduction The aim of the study was to evaluate the effect of a single freeze/thaw cycle on HbA1c concentrations measured by commercially available HPLC method. Materials and methods Study included 128 whole blood samples collected from diabetic patients (N = 60) and healthy volunteers (N = 68). HbA1c concentrations were measured in fresh blood samples. Then samples were frozen at - 80 °C for up to 12 weeks. HbA1c was assayed by ion-exchange HPLC method on Bio-Rad D-10® analyzer. Variables were compared using Wilcoxon and ANOVA Kruskal-Wallis tests. Bias between HbA1c measured in fresh and frozen samples was calculated. The comparability of HbA1c concentrations was assessed by Bland-Altman plot. Results Median (IQR) HbA1c concentration was 45.3 (36.6–61.2) mmol/mol for fresh and 45.3 (36.6–60.6) mmol/mol for frozen/thawed samples. No significant difference in HbA1c concentrations was found comparing fresh and frozen/thawed samples (P = 0.070) in the whole group, as well as in healthy and diabetic subjects. The median calculated bias between fresh and frozen/thawed samples was 0% in whole group and healthy subjects, and 1.19% in diabetic patients. No significant difference was found between the biases according to baseline HbA1c values (P = 0.150). The Bland-Altman plot analysis showed a positive bias of 0.4% (95% CI: - 2.8 - 3.7%), which indicates high compliance between HbA1c values and no relevant influence of sample freezing on clinical significance of HbA1c measurement. Conclusions Storage for up to 12 weeks at – 80 °C with a single freeze/thaw cycle does not affect HbA1c concentrations measured with HPLC method on Bio-Rad D-10® analyzer. PMID:27812303

  15. The Complete Sequences and Ecological Roles of Two IncP-1β Plasmids, pHB44 and pBS64, Isolated from the Mycosphere of Laccaria proxima.

    PubMed

    Zhang, Miaozhi; Brons, Jolanda K; van Elsas, Jan Dirk

    2016-01-01

    Two novel plasmids, coined pHB44 and pBS64, were recently found in Variovorax paradoxus strains HB44 and BS64 isolated from the mycosphere of Laccaria proxima, on two different sampling occasions. We here describe the full sequences of pHB44 and pBS64 and establish their evolutionary placement and ecological function. Both plasmids, unique for mycospheric V. paradoxus, were around 58 kb in size. They possessed, in a very similar fashion, three main plasmid backbone regions, which were predicted to be involved in plasmid replication, central control of maintenance, and conjugational transfer. Phylogenetic inference on the basis of seven selected and concatenated plasmid backbone genes provided solid evidence for the placement of the two plasmids in the IncP-1β1 group, with the recently isolated IncP-1β1 plasmid pMBUI8 as the closest relative. A comparative analysis of the sequences present in each of the recombinational hot spots (RHS) I to III across plasmids pHB44, pBS64, and pMBUI8 revealed the insertions found in plasmids pHB44 and pBS64 to be different from those of pMBUI8. Whereas, in the former two plasmids, RHS I and III were devoid of any major inserts, their RHS II regions contained inserts of 15,043 (pHB44) and 16,406 kb (pBS64), against about 9,3 kb for pMBUI8. Interestingly, these regions were highly similar across plasmids pHB44 and pBS64, and differed from that of pMBUI8. Closer inspection revealed the insert in the former plasmids to contain, next to transposases, an "mmf" gene cassette previously reported to encode metal "responsiveness" in the PromA plasmid pMOL98. Whereas the plasmid pHB44 RHS II contained the canonical mmf sequence, that in pBS64 contained, in addition, a "two-gene duplicated region" flanking the mmf C2 gene. In vitro experiments on the growth and survival of strains with or without plasmid pHB44 suggested this plasmid was involved in the binding and import of Fe(3+) as well as V(3+) ions into the host cells, thus yielding a

  16. Regulation of HbPIP2;3, a Latex-Abundant Water Transporter, Is Associated with Latex Dilution and Yield in the Rubber Tree (Hevea brasiliensis Muell. Arg.)

    PubMed Central

    Cai, Xiuqing; Wang, Jin; Rookes, James; Lin, Weifu; Cahill, David; Kong, Lingxue

    2015-01-01

    Rubber tree (Hevea brasiliensis) latex, the source of natural rubber, is synthesised in the cytoplasm of laticifers. Efficient water inflow into laticifers is crucial for latex flow and production since it is the determinant of the total solid content of latex and its fluidity after tapping. As the mature laticifer vessel rings are devoid of plasmodesmata, water exchange between laticifers and surrounding cells is believed to be governed by plasma membrane intrinsic proteins (PIPs). To identify the most important PIP aquaporin in the water balance of laticifers, the transcriptional profiles of ten-latex-expressed PIPs were analysed. One of the most abundant transcripts, designated HbPIP2;3, was characterised in this study. When tested in Xenopus laevis oocytes HbPIP2;3 showed a high efficiency in increasing plasmalemma water conductance. Expression analysis indicated that the HbPIP2;3 gene was preferentially expressed in latex, and the transcripts were up-regulated by both wounding and exogenously applied Ethrel (a commonly-used ethylene releaser). Although regular tapping up-regulated the expression of HbPIP2;3 during the first few tappings of the virginal rubber trees, the transcriptional kinetics of HbPIP2;3 to Ethrel stimulation in the regularly tapped tree exhibited a similar pattern to that of the previously reported HbPIP2;1 in the virginal rubber trees. Furthermore, the mRNA level of HbPIP2;3 was associated with clonal yield potential and the Ethrel stimulation response. Together, these results have revealed the central regulatory role of HbPIP2;3 in laticifer water balance and ethylene stimulation of latex production in Hevea. PMID:25927524

  17. Single, community-based blood glucose readings may be a viable alternative for community surveillance of HbA1c and poor glycaemic control in people with known diabetes in resource-poor settings

    PubMed Central

    Reidpath, Daniel D.; Jahan, Nowrozy K.; Mohan, Devi; Allotey, Pascale

    2016-01-01

    Background The term HbA1c (glycated haemoglobin) is commonly used in relation to diabetes mellitus. The measure gives an indication of the average blood sugar levels over a period of weeks or months prior to testing. For most low- and middle-income countries HbA1c measurement in community surveillance is prohibitively expensive. A question arises about the possibility of using a single blood glucose measure for estimating HbA1c and therefore identifying poor glycaemic control in resource-poor settings. Design Using data from the 2011–2012 US National Health and Nutrition Examination Surveys, we examined the relationship between HbA1c and a single fasting measure of blood glucose in a non-clinical population of people with known diabetes (n=333). A linear equation for estimating HbA1c from blood glucose was developed. Appropriate blood glucose cut-off values were set for poor glycaemic control (HbA1c≥69.4 mmol/mol). Results The HbA1c and blood glucose measures were well correlated (r=0.7). Three blood glucose cut-off values were considered for classifying poor glycaemic control: 8.0, 8.9, and 11.4 mmol/L. A blood glucose of 11.4 had a specificity of 1, but poor sensitivity (0.37); 8.9 had high specificity (0.94) and moderate sensitivity (0.7); 8.0 was associated with good specificity (0.81) and sensitivity (0.75). Conclusions Where HbA1c measurement is too expensive for community surveillance, a single blood glucose measure may be a reasonable alternative. Generalising the specific results from these US data to low resource settings may not be appropriate, but the general approach is worthy of further investigation. PMID:27511810

  18. Regulation of HbPIP2;3, a Latex-Abundant Water Transporter, Is Associated with Latex Dilution and Yield in the Rubber Tree (Hevea brasiliensis Muell. Arg.).

    PubMed

    An, Feng; Zou, Zhi; Cai, Xiuqing; Wang, Jin; Rookes, James; Lin, Weifu; Cahill, David; Kong, Lingxue

    2015-01-01

    Rubber tree (Hevea brasiliensis) latex, the source of natural rubber, is synthesised in the cytoplasm of laticifers. Efficient water inflow into laticifers is crucial for latex flow and production since it is the determinant of the total solid content of latex and its fluidity after tapping. As the mature laticifer vessel rings are devoid of plasmodesmata, water exchange between laticifers and surrounding cells is believed to be governed by plasma membrane intrinsic proteins (PIPs). To identify the most important PIP aquaporin in the water balance of laticifers, the transcriptional profiles of ten-latex-expressed PIPs were analysed. One of the most abundant transcripts, designated HbPIP2;3, was characterised in this study. When tested in Xenopus laevis oocytes HbPIP2;3 showed a high efficiency in increasing plasmalemma water conductance. Expression analysis indicated that the HbPIP2;3 gene was preferentially expressed in latex, and the transcripts were up-regulated by both wounding and exogenously applied Ethrel (a commonly-used ethylene releaser). Although regular tapping up-regulated the expression of HbPIP2;3 during the first few tappings of the virginal rubber trees, the transcriptional kinetics of HbPIP2;3 to Ethrel stimulation in the regularly tapped tree exhibited a similar pattern to that of the previously reported HbPIP2;1 in the virginal rubber trees. Furthermore, the mRNA level of HbPIP2;3 was associated with clonal yield potential and the Ethrel stimulation response. Together, these results have revealed the central regulatory role of HbPIP2;3 in laticifer water balance and ethylene stimulation of latex production in Hevea.

  19. Health Coaching Reduces HbA1c in Type 2 Diabetic Patients From a Lower-Socioeconomic Status Community: A Randomized Controlled Trial

    PubMed Central

    Wayne, Noah; Perez, Daniel F; Kaplan, David M

    2015-01-01

    Background Adoptions of health behaviors are crucial for maintaining good health after type 2 diabetes mellitus (T2DM) diagnoses. However, adherence to glucoregulating behaviors like regular exercise and balanced diet can be challenging, especially for people living in lower-socioeconomic status (SES) communities. Providing cost-effective interventions that improve self-management is important for improving quality of life and the sustainability of health care systems. Objective To evaluate a health coach intervention with and without the use of mobile phones to support health behavior change in patients with type 2 diabetes. Methods In this noninferiority, pragmatic randomized controlled trial (RCT), patients from two primary care health centers in Toronto, Canada, with type 2 diabetes and a glycated hemoglobin/hemoglobin A1c (HbA1c) level of ≥7.3% (56.3 mmol/mol) were randomized to receive 6 months of health coaching with or without mobile phone monitoring support. We hypothesized that both approaches would result in significant HbA1c reductions, although health coaching with mobile phone monitoring would result in significantly larger effects. Participants were evaluated at baseline, 3 months, and 6 months. The primary outcome was the change in HbA1c from baseline to 6 months (difference between and within groups). Other outcomes included weight, waist circumference, body mass index (BMI), satisfaction with life, depression and anxiety (Hospital Anxiety and Depression Scale [HADS]), positive and negative affect (Positive and Negative Affect Schedule [PANAS]), and quality of life (Short Form Health Survey-12 [SF-12]). Results A total of 138 patients were randomized and 7 were excluded for a substudy; of the remaining 131, 67 were allocated to the intervention group and 64 to the control group. Primary outcome data were available for 97 participants (74.0%). While both groups reduced their HbA1c levels, there were no significant between-group differences in

  20. Real-time evaluation of tissue vitality by monitoring of microcirculatory blood flow, HbO2, and mitochondrial NADH redox state

    NASA Astrophysics Data System (ADS)

    Deutsch, Assaf; Pevzner, Eliyahu; Jaronkin, Alex; Mayevsky, Avraham

    2004-06-01

    Monitoring of tissue vitality (oxygen supply/demand) in real time is very rare in clinical practice although its use as an early warning alarming system, for clinical care medicine, is very practical. In our previous communication (SPIE 2003) we described the Tissue Spectroscope - TiSpec02, by which tissue microcirculatory blood flow (TBF) and mitochondrial NADH fluorescence were measured using a single light source (390nm). In order to improve the measurement capabilities as well as to decrease dramatically the size and cost of this clinical device, we have changed the TiSpec02 into a multi-wavelength illumination system in the new TiSpec03. In order to measure microcirculatory blood flow by laser Doppler flowmetry we used a 785nm laser diode. For mitochondrial NADH fluorescence measurement we adopted the 370nm LED. For the determination of the oxygenation level of hemoglobin (HbO2) we used the 2-wavelength reflectance technique. This new monitored parameter that was added to the TiSpec03 increases the accuracy of the diagnosis of tissue vitality. The bundle of optical fibers used to connect the tissue to the TiSpec03, was integrated into a special anchoring methodology depending on the monitored tissue or organ. In order to test the performance of the improved TiSpec we have used it in experimental animals brain models exposed to various pathophysiological conditions. Rats and gerbils were anesthetized and the fiber optic probe was located epidurally used dental acrylic cement. During anoxia and ischemia the lack of O2 led to a clear decrease in TBF and HbO2 while NADH shows a large elevation. When brain activation was induced by cortical spreading depression (SD), the elevated O2 consumption was recorded as a large oxidation (decrease) of mitochondrial NADH while TBF increase dramatically. Blood HbO2 was not affected significantly by the SD wave.

  1. Changes in HbA1c and circulating and adipose tissue androgen levels in overweight‐obese women with polycystic ovary syndrome in response to electroacupuncture

    PubMed Central

    Maliqueo, M.; Soligo, M.; Protto, V.; Manni, L.; Jerlhag, E.; Kokosar, M.; Sazonova, A.; Behre, C. J.; Lind, M.; Ohlsson, C.; Højlund, K.; Benrick, A.

    2016-01-01

    Summary Aim Insulin sensitivity is ~40% lower in women with polycystic ovary syndrome (PCOS) than in controls. We tested the hypothesis that 5 weeks of electroacupuncture treatment improves glucose regulation and androgen levels in overweight/obese women with PCOS. Material and Methods Seventeen women with PCOS, aged 18 to 38 years, with a body mass index (BMI) ≥25 kg/m2 and diagnosed with PCOS were included in this experimental and feasibility study and subjected to five weeks of electroacupuncture treatments three times/week. The primary outcome was changes in whole‐body glucose homeostasis measured by euglycemic hyperinsulinemic clamp before and after the intervention. Secondary outcome were changes in HbA1c, circulating catecholamines, adipocyte size and adipose tissue expression of sex steroids and nerve growth factor (NGF). Results No significant change in glucose homeostasis was observed, but HbA1c decreased by 9.5% (p = 0.004), circulating testosterone decreased by 22% (p = 0.0007) and dihydrotestosterone decreased by 12% (p = 0.007). The two vagal activity markers of plasma serotonin levels and the dopamine metabolite homovanillic acid decreased by 21% (p = 0.027) and 20% (p = 0.011), respectively. Adipose tissue concentrations of testosterone decreased by 18% (p = 0.049), and androstenedione decreased by 13% (p = 0.035), and mature NGF/proNGF ratio, a marker of sympathetic activity, increased (p = 0.04). These changes occurred without changes in anthropometrics. Conclusion Five weeks of electroacupuncture treatment improves HbA1c and circulating and adipose tissue androgens in women with PCOS. This effect is mediated, at least in part, via modulation of vagal activity and adipose tissue sympathetic activity. Based on these findings, we have recently initiated a randomized controlled study (NTC02647827). PMID:28090348

  2. Antiproliferative activity of goniothalamin enantiomers involves DNA damage, cell cycle arrest and apoptosis induction in MCF-7 and HB4a cells.

    PubMed

    Semprebon, Simone Cristine; Marques, Lilian Areal; D'Epiro, Gláucia Fernanda Rocha; de Camargo, Elaine Aparecida; da Silva, Glenda Nicioli; Niwa, Andressa Megumi; Macedo Junior, Fernando; Mantovani, Mário Sérgio

    2015-12-25

    (R)-goniothalamin (R-GNT) is a styryl lactone that exhibits antiproliferative property against several tumor cell lines. (S)-goniothalamin (S-GNT) is the synthetic enantiomer of R-GNT, and their biological properties are poorly understood. The aim of this study was to evaluate the antiproliferative mechanisms of (R)-goniothalamin and (S)-goniothalamin in MCF-7 breast cancer cells and HB4a epithelial mammary cells. To determine the mechanisms of cell growth inhibition, we analyzed the ability of R-GNT and S-GNT to induce DNA damage, cell cycle arrest and apoptosis. Moreover, the gene expression of cell cycle components, including cyclin, CDKs and CKIs, as well as of genes involved in apoptosis and the DNA damage response were evaluated. The natural enantiomer R-GNT proved more effective in both cell lines than did the synthetic enantiomer S-GNT, inhibiting cell proliferation via cell cycle arrest and apoptosis induction, likely in response to DNA damage. The cell cycle inhibition caused by R-GNT was mediated through the upregulation of CIP/KIP cyclin-kinase inhibitors and through the downregulation of cyclins and CDKs. S-GNT, in turn, was able to cause G0/G1 cell cycle arrest and DNA damage in MCF-7 cells and apoptosis induction only in HB4a cells. Therefore, goniothalamin presents potent antiproliferative activity to breast cancer cells MCF-7. However, exposure to goniothalamin brings some undesirable effects to non-tumor cells HB4a, including genotoxicity and apoptosis induction.

  3. Nano/micro hybrid scaffold of PCL or P3HB nanofibers combined with silk fibroin for tendon and ligament tissue engineering.

    PubMed

    Naghashzargar, Elham; Farè, Silvia; Catto, Valentina; Bertoldi, Serena; Semnani, Dariush; Karbasi, Saeed; Tanzi, Maria Cristina

    2015-07-04

    A novel biodegradable nano/micro hybrid structure was obtained by electrospinning P3HB or PCL nanofibers onto a twisted silk fibroin (SF) structure, with the aim of fabricating a suitable scaffold for tendon and ligament tissue engineering. The electrospinning (ES) processing parameters for P3HB and PCL were optimized on 2D samples, and applied to produce two different nano/micro hybrid constructs (SF/ES-PCL and SF/ES-P3HB).Morphological, chemico-physical and mechanical properties of the novel hybrid scaffolds were evaluated by SEM, ATR FT-IR, DSC, tensile and thermodynamic mechanical tests. The results demonstrated that the nanofibers were tightly wrapped around the silk filaments, and the crystallinity of the SF twisted yarns was not influenced by the presence of the electrospun polymers. The slightly higher mechanical properties of the hybrid constructs confirmed an increase of internal forces due to the interaction between nano and micro components. Cell culture tests with L929 fibroblasts, in the presence of the sample eluates or in direct contact with the hybrid structures, showed no cytotoxic effects and a good level of cytocompatibility of the nano/micro hybrid structures in term of cell viability, particularly at day 1. Cell viability onto the nano/micro hybrid structures decreased from the first to the third day of culture when compared with the control culture plastic, but appeared to be higher when compared with the uncoated SF yarns. Although additional in vitro and in vivo tests are needed, the original fabrication method here described appears promising for scaffolds suitable for tendon and ligament tissue engineering.

  4. A theoretical evaluation of the pKHB and DeltaH[symbol: see text]HB hydrogen-bond scales of nitrogen bases.

    PubMed

    Besseau, François; Graton, Jérôme; Berthelot, Michel

    2008-01-01

    The experimental pKHB hydrogen-bond (HB) basicity scale and the corresponding DeltaH[symbol: see text]HB enthalpic scale of nitrogen compounds are extended and analysed in light of simple theoretical descriptors using the B3LYP density functional method and a medium-size basis set (6-31+G(d,p)).The selected training set includes 59 monofunctional unhindered nitrogen bases for which homogeneous and accurate experimental pKHB and DeltaH[symbol: see text]HB data have been determined by means of the association equilibrium of the bases with a reference hydrogen-bond acid, 4-fluorophenol, in CCl4. The three hybridisation states encountered in the nitrogen atom, sp, sp2 and sp3, are equally represented in this data set. A proper estimation of their experimental enthalpy (DeltaH[symbol: see text]HB) is directly attainable from the theoretical enthalpy of the complexation reaction with hydrogen fluoride (DeltaH[symbol: see text](HF)). However, a second parameter is required to calculate with good accuracy the experimental free energy of association represented by pKHB. About 99% of the variance of the pKHB scale is described by a bilinear equation using the minimum electrostatic potential (Vs,min) of the monomer in addition to the interaction energy (D0(HF). The equations are tested for an external set of 99 additional compounds including very different nitrogen bases such as ortho-substituted pyridines, polyazines and azoles.Theoretical calculations give a reliable estimation of hydrogen-bond basicity provided that the populations of the different isomers of the bases are taken into account by using the Boltzmann law, and that a specific halogen-bond interaction with the solvent CCl4 is considered for polybasic molecules.The pKHB scale can thus be extended to important classes of species experimentally inaccessible in CCl4, to polynitrogen compounds and to molecules of biological significance.

  5. Use of SLAM and PVRL4 and identification of pro-HB-EGF as cell entry receptors for wild type phocine distemper virus.

    PubMed

    Melia, Mary M; Earle, John Philip; Abdullah, Haniah; Reaney, Katherine; Tangy, Frederic; Cosby, Sara Louise

    2014-01-01

    Signalling lymphocyte activation molecule (SLAM) has been identified as an immune cell receptor for the morbilliviruses, measles (MV), canine distemper (CDV), rinderpest and peste des petits ruminants (PPRV) viruses, while CD46 is a receptor for vaccine strains of MV. More recently poliovirus like receptor 4 (PVRL4), also known as nectin 4, has been identified as a receptor for MV, CDV and PPRV on the basolateral surface of polarised epithelial cells. PVRL4 is also up-regulated by MV in human brain endothelial cells. Utilisation of PVRL4 as a receptor by phocine distemper virus (PDV) remains to be demonstrated as well as confirmation of use of SLAM. We have observed that unlike wild type (wt) MV or wtCDV, wtPDV strains replicate in African green monkey kidney Vero cells without prior adaptation, suggesting the use of a further receptor. We therefore examined candidate molecules, glycosaminoglycans (GAG) and the tetraspan proteins, integrin β and the membrane bound form of heparin binding epithelial growth factor (proHB-EGF),for receptor usage by wtPDV in Vero cells. We show that wtPDV replicates in Chinese hamster ovary (CHO) cells expressing SLAM and PVRL4. Similar wtPDV titres are produced in Vero and VeroSLAM cells but more limited fusion occurs in the latter. Infection of Vero cells was not inhibited by anti-CD46 antibody. Removal/disruption of GAG decreased fusion but not the titre of virus. Treatment with anti-integrin β antibody increased rather than decreased infection of Vero cells by wtPDV. However, infection was inhibited by antibody to HB-EGF and the virus replicated in CHO-proHB-EGF cells, indicating use of this molecule as a receptor. Common use of SLAM and PVRL4 by morbilliviruses increases the possibility of cross-species infection. Lack of a requirement for wtPDV adaptation to Vero cells raises the possibility of usage of proHB-EGF as a receptor in vivo but requires further investigation.

  6. Use of SLAM and PVRL4 and Identification of Pro-HB-EGF as Cell Entry Receptors for Wild Type Phocine Distemper Virus

    PubMed Central

    Reaney, Katherine; Tangy, Frederic; Cosby, Sara Louise

    2014-01-01

    Signalling lymphocyte activation molecule (SLAM) has been identified as an immune cell receptor for the morbilliviruses, measles (MV), canine distemper (CDV), rinderpest and peste des petits ruminants (PPRV) viruses, while CD46 is a receptor for vaccine strains of MV. More recently poliovirus like receptor 4 (PVRL4), also known as nectin 4, has been identified as a receptor for MV, CDV and PPRV on the basolateral surface of polarised epithelial cells. PVRL4 is also up-regulated by MV in human brain endothelial cells. Utilisation of PVRL4 as a receptor by phocine distemper virus (PDV) remains to be demonstrated as well as confirmation of use of SLAM. We have observed that unlike wild type (wt) MV or wtCDV, wtPDV strains replicate in African green monkey kidney Vero cells without prior adaptation, suggesting the use of a further receptor. We therefore examined candidate molecules, glycosaminoglycans (GAG) and the tetraspan proteins, integrin β and the membrane bound form of heparin binding epithelial growth factor (proHB-EGF),for receptor usage by wtPDV in Vero cells. We show that wtPDV replicates in Chinese hamster ovary (CHO) cells expressing SLAM and PVRL4. Similar wtPDV titres are produced in Vero and VeroSLAM cells but more limited fusion occurs in the latter. Infection of Vero cells was not inhibited by anti-CD46 antibody. Removal/disruption of GAG decreased fusion but not the titre of virus. Treatment with anti-integrin β antibody increased rather than decreased infection of Vero cells by wtPDV. However, infection was inhibited by antibody to HB-EGF and the virus replicated in CHO-proHB-EGF cells, indicating use of this molecule as a receptor. Common use of SLAM and PVRL4 by morbilliviruses increases the possibility of cross-species infection. Lack of a requirement for wtPDV adaptation to Vero cells raises the possibility of usage of proHB-EGF as a receptor in vivo but requires further investigation. PMID:25171206

  7. TECHNICAL BASIS FOR DOE STANDARD 3013 EQUIVALENCY SUPPORTING REDUCED TEMPERATURE STABILIZATION OF OXALATE-DERIVED PLUTONIUM DIOXIDE PRODUCED BY THE HB-LINE FACILITY AT SAVANNAH RIVER SITE

    SciTech Connect

    Duffey, J. M.; Livingston, R. R.; Berg, J. M.; Veirs, D. K.

    2013-02-06

    This report documents the technical basis for determining that stabilizing highpurity PuO{sub 2} derived from oxalate precipitation at the SRS HB-Line facility at a minimum of 625 {degree}C for at least four hours in an oxidizing atmosphere is equivalent to stabilizing at a minimum of 950 {degree}C for at least two hours as regards meeting the objectives of stabilization defined by DOE-STD-3013 if the material is handled in a way to prevent excessive absorption of water.

  8. Environmental assessment operation of the HB-Line facility and frame waste recovery process for production of Pu-238 oxide at the Savannah River Site

    SciTech Connect

    1995-04-01

    The Department of Energy (DOE) has prepared an environmental assessment (EA), DOE/EA-0948, addressing future operations of the HB-Line facility and the Frame Waste Recovery process at the Savannah River Site (SRS), near Aiken, South Carolina. Based on the analyses in the EA, DOE has determined that the proposed action is not a major Federal action significantly affecting the quality of the human environment within the meaning of the National Environmental Policy Act (NEPA) of 1969. Therefore, DOE has concluded that, the preparation of an environmental impact statement is not required, and is issuing this Finding of No Significant Impact.

  9. DPP-4 inhibitor treatment: β-cell response but not HbA1c reduction is dependent on the duration of diabetes

    PubMed Central

    Kozlovski, Plamen; Bhosekar, Vaishali; Foley, James E

    2017-01-01

    Introduction Dipeptidyl peptidase-4 (DPP-4) inhibitors reduce hyperglycemia in patients with type 2 diabetes mellitus (T2DM) by enhancing insulin and suppressing glucagon secretion. Since T2DM is associated with progressive loss of β-cell function, we hypothesized that the DPP-4 inhibitor action to improve β-cell function would be attenuated with longer duration of T2DM. Methods Data from six randomized, placebo-controlled trials of 24 weeks duration, where β-cell response to vildagliptin 50 mg twice daily was assessed, were pooled. In each study, the insulin secretory rate relative to glucose (ISR/G 0–2h) during glucose load (standard meal or oral glucose tolerance test) was assessed at baseline and end of study. The mean placebo-subtracted difference (PSD) in the change in ISR/G 0–2h from baseline for each study was evaluated as a function of age, duration of T2DM, baseline ISR/G 0–2h, glycated hemoglobin (HbA1c), fasting plasma glucose, body mass index, and mean PSD in the change in HbA1c from baseline, using univariate model. Results There was a strong negative association between the PSD in the change from baseline in ISR/G 0–2h and duration of T2DM (r= −0.89, p<0.02). However, there was no association between the PSD in the change from baseline in ISR/G 0–2h and the PSD in the change from baseline in HbA1c (r=0.33, p=0.52). None of the other characteristics were significantly associated with mean PSD change in ISR/G 0–2h. Conclusion These findings indicate that the response of the β-cell, but not the HbA1c reduction, with vildagliptin is dependent on duration of T2DM. Further, it can be speculated that glucagon suppression may become the predominant mechanism via which glycemic control is improved when treatment with a DPP-4 inhibitor, such as vildagliptin, is initiated late in the natural course of T2DM.

  10. Oxidative aromatization of 1,4-dihydropyridines and pyrazolines using HbA-H(2)O(2): An efficient biomimetic catalyst system providing metabolites of drug candidates.

    PubMed

    Kumar, Atul; Maurya, Ram Awatar; Sharma, Siddharth

    2009-08-01

    Human hemoglobin (HbA) efficiently catalyses the oxidative aromatization of 1,4-dihydropyridines (1,4-DHPs) and pyrazolines with hydrogen peroxide in phosphate buffer. The results of the study reveal that the rates of oxidative aromatization of 1,4-DHPs are substituent dependent. Thus, the present study is very useful in understanding the metabolism of 1,4-DHP drugs in liver by cytochrome P450 and designing novel drugs as well as modifying the existing drugs for better pharmacokinetic profile.

  11. An indirect comparison of HbA1c treatment effect with albiglutide and exenatide 2.0 mg QW using the Bucher method

    PubMed Central

    Martin, Alan A; Parks, Daniel

    2016-01-01

    No head-to-head comparisons exist between once-weekly (QW) glucagon-like peptide-1 receptor agonists; accordingly, this indirect comparison was conducted to evaluate the comparative efficacy of QW albiglutide vs QW exenatide. Following a systematic literature search, it was determined that HARMONY 7 and DURATION 6, Phase III trials for albiglutide and exenatide, respectively, were similar in study design and baseline characteristics and included a common comparator arm, making them suitable for an indirect comparison using the Bucher method. The primary endpoint of change from baseline in glycated hemoglobin (HbA1c) with albiglutide 50 mg QW and exenatide 2.0 mg QW was compared and tested for noninferiority. The indirect comparison showed a treatment difference of 0.0% (95% confidence interval: −0.189% to 0.189%) in mean change in HbA1c from baseline, and albiglutide 50 mg was noninferior to exenatide 2.0 mg QW at the noninferiority margin of 0.3%. In the absence of a head-to-head trial, these results can be used in pharmacoeconomic analysis and to inform health technology assessment and clinical decision making. PMID:27274297

  12. C-Peptide Level in Fasting Plasma and Pooled Urine Predicts HbA1c after Hospitalization in Patients with Type 2 Diabetes Mellitus.

    PubMed

    Sonoda, Remi; Tanaka, Kentaro; Kikuchi, Takako; Onishi, Yukiko; Takao, Toshiko; Tahara, Tazu; Yoshida, Yoko; Suzawa, Naoki; Kawazu, Shoji; Iwamoto, Yasuhiko; Kushiyama, Akifumi

    2016-01-01

    In this study, we investigate how measures of insulin secretion and other clinical information affect long-term glycemic control in patients with type 2 diabetes mellitus. Between October 2012 and June 2014, we monitored 202 diabetes patients who were admitted to the hospital of Asahi Life Foundation for glycemic control, as well as for training and education in diabetes management. We measured glycated hemoglobin (HbA1c) six months after discharge to assess disease management. In univariate analysis, fasting plasma C-peptide immunoreactivity (F-CPR) and pooled urine CPR (U-CPR) were significantly associated with HbA1c, in contrast to ΔCPR and C-peptide index (CPI). This association was strongly independent of most other patient variables. In exploratory factor analysis, five underlying factors, namely insulin resistance, aging, sex differences, insulin secretion, and glycemic control, represented patient characteristics. In particular, insulin secretion and resistance strongly influenced F-CPR, while insulin secretion affected U-CPR. In conclusion, the data indicate that among patients with type 2 diabetes mellitus, F-CPR and U-CPR may predict improved glycemic control six months after hospitalization.

  13. Roles of chlorophyllin in cell proliferation and the expression of apoptotic and cell cycle genes in HB4a non-tumor breast cells.

    PubMed

    D Epiro, Gláucia Fernanda Rocha; Semprebon, Simone Cristine; Niwa, Andressa Megumi; Marcarini, Juliana Cristina; Mantovani, Mário Sérgio

    2016-06-01

    Chlorophyllin (Chl) has attracted interest in the scientific community due to its chemopreventive and antimutagenic properties. However, the molecular mechanisms of action of Chl remain unclear. This study assesses the effects on cell proliferation and the expression of genes involved in apoptosis, and the cell cycle in HB4a cells treated with Chl. Chl was cytotoxic and induced apoptosis to HB4a cells at 400 μg/mL. Analysis of gene expression showed that there was a decrease in the mRNA level of BIRC5 and CCNA2 genes involved in apoptosis and cell cycle progression, respectively. The proapoptotic gene BAX and the antiapoptotic genes BCL-2 and BCL-XL were upregulated. The cytotoxicity of Chl has been attributed to increases in the expression of BAX and decreases in the expression of genes involved in the cell cycle, but increases in the expression of anti-apoptotic genes suggests a mechanism for protection from cell death induced by Chl. This study provides important information about mechanisms that protect against or trigger damaging processes in non-tumor cells.

  14. Increased erythropoiesis of beta-thalassaemia/Hb E proerythroblasts is mediated by high basal levels of ERK1/2 activation.

    PubMed

    Wannatung, Tirawat; Lithanatudom, Pathrapol; Leecharoenkiat, Amporn; Svasti, Saovaros; Fucharoen, Suthat; Smith, Duncan R

    2009-09-01

    Beta-thalassaemia is one of the most common inherited anaemias, arising from a partial or complete loss of beta-globin chain synthesis. In severe cases, marked bone marrow erythroid hyperplasia, believed to result from erythropoietin (EPO)-mediated feedback from the anaemic condition is common, however, as yet, no study has investigated EPO-mediated signal transduction in thalassaemic erythroid cells. Using proerythroblasts generated from peripheral blood circulating CD34+ haematopoietic progenitor cells, the activation of the mitogen-activated protein kinase/extracellular signal-regulated kinases (MAPK/ERKs) pathway was examined under conditions of steady state growth, cytokine deprivation and post-EPO stimulation. Levels of cellular cyclic adenosine monophosphate (cAMP) and Ca2+ were determined as was the degree of erythroid expansion. A significantly higher basal level of phosphorylation of ERK1/2 was observed in beta-thalassaemia/Hb E proerythroblasts as compared to normal controls, which was coupled with significantly higher levels of both cAMP and Ca2+. Modulation of either cAMP or Ca2+ or direct inhibition of MAPK/ERK kinase (MEK) reduced basal levels of ERK1/2 phosphorylation, as well as significantly reducing the level of erythroid expansion. These results suggest that, in contrast to current models, hyper proliferation of beta-thalassaemia/Hb E proerythroblasts is an intrinsic process driven by higher basal levels of ERK1/2 phosphorylation resulting from deregulation of levels of cAMP and Ca2+.

  15. [The figure of a nurse educator improves HbA1c levels and lipid profile in patients with type 1 diabetes].

    PubMed

    López-Alegría, Carmen; Núñez-Sánchez, María Ángeles; García-Palacios, María; Santaolalla-Jiménez, Beatriz; Mueses-Dismey, Alexandra; Gómez-Rivas, Pahola; Pérez-Sanz, Antonio; Ortuño-Micol, Dolores; Meoro-Avilés, Amparo Inmaculada

    2013-11-01

    Diabetes education has proved to be an essential tool in the care of patients with type 1 diabetes mellitus. To perform this educational task, the VII Area Murcia East Diabetes Unit, incorporated nurses in advanced diabetes education in the Hospital General Universitario Reina Sofía of Murcia. We carried out a retrospective study, which assessed the performance of these nurses by evaluating the type 1 diabetic patients attending inquiries between 2007 and 2011. We analyzed a total of 179 medical records, of patients with type 1 diabetes mellitus over 11 years, with 103 (52.3%) males and 94 (47.7%) women. Patients had a mean age 38.25 ± 14.02 years and a mean duration of diabetes of 16.22 ± 11.73 years. The initial mean value of HbA1c was 8.49 ± 2.04%. Only 37 (16.2%) of the 197 patients were under 25 at the start of the study. The results showed that the decrease in HbA1c (-0.57 ± 1.80%) was significant after 6 months (p = 0.002) from the first query, reaching values of 7.86 ± 1.39% and remained from that time. Insulin doses were stable throughout the study.

  16. Polyphasic characterization of poly-3-hydroxybutyrate-co-3-hydroxyvalerate (p(HB-co-HV)) metabolizing and denitrifying Acidovorax sp. strains.

    PubMed

    Schloe, K; Gillis, M; Hoste, B; Pot, B; Vancanneyt, M; Mergaert, J; Swings, J; Biedermann, J; Süssmuth, R

    2000-10-01

    For the purpose of denitrification in small drinking water plants, a bacterial mixed population was isolated from a packed bed column bioreactor with poly-3-hydroxybutyrate-co-3-hydroxyvalerate (P(HB-co-HV)) as a substrate for the denitrification of ground water (10 degrees C). Isolates 2nIII from the mixed culture, with the ability to denitrify and metabolize P(HB-co-HV), were used as starter cultures for the elimination of nitrate in ground water. The strains were characterized by diverse techniques. Classical phenotypic studies lead to rRNA group III of the genus Pseudomonas. Results obtained by molecular techniques demonstrated that the 2nIII strains are members of the Comamonadaceae and shows similarities to the genus Acidovorax. However, an integration of the 2nIII isolates within one of the known Acidovorax species is not possible for the moment. The 2nIII starter cultures clustered close to Av. temperans according to their whole cell proteins and fatty acids, whereas in DNA/DNA hybridization no significant DNA binding (< 25%) was found. In contrast a significant but low degree of DNA/DNA hybridization was found between the 2nIII strains and Av. facilis and Av. delafieldii. Our polyphasic results lead to the conclusion that the 2nIII strains may constitute a separate Acicdovorax species.

  17. An inhibitor of the EGF receptor family blocks myeloma cell growth factor activity of HB-EGF and potentiates dexamethasone or anti-IL-6 antibody-induced apoptosis.

    PubMed

    Mahtouk, Karène; Jourdan, Michel; De Vos, John; Hertogh, Catherine; Fiol, Geneviève; Jourdan, Eric; Rossi, Jean-François; Klein, Bernard

    2004-03-01

    We previously found that some myeloma cell lines express the heparin-binding epidermal growth factor-like growth factor (HB-EGF) gene. As the proteoglycan syndecan-1 is an HB-EGF coreceptor as well as a hallmark of plasma cell differentiation and a marker of myeloma cells, we studied the role of HB-EGF on myeloma cell growth. The HB-EGF gene was expressed by bone marrow mononuclear cells in 8 of 8 patients with myeloma, particularly by monocytes and stromal cells, but not by purified primary myeloma cells. Six of 9 myeloma cell lines and 9 of 9 purified primary myeloma cells expressed ErbB1 or ErbB4 genes coding for HB-EGF receptor. In the presence of a low interleukin-6 (IL-6) concentration, HB-EGF stimulated the proliferation of the 6 ErbB1+ or ErbB4+ cell lines, through the phosphatidylinositol 3-kinase/AKT (PI-3K/AKT) pathway. A pan-ErbB inhibitor blocked the myeloma cell growth factor activity and the signaling induced by HB-EGF. This inhibitor induced apoptosis of patients'myeloma cells cultured with their tumor environment. It also increased patients' myeloma cell apoptosis induced by an anti-IL-6 antibody or dexamethasone. The ErbB inhibitor had no effect on the interaction between multiple myeloma cells and stromal cells. It was not toxic for nonmyeloma cells present in patients' bone marrow cultures or for the growth of hematopoietic progenitors. Altogether, these data identify ErbB receptors as putative therapeutic targets in multiple myeloma.

  18. Burden of Diabetes and First Evidence for the Utility of HbA1c for Diagnosis and Detection of Diabetes in Urban Black South Africans: The Durban Diabetes Study

    PubMed Central

    Hird, Thomas R.; Pirie, Fraser J.; Esterhuizen, Tonya M.; O’Leary, Brian; McCarthy, Mark I.; Young, Elizabeth H.; Sandhu, Manjinder S.; Motala, Ayesha A.

    2016-01-01

    Objective Glycated haemoglobin (HbA1c) is recommended as an additional tool to glucose-based measures (fasting plasma glucose [FPG] and 2-hour plasma glucose [2PG] during oral glucose tolerance test [OGTT]) for the diagnosis of diabetes; however, its use in sub-Saharan African populations is not established. We assessed prevalence estimates and the diagnosis and detection of diabetes based on OGTT, FPG, and HbA1c in an urban black South African population. Research Design and Methods We conducted a population-based cross-sectional survey using multistage cluster sampling of adults aged ≥18 years in Durban (eThekwini municipality), KwaZulu-Natal. All participants had a 75-g OGTT and HbA1c measurements. Receiver operating characteristic (ROC) analysis was used to assess the overall diagnostic accuracy of HbA1c, using OGTT as the reference, and to determine optimal HbA1c cut-offs. Results Among 1190 participants (851 women, 92.6% response rate), the age-standardised prevalence of diabetes was 12.9% based on OGTT, 11.9% based on FPG, and 13.1% based on HbA1c. In participants without a previous history of diabetes (n = 1077), using OGTT as the reference, an HbA1c ≥48 mmol/mol (6.5%) detected diabetes with 70.3% sensitivity (95%CI 52.7–87.8) and 98.7% specificity (95%CI 97.9–99.4) (AUC 0.94 [95%CI 0.89–1.00]). Additional analyses suggested the optimal HbA1c cut-off for detection of diabetes in this population was 42 mmol/mol (6.0%) (sensitivity 89.2% [95%CI 78.6–99.8], specificity 92.0% [95%CI: 90.3–93.7]). Conclusions In an urban black South African population, we found a high prevalence of diabetes and provide the first evidence for the utility of HbA1c for the diagnosis and detection of diabetes in black Africans in sub-Saharan Africa. PMID:27560687

  19. Long-term prognostic value of admission haemoglobin A1c (HbA1c) levels in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention

    PubMed Central

    Akgul, Ozgur; Cakmak, Huseyin Altug; Erturk, Mehmet; Surgit, Ozgur; Celik, Omer; Ozturk, Derya; Uzun, Fatih; Akkaya, Emre; Yildirim, Aydın

    2014-01-01

    Introduction Many studies have reported the diagnostic and prognostic value of haemoglobin A1c (HbA1c) levels in patients with acute coronary syndrome. However, the short- and long-term prognostic value of HbA1c level in patients with ST elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) is controversial. Aim To investigate whether admission HbA1c level has a prognostic value for in-hospital, short-, and long-term cardiovascular (CV) mortality and major adverse cardiovascular events in patients with STEMI undergoing primary PCI. Material and methods This prospective study included 443 consecutive patients with STEMI who underwent primary PCI between September 2010 and July 2012. The patients were divided into three groups based on admission HbA1c levels: group I (HbA1c ≤ 5.6%), group II (HbA1c 5.7–6.4%), and group III (HbA1c ≥ 6.5%). The in-hospital, 1-month, and 1-year CV events of all 3 patient groups were followed up. Results A significant association was found between HbA1c level and 1-year primary clinical outcomes, including CV mortality, non-fatal reinfarction, and stroke (p = 0.037). In addition, age, Killip class > 1, and left ventricular ejection fraction were found to be independent predictors of long-term CV mortality in multivariate analysis (hazard ratios (95% confidence interval) 1.081 (1.020–1.146), 4.182 (1.171–14.935), and 0.832 (0.752–0.920); p = 0.009, p = 0.028, and p < 0.001, respectively). Conclusions In this study, we demonstrated that increased admission HbA1c levels were associated with higher rates of major adverse CV events, including mortality, non-fatal reinfarction, and stroke, in patients with STEMI who underwent primary PCI. PMID:25489302

  20. Hb St. Jozef, A Val-->Leu N-terminal mutation leading to retention of the methionine, and partial acetylation found in the globin gene in Cis with a -alpha3.7 thalassemia deletion.

    PubMed

    Harteveld, Cornelis L; Versteegh, Florens G A; van Leer, Eduard H G; Starreveld, Jaap S; Kok, Peter J M J; van Rooijen-Nijdam, Irene; van Delft, Peter; Zanella-Cleon, Isabelle; Becchi, Michel; Wajcman, Henri; Giordano, Piero C

    2007-01-01

    We report a new hemoglobin (Hb) variant found in a 6-year-old girl of Moroccan origin, living in the Dutch city of Gouda. The child was referred because of microcytic and hypochromic parameters. A normal zinc protoporphyirin (ZPP) value excluded iron deficiency and gap-polymerase chain reaction (gap-PCR) revealed a heterozygosity for the common -alpha(3.7) thalassemia deletion, partially justifying the hematological picture. The Hb pattern on alkaline electrophoresis and capillary electrophoresis was normal, while a fraction of 9% preceding the Hb A peak, remained visible on different high performance liquid chromatography (HPLC) devices. This fraction, located in front of the Hb A peak, is usually considered as a Hb A derivate that becomes more expressed in older samples. However, the sample was freshly collected and the peak unusually evident. Therefore, direct sequencing of the alpha-globin genes was performed revealing a GTG-->CTG transversion at codon 1 of the alpha1-globin gene or of the hybrid gene. This point mutation induces a single amino acid substitution from valine to leucine. Electrospray-mass spectrometry (ES-MS) analysis revealed, in addition to this substitution, that the N-terminal methionine was retained and that about 20% of the variant was acetylated. As expected for an association with a -alpha(3.7)-thalassemia (thal) deletion, the non acetylated and acetylated abnormal alpha chain amounted to 32% of the total alpha chains. Family studies revealed that the mutated codon was located in cis of the deletion.

  1. The Individualized Target HbA1c: A New Method for Improving Macrovascular Risk and Glycemia Without Hypoglycemia and Weight Gain.

    PubMed

    Eldor, Roy; Raz, Itamar

    2009-01-01

    Both the DCCT and UKPDS trials demonstrated that improved glycemic control reduces microvascular complications. Inconclusive evidence, however, has remained on the question of the effect of glycemic control on macrovascular disease (with special emphasis on cardiovascular morbidity and mortality). In the last year, the data from four large trials were published, directly addressing this question (ACCORD, ADVANCE, VADT and UKPDS-80), yet the results were conflicting. Close inspection of the structure of three of these trials (ACCORD, ADVANCE and VADT) revealed inadequacies that may explain the unfavorable results, such as the inclusion of mainly elderly patients with previous macrovascular complications. It is not surprising that intensive glycemic control resulted in a rise of hypoglycemic events yet did not decrease macrovascular morbidity or mortality in these cohorts. On the other hand, the UKPDS-80 trial, a follow-up of the original UKPDS, showed that intensive glycemic control was beneficial when initiated in newly diagnosed patients. These results led us to develop a new individualized method of determining the target HbA1c based on the characteristics of the individual. This method considers the patient's possible benefit from glycemic control, the risk of suffering hypoglycemic events and consequences suffered from the hypoglycemic event. It is essential that the target HbA1c be tailored to the patient, with different goals set for the recently diagnosed "healthy" and young patient on the one hand, and the elderly patient with co-morbidities and polypharmacy on the other hand. We further suggest a method of comparing and choosing between the different hypoglycemic drugs available. Drugs should be considered not only based on their hypoglycemic effect but also on several other attributes such as effects on weight, glycemic durability, cardiovascular protection, individual experience with the drug, method of delivery and side effect profiles. Scoring the

  2. Ligand migration and cavities within Scapharca dimeric HbI: Studies by time-resolved crystallography, Xe binding and computational analysis

    PubMed Central

    Knapp, James E.; Pahl, Reinhard; Cohen, Jordi; Nichols, Jeffry C.; Schulten, Klaus; Gibson, Quentin H.; Šrajer, Vukica; Royer, William E.

    2009-01-01

    Summary As in many other hemoglobins, no direct route for migration of ligands between solvent and active site is evident from crystal structures of Scapharca inaequivalvis dimeric HbI. Xenon (Xe) and organic halide binding experiments along with computational analysis presented here reveal protein cavities as potential ligand migration routes. Time-resolved crystallographic experiments show that photodissociated carbon monoxide (CO) docks within 5ns at the distal pocket B-site and at more remote Xe4 and Xe2 cavities. CO rebinding is not affected by the presence of dichloroethane within the major Xe4 protein cavity, demonstrating that this cavity is not on the major exit pathway. The crystal lattice has a substantial influence on ligand migration, suggesting that significant conformational rearrangements may be required for ligand exit. Taken together, these results are consistent with a distal histidine gate as one important ligand entry and exit route, despite its participation in the dimeric interface. PMID:19913484

  3. First report on rapid screening of nanomaterial-based antimicrobial agents against β-lactamase resistance using pGLO plasmid transformed Escherichia coli HB 101 K-12

    NASA Astrophysics Data System (ADS)

    Raj, M. Alpha; Muralidhar, Y.; Sravanthi, M.; Prasad, T. N. V. K. V.; Nissipriya, M.; Reddy, P. Sirisha; Neelima, T. Shoba; Reddy, G. Dilip; Adilaxmamma, K.; Kumar, P. Anand; Krishna, T. Giridhara

    2016-08-01

    Combating antibiotic resistance requires discovery of novel antimicrobials effective against resistant bacteria. Herein, we present for the first time, pGLO plasmid transformed Escherichia coli HB 101 K 12 as novel model for screening of nanomaterial-based antimicrobial agents against β-lactamase resistance. E. coli HB 101 was transformed by pGLO plasmid in the presence of calcium chloride (50 mM; pH 6.1) aided by heat shock (0-42-0 °C). The transformed bacteria were grown on Luria-Bertani agar containing ampicillin (amp) and arabinose (ara). The transformed culture was able to grow in the presence of ampicillin and also exhibited fluorescence under UV light. Both untransformed and transformed bacteria were used for screening citrate-mediated nanosilver (CNS), aloin-mediated nanosilver (ANS), 11-α-keto-boswellic acid (AKBA)-mediated nanosilver (BNS); nanozinc oxide, nanomanganese oxide (NMO) and phytochemicals such as aloin and AKBA. Minimum inhibitory concentrations (MIC) were obtained by microplate method using ρ-iodo nitro tetrazolium indicator. All the compounds were effective against transformed bacteria except NMO and AKBA. Transformed bacteria exhibited reverse cross resistance against aloin. ANS showed the highest antibacterial activity with a MIC of 0.32 ppm followed by BNS (10.32 ppm), CNS (20.64 ppm) and NZO (34.83 ppm). Thus, pGLO plasmid can be used to induce resistance against β-lactam antibiotics and the model can be used for rapid screening of new antibacterial agents effective against resistant bacteria.

  4. A 21 Nucleotide Duplication on the α1- and α2-Globin Genes Involves a Variety of Hypochromic Microcytic Anemias, From Mild to Hb H Disease.

    PubMed

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

    2015-01-01

    α-Thalassemia (α-thal) is a common genetic disorder in Iran and many parts of the world. Genetic defects in the α-globin gene cluster can result in α-thal that may develop into a clinical phenotype varying from almost asymptomatic to a lethal hemolytic anemia. Loss of one functional α gene, indicated as heterozygous α(+)-thal, shows minor hematological abnormalities. Homozygosity for α(+)- or heterozygosity for α(0)-thal have more severe hematological abnormalities due to a markedly reduced α chain output. At the molecular level, the absence of three α-globin genes resulting from the compound heterozygous state for α(0)- and α(+)-thal, lead to Hb H disease. Here we present a 21 nucleotide (nt) duplication consisting of six amino acids and 3 bp of intronic sequence at the exon-intron boundary, in both the α-globin genes, detected by direct DNA sequencing. This duplication was identified in three patients originating from two different Iranian ethnic groups and one Arab during more than 12 years. The clinical presentation of these individuals varies widely from a mild asymptomatic anemia (heterozygote in α1-globin gene) to a severely anemic state, diagnosed as an Hb H individual requiring blood transfusion (duplication on the α2-globin gene in combination with the - -(MED) double α-globin gene deletion). The third individual, who was homozygous for this nt duplication on the α1-globin gene, showed severe hypochromic microcytic anemia and splenomegaly. In the last decade, numerous α-globin mutations have demonstrated the necessity of prenatal diagnosis (PND) for α-thal, and this study has contributed another mutation as important enough that needs to be considered.

  5. UBV stellar photometry of bright stars in GC M5 - I. UV colour-magnitude and colour-colour diagrams and some peculiarities in the HB stellar distribution

    NASA Astrophysics Data System (ADS)

    Markov, H. S.; Spassova, N. M.; Baev, P. V.

    2001-09-01

    We present stellar photometry in the UBV passbands for the globular cluster M5≡NGC 5904. The observations, taken from short-exposure photographic plates and CCD frames, were obtained in the Ritchey-Cretien (RC) focus of the 2-m telescope of the National Astronomy Observatory `Rozhen'. All stars in an annulus with radius 1<=r<=5.5arcmin were measured. We show that the ultraviolet (UV) colour-magnitude diagrams (CMDs) describe different evolutionary stages in a better manner than the `classical' V, B-V diagram. We use HB stars, with known spectroscopic Teff to check the validity of the colour zero-point. A review of all known UV-bright star candidates in M5 is made and some of their parameters are catalogued. Six new stars of this kind are suspected on the basis of their position on the CMD. New assessment of the cluster reddening and metallicity is done using the U-B, B-V diagram. We find that [Fe/H]=-1.38, which confirms the Zinn & West value, contrasting with recent spectroscopic estimates. In an effort to clarify the question of the gap in the blue horizontal branch (BHB) stellar distribution and to investigate some other peculiarities, we use the relatively long-base colour index U-V. A comparison of the observed V, (U-V)0 distribution of horizontal branch (HB) stars with a canonical zero-age horizontal branch (ZAHB) model reveals that the hottest stars rise above the model line. This is similar to the `u-jump' found in the Strömgren photometry. 18 BHB stars with (B-V)0∈[-0.02/0.18] are used to estimate their ultraviolet deficiency. It is shown that low-gravity (logg<=2) Kurucz's atmospheric models fit the observed distribution of these stars along the two-colour diagram well.

  6. Effects of in vivo exposure to UV filters (4-MBC, OMC, BP-3, 4-HB, OC, OD-PABA) on endocrine signaling genes in the insect Chironomus riparius.

    PubMed

    Ozáez, Irene; Martínez-Guitarte, José Luis; Morcillo, Gloria

    2013-07-01

    There is increasing evidence indicating that several UV filters might have endocrine disruptive effects. Numerous studies have evaluated hormonal effects in vertebrates, mainly reporting estrogenic and androgenic activities in mammals and fishes. There is only limited knowledge about potential endocrine activity in invertebrate hormonal systems. In this work, the effects on endocrine signaling genes of six frequently used UV filters were investigated in Chironomus riparius, a reference organism in aquatic toxicology. The UV filters studied were: octyl-p-methoxycinnamate (OMC) also called 2-ethylhexyl-4-methoxycinnamate (EHMC); 4-methylbenzylidene camphor (4-MBC); benzophenone-3 (BP-3); 4-hidroxybenzophenone (4-HB); octocrylene (OC); and octyldimethyl-p-aminobenzoate (OD-PABA). After in vivo exposure at different dosages, expression levels of the genes coding for the ecdysone receptor (EcR), the ultraspiracle (usp, ortholog of the RXR) and the estrogen-related receptor (ERR) were quantified by Real Time PCR. The EcR gene was significantly upregulated by 4-MBC, OMC/EHMC and OD-PABA, with a dose-related response following 24h exposure. In contrast, the benzophenones, BP-3 and 4-HB, as well as OC did not alter this gene at the same exposure conditions. The transcription profiles of the usp and ERR genes were not significantly affected, except for BP-3 that inhibited the usp gene at the highest concentration. To our knowledge, this is the first experimental evidence in invertebrates of a direct effect of UV filters on endocrine-related genes, and is consistent with the known effects on vertebrate hormonal receptor genes. The capability of 4-MBC, OMC/EHMC and OD-PABA to stimulate the expression of the ecdysone receptor, a key transcription factor for the ecdysone-genomic response in arthropods, suggests the possibility of a broad and long-term effect on this hormonal pathway. These findings strengthen the need for further research about the ecotoxicological implications

  7. Mobilization of the genetically engineered plasmid pHSV106 from Escherichia coli HB101(pHSV106) to Enterobacter cloacae in drinking water.

    PubMed

    Sandt, C H; Herson, D S

    1991-01-01

    We have used triparental matings to demonstrate transfer (mobilization) of the nonconjugative genetically engineered plasmid pHSV106, which contains the thymidine kinase gene of herpes simplex virus cloned into pBR322, from Escherichia coli HB101 to an environmental isolate of Enterobacter cloacae in sterile drinking water. This is the first demonstration of a two-step mobilization of a genetically engineered plasmid in any type of fresh water, including drinking water. Transfer was mediated by R plasmid R100-1 of E. coli ED2149(R100-1). Matings in drinking water at 15, 25, and 35 degrees C yielded recombinants, the number of which increased with increasing temperature. Numbers of recombinants obtained were 2 orders of magnitude lower than those obtained from matings in Trypticase soy broth. High concentrations of parental organisms (2.6 x 10(8) to 2.0 x 10(9) CFU/ml) were required. During 1 week of incubation in drinking water, number of parental organisms and recombinants resulting from mobilization remained constant in the absence of indigenous organisms and declined in their presence. Using oligonucleotide probes for the cloned foreign DNA (thymidine kinase gene) and plasmid vector DNA (ampicillin resistance gene), we demonstrated that both genes were transferred to E. cloacae in the mobilization process. In one recombinant selected for detailed study, the plasmids containing these genes differed in size from all forms of pHSV106 present in E. coli HB101(pHSV106), indicating that DNA rearrangement had occurred. This recombinant maintained its plasmids in unchanged form for 15 days in drinking water. A second rearrangement occurred during serial passage of this recombinant on selective media.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. The Effects of a Mindfulness-Based Intervention on Emotional Distress, Quality of Life, and HbA1c in Outpatients With Diabetes (DiaMind)

    PubMed Central

    van Son, Jenny; Nyklíček, Ivan; Pop, Victor J.; Blonk, Marion C.; Erdtsieck, Ronald J.; Spooren, Pieter F.; Toorians, Arno W.; Pouwer, François

    2013-01-01

    OBJECTIVE Emotional distress is common in outpatients with diabetes, affecting ∼20–40% of the patients. The aim of this study was to determine the effectiveness of group therapy with Mindfulness-Based Cognitive Therapy (MBCT), relative to usual care, for patients with diabetes with regard to reducing emotional distress and improving health-related quality of life and glycemic control. RESEARCH DESIGN AND METHODS In the present randomized controlled trial, 139 outpatients with diabetes (type 1 or type 2) and low levels of emotional well-being were randomized to MBCT (n = 70) or a waiting list group (n = 69). Primary outcomes were perceived stress (Perceived Stress Scale), anxiety and depressive symptoms (Hospital Anxiety and Depression Scale), mood (Profiles of Mood States), and diabetes-specific distress (Problem Areas In Diabetes). Secondary outcomes were health-related quality of life (12-Item Short-Form Health Survey), and glycemic control (HbA1c). Assessments were conducted at baseline and at 4 and 8 weeks of follow-up. RESULTS Compared with control, MBCT was more effective in reducing stress (P < 0.001, Cohen d = 0.70), depressive symptoms (P = 0.006, d = 0.59), and anxiety (P = 0.019, d = 0.44). In addition, MBCT was more effective in improving quality of life (mental: P = 0.003, d = 0.55; physical: P = 0.032, d = 0.40). We found no significant effect on HbA1c or diabetes-specific distress, although patients with elevated diabetes distress in the MBCT group tended to show a decrease in diabetes distress (P = 0.07, d = 0.70) compared with the control group. CONCLUSIONS Compared with usual care, MBCT resulted in a reduction of emotional distress and an increase in health-related quality of life in diabetic patients who had lower levels of emotional well-being. PMID:23193218

  9. Can Trimodal Distribution of HbS Levels in Sickle Cell Traits Be Used To Predict the Associated Alpha-Thalassemia For Screening Cases in Central India?

    PubMed Central

    WARPE, BM; SHRIKHANDE, AV; POFLEE, SV

    2016-01-01

    Background: Until now, trimodal distribution of HbS has been seen by six different studies in the world when associated with alpha-thalassemia with confirmation by corresponding alpha-genotyping studies. The RBC indices reduce as alpha-globin genes reduce in sickle cell trait (SCT) patients, which decreases the extent of intra-vascular sickling and thus betters the clinical course of the patients. This is a pioneer study conducted on Central Indian poor population to use the already proven six studies to screen associated alpha-thalassemia in SCT patients thus, circumventing the much costlier alpha-genotyping studies. Moreover, it aimed to study the haematological parameters in such cases. Methods: The study was performed at RHDMC, IGGMC, Nagpur, India from 2003 to 2012. The sample population was suspected cases of haemolytic anaemia. CBC and RBC indices were obtained by a cell analyzer. The sickle solubility test positively screened cases were confirmed by agar-gel haemoglobin electrophoresis at pH 8.6. Finally, quantitative assessment of haemoglobin variants was performed by HPLC. Results: Out of total 5819 cases over ten years, 933 cases were sickle heterozygotes. Overall, 180/933 subjects were predicted to be homozygous alpha-thalassemia and 338/933 were heterozygous alpha-thalassemia, based on trimodal distribution of HbS. Conclusion: Genotyping is costlier for majority of the poor non-affording patients in Indian government set-ups, so this study is suitable to screen for associated alpha-thalassemia in SCT patients. PMID:27499774

  10. Severe α-Thalassemia Intermedia Due to a Compound Heterozygosity for the Highly Unstable Hb Adana (HBA2: c.179G>A) and a Novel Codon 24 (HBA2: c.75T>A) Mutation

    PubMed Central

    Megawati, Dewi; Nainggolan, Ita M.; Swastika, Maria; Susanah, Susi; Mose, Johanes C.; Harahap, Alida R.

    2014-01-01

    HBA2 We report a novel mutation at codon 24 of the α2-globin gene (HBA2: c.75T > A) found in a Sundanese family. This novel mutation was detected during prenatal diagnosis. The couple already had a 7-year-old boy who exhibited clinically severe α-thalassemia intermedia (α-TI), and he was found to be a compound heterozygote for the novel mutation at codon 24 and the previously described Hb Adana (HBA2: c.179G > A) at codon 59 of the α2-globin gene. The father was a carrier of the novel point mutation and showed normal hemoglobin (Hb) and a low mean corpuscular volume (MCV) and mean corpuscular Hb (MCH) value. PMID:24351118

  11. Severe α-thalassemia intermedia due to a compound heterozygosity for the highly unstable Hb Adana (HBA2: c.179G>A) and a novel codon 24 (HBA2: c.75T>A) mutation.

    PubMed

    Megawati, Dewi; Nainggolan, Ita M; Swastika, Maria; Susanah, Susi; Mose, Johanes C; Harahap, Alida R; Setianingsih, Iswari

    2014-01-01

    We report a novel mutation at codon 24 of the α2-globin gene (HBA2: c.75T > A) found in a Sundanese family. This novel mutation was detected during prenatal diagnosis. The couple already had a 7-year-old boy who exhibited clinically severe α-thalassemia intermedia (α-TI), and he was found to be a compound heterozygote for the novel mutation at codon 24 and the previously described Hb Adana (HBA2: c.179G > A) at codon 59 of the α2-globin gene. The father was a carrier of the novel point mutation and showed normal hemoglobin (Hb) and a low mean corpuscular volume (MCV) and mean corpuscular Hb (MCH) value.

  12. Determination of the value of glycated hemoglobin HbA1c and fructosamine in assessing the risk of perioperative complications after cardiac surgery in patients with type 2 diabetes

    PubMed Central

    Wróbel, Marta; Rokicka, Dominika; Szymborska-Kajanek, Aleksandra; Foremny, Jerzy; Nadziakiewicz, Paweł; Zembala, Marian; Strojek, Krzysztof

    2016-01-01

    Introduction Patients with diabetes have a worse postoperative course and longer length of hospital stay after surgery. A good indicator of proper long-term (3 months) glycemic control is glycated hemoglobin (HbA1c), and fructosamine in the short term (2–3 weeks). Aim To determine the degree of glycemic control evaluated preoperatively by HbA1c and/or fructosamine influence on the postoperative course of patients with diabetes undergoing coronary artery bypass grafting (CABG) in 2014–2015. Material and methods Before the operation HbA1c (N < 7.0) and fructosamine (N < 280 µmol/l) were measured and depending on the results the respondents were divided into 4 groups: group I (n = 46) – normal both parameters; group II (n = 22) – high both values; group III (n = 4) – normal fructosamine/HbA1c high; group IV (n = 33) – high HbA1c/fructosamine normal. Statistical analysis was performed using the t-test assuming p < 0.05 to be statistically significant. Results One hundred and five patients were treated by CABG/OPCAB (39 female, 66 males). The mean age was 65.7 ±7.3, HbA1c: 7.23 ±1.2%, fructosamine: 261.8 ±43.8. There was no difference in the incidence of other postoperative complications between the two groups. Conclusions Glycated hemoglobin and fructosamine levels to a similar extent define the risk of perioperative complications in patients undergoing cardiac surgery. In patients in whom there is a need to quickly compensate for elevated blood glucose consider enabling determination of fructosamine. PMID:28096825

  13. Effect of the IncP-1β plasmid pHB44 on the population dynamics of Burkholderia terrae BS001 in the Lyophyllum sp. strain Karsten mycosphere under different iron conditions.

    PubMed

    Zhang, Miaozhi; Yang, Pu; van Elsas, Jan Dirk

    2016-02-01

    Burkholderia terrae strain BS001 is a well-described inhabitant of the mycosphere of diverse fungi. In the interaction between this bacterium and its fungal host in soil, competition for iron might be a key process. Here, we address the capacity of the broad-host-range IncP-1β plasmid pHB44, originally isolated in Variovorax paradoxus HB44, to enhance or modulate the competitiveness of B. terrae BS001 under different soil iron levels when confronted with (young versus ageing) mycelia of Lyophyllum sp. strain Karsten in microcosms. The data revealed that, in most cases, plasmid pHB44 reduced the fitness of its host in the mycosphere, possibly due to a metabolic burden effect. However, an opposite effect was found under low-iron conditions at the extreme tips of the soil-exploring Lyophyllum sp. strain Karsten mycelium. The negative effect of plasmid pHB44 on strain BS001 population sizes was clearly offset by fitness enhancement under these conditions. Moreover, as evidenced by using plasmid pSUP104 as a tracer, plasmid pHB44 was transferred from the B. terrae BS001 host into V. paradoxus BS64 in the ageing mycosphere, but not in bulk soil. Strikingly, successful plasmid establishment in the new host was more prominent in the iron-limited than in the 'high-iron' mycosphere habitat, indicating plasmid pHB44 was required in the V. paradoxus host as a fitness stimulator in the iron-limited condition. Taken together, the data suggest that efficiency of iron acquisition only served as the selective mechanism under certain conditions of iron availability in the soil, specifically promoting the fitness of V. paradoxus transconjugants. Not only is the mycosphere to be regarded as a selective arena in which horizontal gene transfer across the bacterial inhabitants is spurred, but the outcome of the adaptive processes is strongly shaped by competitive events among the local organisms.

  14. Ferromagnetic coupling between low- and high-spin iron(III) ions in the tetranuclear complex fac-[[FeIII[HB(pz)3](CN)2(mu-CN)]3FeIII(H2O)3]* 6H2O ([HB(pz)3]- = hydrotris(1-pyrazolyl)borate).

    PubMed

    Lescouëzec, Rodrigue; Vaissermann, Jacqueline; Lloret, Francesc; Julve, Miguel; Verdaguer, Michel

    2002-11-18

    The novel mononuclear PPh4-fac-[FeIII[HB(pz)3](CN)3]*H2O (1) [PPh4+= tetraphenylphosphonium cation; (HB(pz)3)- = hydrotris(1-pyrazolyl)borate] and tetranuclear fac-[[FeIII[HB(pz)3](CN)2(mu-CN)]3FeIII(H2O)3]*6H2O (2) have been prepared and characterized by X-ray diffraction analysis. Crystal data for compound 1: monoclinic, space group P21/c, a = 9.575(3) A, b = 21.984(4) A, c = 16.863(3) A, beta = 100.34(2) degrees, U = 3486(1) A3, Z = 4. Crystal data for compound 2: orthorhombic, space group Pnam, a = 14.084(3) A, b = 14.799(4) A, c = 25.725(5) A, U = 5362(2) A3, Z = 4. Compound 1 is a low-spin iron(III) compound with three cyanide ligands in fac arrangement and a tridentate pyrazolylborate ligand building a distorted octahedral environment around the iron atom. Compound 2 is the first example of a molecular species containing three peripheral low-spin iron(III) ions linked to a central high-spin iron(III) cation by single cyanide bridges, the anion of 1 acting as a monodentate ligand in 2. Variable-temperature magnetic susceptibility measurements of 2 reveal the occurrence of a significant ferromagnetic coupling between the three peripheral low-spin iron(III) centers and the central high-spin iron(III) ion cations leading to a low-lying nonet spin state.

  15. The Complete Sequences and Ecological Roles of Two IncP-1β Plasmids, pHB44 and pBS64, Isolated from the Mycosphere of Laccaria proxima

    PubMed Central

    Zhang, Miaozhi; Brons, Jolanda K.; van Elsas, Jan Dirk

    2016-01-01

    Two novel plasmids, coined pHB44 and pBS64, were recently found in Variovorax paradoxus strains HB44 and BS64 isolated from the mycosphere of Laccaria proxima, on two different sampling occasions. We here describe the full sequences of pHB44 and pBS64 and establish their evolutionary placement and ecological function. Both plasmids, unique for mycospheric V. paradoxus, were around 58 kb in size. They possessed, in a very similar fashion, three main plasmid backbone regions, which were predicted to be involved in plasmid replication, central control of maintenance, and conjugational transfer. Phylogenetic inference on the basis of seven selected and concatenated plasmid backbone genes provided solid evidence for the placement of the two plasmids in the IncP-1β1 group, with the recently isolated IncP-1β1 plasmid pMBUI8 as the closest relative. A comparative analysis of the sequences present in each of the recombinational hot spots (RHS) I to III across plasmids pHB44, pBS64, and pMBUI8 revealed the insertions found in plasmids pHB44 and pBS64 to be different from those of pMBUI8. Whereas, in the former two plasmids, RHS I and III were devoid of any major inserts, their RHS II regions contained inserts of 15,043 (pHB44) and 16,406 kb (pBS64), against about 9,3 kb for pMBUI8. Interestingly, these regions were highly similar across plasmids pHB44 and pBS64, and differed from that of pMBUI8. Closer inspection revealed the insert in the former plasmids to contain, next to transposases, an “mmf” gene cassette previously reported to encode metal “responsiveness” in the PromA plasmid pMOL98. Whereas the plasmid pHB44 RHS II contained the canonical mmf sequence, that in pBS64 contained, in addition, a “two-gene duplicated region” flanking the mmf C2 gene. In vitro experiments on the growth and survival of strains with or without plasmid pHB44 suggested this plasmid was involved in the binding and import of Fe3+ as well as V3+ ions into the host cells, thus

  16. Simultaneous detection of Hb constant spring (α142, TAA>CAA, α2) and the α2 IVS-I donor site (-TGAGG) deletion by a simple polymerase chain reaction-based method in Iran.

    PubMed

    Akhavan-Niaki, Haleh; Banihashemi, Ali; Mostafazadeh, Amrollah; Kholghi Oskooei, Vahid; Azizi, Mandana; Youssefi Kamangar, Reza; Elmi, Maryam Mitra

    2012-01-01

    Hb Constant Spring (Hb CS, codon 142, TAA>CAA, α2) (HBA2:c.427T>C) and α2 IVS-I donor site (GAGGTGAGG>GAGG - - - - -) (HBA2:c.95+2_95+6delTGAGG) are nondeletional α-thalassemia (α-thal) mutations found all over the world. Identification of α-thal genotypes in at-risk couples for severe anemia or in highly heterogeneous populations requires rapid, accurate and cost-effective genotyping methods. In this study, a pair of primers were used to specifically amplify an 883 bp fragment from the α2-globin gene in order to simultaneously identify these two mutations by a PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) method. We determined the genotypic frequencies of Hb CS and the α2 IVS-I donor site mutations after amplification and enzymatic digestion with Tru9I in 238 northern Iranian samples referred for α-thal testing. Hb CS and the α2 IVS-I donor site mutations accounted for 21 (8.8%) and 29 (12.2%) of the nondeletional cases. This genotyping assay has proven to be a rapid, reliable and useful diagnostic tool for simultaneous detection of these two anomalies for genetic counseling or further prenatal diagnosis.

  17. A new hemoglobin variant: Hb Meylan [β73(E17)Asp → Phe; HBB: c.220G>T; c.221A>T] with a double base mutation at the same codon.

    PubMed

    Renoux, Céline; Feray, Cécile; Joly, Philippe; Zanella-Cleon, Isabelle; Garcia, Caroline; Lacan, Philippe; Couprie, Nicole; Francina, Alain

    2015-01-01

    We report a new β-globin chain variant: Hb Meylan [β73(E17)Asp → Phe; HBB: c.220G>T; c.221A>T]. The new variant results from a double nucleotide mutation at the same codon. The possible molecular mechanisms are discussed.

  18. Giant extracellular Glossoscolex paulistus Hemoglobin (HbGp) upon interaction with cethyltrimethylammonium chloride (CTAC) and sodium dodecyl sulphate (SDS) surfactants: Dissociation of oligomeric structure and autoxidation.

    PubMed

    Santiago, Patricia S; Moreira, Leonardo M; de Almeida, Erika V; Tabak, Marcel

    2007-04-01

    The effects of two ionic surfactants on the oligomeric structure of the giant extracellular hemoglobin of Glossoscolex paulistus (HbGp) in the oxy - form have been studied through the use of several spectroscopic techniques such as electronic optical absorption, fluorescence emission, light scattering, and circular dichroism. The use of anionic sodium dodecyl sulphate (SDS) and cationic cethyltrimethyl ammonium chloride (CTAC) has allowed to differentiate the effects of opposite headgroup charges on the oligomeric structure dissociation and hemoglobin autoxidation. At pH 7.0, both surfactants induce the protein dissociation and a significant oxidation. Spectral changes occur at very low CTAC concentrations suggesting a significant electrostatic contribution to the protein-surfactant interaction. At low protein concentration, 0.08 mg/ml, some light scattering within a narrow CTAC concentration range occurs due to protein-surfactant precipitation. Light scattering experiments showed the dissociation of the oligomeric structure by SDS and CTAC, and the effect of precipitation induced by CTAC. At higher protein concentrations, 3.0 mg/ml, a precipitation was observed due to the intense charge neutralization upon formation of ion pair in the protein-surfactant precipitate. The spectral changes are spread over a much wider SDS concentration range, implying a smaller electrostatic contribution to the protein-surfactant interactions. The observed effects are consistent with the acid isoelectric point (pI) of this class of hemoglobins, which favors the intense interaction of HbGp with the cationic surfactant due to the existence of excess acid anionic residues at the protein surface. Protein secondary structure changes are significant for CTAC at low concentrations while they occur at significantly higher concentrations for SDS. In summary, the cationic surfactant seems to interact more strongly with the protein producing more dramatic spectral changes as compared to the

  19. Dietary glycemic index and glycemic load in relation to HbA1c in Japanese obese adults: a cross-sectional analysis of the Saku Control Obesity Program

    PubMed Central

    2012-01-01

    Background Dietary glycemic index or load is thought to play an important role in glucose metabolism. However, few studies have investigated the relation between glycemic index (GI) or load (GL) and glycemia in Asian populations. In this cross-sectional analysis of a randomized controlled trial, the Saku Control Obesity Program, we examined the relation between the baseline GI or GL and glycemia (HbA1c and fasting plasma glucose [FPG] levels), insulin resistance (HOMA-IR), β-cell function (HOMA-β), and other metabolic risk factors (lipid levels, diastolic and systolic blood pressure, and adiposity measures). Methods The participants were 227 obese Japanese women and men. We used multiple linear regression models and logistic regression models to adjust for potential confounding factors such as age, sex, visceral fat area, total energy intake, and physical activity levels. Results After adjustments for potential confounding factors, GI was not associated with HbA1c, but GL was positively associated with HbA1c. For increasing quartiles of GI, the adjusted mean HbA1c were 6.3%, 6.7%, 6.4%, and 6.4% (P for trend = 0.991). For increasing quartiles of GL, the adjusted mean HbA1c were 6.2%, 6.2%, 6.6%, and 6.5% (P for trend = 0.044). In addition, among participants with HbA1c ≥ 7.0%, 20 out of 28 (71%) had a high GL (≥ median); the adjusted odds ratio for HbA1c ≥ 7.0% among participants with higher GL was 3.1 (95% confidence interval [CI] = 1.2 to 8.1) compared to the participants with a lower GL (

  20. Gene-Silencing-Induced Changes in Carbohydrate Conformation in Relation to Bioenergy Value and Carbohydrate Subfractions in Modeled Plant (Medicago sativa) with Down-Regulation of HB12 and TT8 Transcription Factors

    PubMed Central

    Li, Xinxin; Hannoufa, Abdelali; Zhang, Yonggen; Yu, Peiqiang

    2016-01-01

    Gene silencing with RNA interference (RNAi) technology may be capable of modifying internal structure at a molecular level. This structural modification could affect biofunctions in terms of biodegradation, biochemical metabolism, and bioactive compound availability. The objectives of this study were to (1) Detect gene silencing-induced changes in carbohydrate molecular structure in an alfalfa forage (Medicago sativa spp. sativa: alfalfa) with down-regulation of genes that encode transcription factors TT8 and HB12; (2) Determine gene silencing-induced changes in nutrient bioutilization and bioavailability in the alfalfa forage (Medicago sativa); and (3) Quantify the correlation between gene silencing-induced molecular structure changes and the nutrient bioutilization and bioavailability in animals of ruminants. The experimental treatments included: T1 = Non-transgenic and no-gene silenced alfalfa forage (code “NT”); T2 = HB12-RNAi forage with HB12 gene down regulation (code “HB12”); T3 = TT8-RNAi forage with TT8 gene down regulation (code “TT8”). The HB12 and TT8 gene silencing-induced molecular structure changes were determined by non-invasive and non-destructive advanced molecular spectroscopy in a middle infrared radiation region that focused on structural, non-structural and total carbohydrate compounds. The nutrient bioutilization and bioavailability of the modified forage were determined using NRC-2001 system in terms of total digestive nutrient (TDN), truly digestible fiber (tdNDF), non-fiber carbohydrate (tdNDF), fatty acid (tdFA), crude protein (tdCP) and bioenergy profiles (digestible energy, metabolizable energy, net energy) for ruminants. The carbohydrate subfractions were evaluated using the updated CNCPS 6.0 system. The results showed that gene silencing significantly affected tdNFC (42.3 (NT) vs. 38.7 (HB12) vs. 37.4% Dry Matter (TT8); p = 0.016) and tdCP (20.8 (NT) vs. 19.4 (HB12) vs. 22.3% DM (TT8); p = 0.009). The gene-silencing also

  1. Gene-Silencing-Induced Changes in Carbohydrate Conformation in Relation to Bioenergy Value and Carbohydrate Subfractions in Modeled Plant (Medicago sativa) with Down-Regulation of HB12 and TT8 Transcription Factors.

    PubMed

    Li, Xinxin; Hannoufa, Abdelali; Zhang, Yonggen; Yu, Peiqiang

    2016-05-13

    Gene silencing with RNA interference (RNAi) technology may be capable of modifying internal structure at a molecular level. This structural modification could affect biofunctions in terms of biodegradation, biochemical metabolism, and bioactive compound availability. The objectives of this study were to (1) Detect gene silencing-induced changes in carbohydrate molecular structure in an alfalfa forage (Medicago sativa spp. sativa: alfalfa) with down-regulation of genes that encode transcription factors TT8 and HB12; (2) Determine gene silencing-induced changes in nutrient bioutilization and bioavailability in the alfalfa forage (Medicago sativa); and (3) Quantify the correlation between gene silencing-induced molecular structure changes and the nutrient bioutilization and bioavailability in animals of ruminants. The experimental treatments included: T1 = Non-transgenic and no-gene silenced alfalfa forage (code "NT"); T2 = HB12-RNAi forage with HB12 gene down regulation (code "HB12"); T3 = TT8-RNAi forage with TT8 gene down regulation (code "TT8"). The HB12 and TT8 gene silencing-induced molecular structure changes were determined by non-invasive and non-destructive advanced molecular spectroscopy in a middle infrared radiation region that focused on structural, non-structural and total carbohydrate compounds. The nutrient bioutilization and bioavailability of the modified forage were determined using NRC-2001 system in terms of total digestive nutrient (TDN), truly digestible fiber (tdNDF), non-fiber carbohydrate (tdNDF), fatty acid (tdFA), crude protein (tdCP) and bioenergy profiles (digestible energy, metabolizable energy, net energy) for ruminants. The carbohydrate subfractions were evaluated using the updated CNCPS 6.0 system. The results showed that gene silencing significantly affected tdNFC (42.3 (NT) vs. 38.7 (HB12) vs. 37.4% Dry Matter (TT8); p = 0.016) and tdCP (20.8 (NT) vs. 19.4 (HB12) vs. 22.3% DM (TT8); p = 0.009). The gene-silencing also affected

  2. Multi-ethnic differences in HbA1c, blood pressure, and low-density-lipid cholesterol control among South Africans living with type 2 diabetes, after a 4-year follow-up

    PubMed Central

    Pinchevsky, Yacob; Shukla, Varada J; Butkow, Neil; Chirwa, Tobias; Raal, Frederick

    2016-01-01

    Purpose Our study set out to examine if disparities in control of glycated hemoglobin (HbA1c), blood pressure (BP), and low-density-lipoprotein cholesterol (LDL-C) existed among an urban multi-ethnic cohort of South Africans, living with type 2 diabetes mellitus (T2DM). Patients and methods This longitudinal, retrospective study consisted of 261 men and women with previously diagnosed T2DM who attended Charlotte Maxeke Johannesburg Academic Hospital, South Africa across two time periods 2009 and 2013. Demographic and clinical data were extracted from consecutive medical records. The primary outcome was to determine achievements in HbA1c, BP, and LDL-C among ethnic groups using evidence-based goals. Results The mean age of the cohort was 64 (±10.6) years, females represented 55%, and the self-reported diabetes duration was 16 (±10.6) years as at 2013. Black Africans (42.9%, n=112 of 261) were more likely to reach the HbA1c target (<7%) and less likely to have had retinopathy, nephropathy, or cardiovascular disease. Over two-thirds of mixed-ancestry patients attained the BP target (<140/80 mmHg), while 90.2% of Caucasians achieved LDL-C goals (<2.5 mmol/L). Overall, across the ethnic groups studied, we found that HbA1c control deteriorated over time, although BP levels remained the same and LDL-C levels drastically improved. Conclusion There was poor control of HbA1c, BP, and LDL-C across all ethnic groups. Although a minority achieved recommended targets, some ethnic groups appeared to have worse control than others. Timely aggressive actions in particularly high-risk ethnic groups will prevent/delay the complications commonly associated with T2DM. PMID:27895508

  3. Effect of baseline HbA1c level on the development of diabetes by lifestyle intervention in primary healthcare settings: insights from subanalysis of the Japan Diabetes Prevention Program

    PubMed Central

    Sakane, Naoki; Sato, Juichi; Tsushita, Kazuyo; Tsujii, Satoru; Kotani, Kazuhiko; Tominaga, Makoto; Kawazu, Shoji; Sato, Yuzo; Usui, Takeshi; Kamae, Isao; Yoshida, Toshihide; Kiyohara, Yutaka; Sato, Shigeaki; Tsuzaki, Kokoro; Takahashi, Kaoru; Kuzuya, Hideshi

    2014-01-01

    Objectives To determine the effects of a lifestyle intervention on the development of type 2 diabetes mellitus (T2DM) among participants with impaired glucose tolerance (IGT), in particular in the subgroup with baseline glycated hemoglobin (HbA1c) levels ≥5.7%, in primary healthcare settings. Design Randomized controlled trial. Setting 32 healthcare centers in Japan. Participants Participants with IGT, aged 30–60 years, were randomly assigned to either an intensive lifestyle intervention group (ILG) or a usual care group (UCG). Interventions During the initial 6 months, participants in the ILG received four group sessions on healthy lifestyles by public health providers. An individual session was further conducted biannually during the 3 years. Participants in the UCG received usual care such as one group session on healthy lifestyles. Outcome measures The primary endpoint was the development of T2DM based on an oral glucose tolerance test. Results The mean follow-up period was 2.3 years. The annual incidence of T2DM were 2.7 and 5.1/100 person-years of follow-up in the ILG (n=145) and UCG (n=149), respectively. The cumulative incidence of T2DM was significantly lower in the ILG than in the UCG among participants with HbA1c levels ≥5.7% (log-rank=3.52, p=0.06; Breslow=4.05, p=0.04; Tarone-Ware=3.79, p=0.05), while this was not found among participants with HbA1c levels <5.7%. Conclusions Intensive lifestyle intervention in primary healthcare setting is effective in preventing the development of T2DM in IGT participants with HbA1c levels ≥5.7%, relative to those with HbA1c levels <5.7%. Trial registration number UMIN000003136. PMID:25452854

  4. Simeprevir and Sofosbuvir Combination Treatment in a Patient with HCV Cirrhosis and HbS Beta 0-Thalassemia: Efficacy and Safety despite Baseline Hyperbilirubinemia

    PubMed Central

    Deutsch, Melanie; Georgalas, Athanasios; Poulakidas, Helias; Karnesis, Lazaros

    2016-01-01

    Hyperbilirubinemia is an adverse reaction of simeprevir (SMV). The majority of these patients were taking concurrent ribavirin presenting elevated unconjugated hyperbilirubinemia due to hemolysis. However, cases of hepatic failure with elevated bilirubin level have also been reported in patients with decompensated cirrhosis. We describe a 51-year-old female patient with HbS beta 0-thalassemia and recently diagnosed compensated cirrhosis due to chronic hepatitis C infection. Laboratory evaluation revealed total bilirubin: 2.7 mg/dL and serum HCV-RNA 137.204 IU/mL. HCV was genotyped as 4. A FibroScan revealed 35.3 kPa. She was considered as illegible for pegylated-interferon-free treatment with direct acting antivirals and a course with simeprevir and sofosbuvir (SOF) combination for twelve weeks was planned. Hyperbilirubinemia developed from the beginning with peak values during the 3rd month of treatment. However, no findings of liver decompensation were noticed. Hyperbilirubinemia was benign and fully reversible and our patient finally achieved sustained virological response 24 weeks after the end of treatment. PMID:27042368

  5. Simeprevir and Sofosbuvir Combination Treatment in a Patient with HCV Cirrhosis and HbS Beta 0-Thalassemia: Efficacy and Safety despite Baseline Hyperbilirubinemia.

    PubMed

    Papadopoulos, Nikolaos; Deutsch, Melanie; Georgalas, Athanasios; Poulakidas, Helias; Karnesis, Lazaros

    2016-01-01

    Hyperbilirubinemia is an adverse reaction of simeprevir (SMV). The majority of these patients were taking concurrent ribavirin presenting elevated unconjugated hyperbilirubinemia due to hemolysis. However, cases of hepatic failure with elevated bilirubin level have also been reported in patients with decompensated cirrhosis. We describe a 51-year-old female patient with HbS beta 0-thalassemia and recently diagnosed compensated cirrhosis due to chronic hepatitis C infection. Laboratory evaluation revealed total bilirubin: 2.7 mg/dL and serum HCV-RNA 137.204 IU/mL. HCV was genotyped as 4. A FibroScan revealed 35.3 kPa. She was considered as illegible for pegylated-interferon-free treatment with direct acting antivirals and a course with simeprevir and sofosbuvir (SOF) combination for twelve weeks was planned. Hyperbilirubinemia developed from the beginning with peak values during the 3rd month of treatment. However, no findings of liver decompensation were noticed. Hyperbilirubinemia was benign and fully reversible and our patient finally achieved sustained virological response 24 weeks after the end of treatment.

  6. Lipases and esterases from extremophiles: overview and case example of the production and purification of an esterase from Thermus thermophilus HB27.

    PubMed

    Fuciños, Pablo; González, Roberto; Atanes, Estrella; Sestelo, Ana Belén Fernández; Pérez-Guerra, Nelson; Pastrana, Lorenzo; Rúa, María Luisa

    2012-01-01

    Extremophiles are organisms that have evolved to exist in a variety of extreme environments. They fall into a number of different classes that include thermophiles, halophiles, acidophiles, alkalophiles, psychrophiles, and barophiles (piezophiles). Extremophiles have the potential to produce uniquely valuable biocatalysts that function under conditions in which usually the enzymes of their nonextremophilic counterparts could not. Among novel enzymes isolated from extremophilic microorganisms, hydrolases, and particularly lipases and esterases are experiencing a growing demand. Lipases (EC 3.1.1.3) and esterases (EC 3.1.1.1) catalyze the cleavage of ester bounds in aqueous media and the reverse reaction in organic solvents. Both lipolytic enzymes have relevant applications in food, dairy, detergent, biofuel, and pharmaceutical industries. Here, we summarize the properties of lipases and esterases from the main extremophile groups: thermophiles and hyperthermophiles, psychrophiles, halophiles, alkalophiles/acidophiles, and solvent-resistant microorganisms.We report the biomass and lipolytic activity production by Thermus thermophilus HB27 in 5-L stirred-tank bioreactor at 70°C. Suitability of thermal spring water for culture media formulation is shown. In addition, a protocol to isolate and purify a cell-bound esterase from this microorganism is described.

  7. Optimal Conditions for Continuous Immobilization of Pseudozyma hubeiensis (Strain HB85A) Lipase by Adsorption in a Packed-Bed Reactor by Response Surface Methodology

    PubMed Central

    Bussamara, Roberta; Dall'Agnol, Luciane; Schrank, Augusto; Fernandes, Kátia Flávia; Vainstein, Marilene Henning

    2012-01-01

    This study aimed to develop an optimal continuous process for lipase immobilization in a bed reactor in order to investigate the possibility of large-scale production. An extracellular lipase of Pseudozyma hubeiensis (strain HB85A) was immobilized by adsorption onto a polystyrene-divinylbenzene support. Furthermore, response surface methodology (RSM) was employed to optimize enzyme immobilization and evaluate the optimum temperature and pH for free and immobilized enzyme. The optimal immobilization conditions observed were 150 min incubation time, pH 4.76, and an enzyme/support ratio of 1282 U/g support. Optimal activity temperature for free and immobilized enzyme was found to be 68°C and 52°C, respectively. Optimal activity pH for free and immobilized lipase was pH 4.6 and 6.0, respectively. Lipase immobilization resulted in improved enzyme stability in the presence of nonionic detergents, at high temperatures, at acidic and neutral pH, and at high concentrations of organic solvents such as 2-propanol, methanol, and acetone. PMID:22315670

  8. Characterization of DNA polymerase X from Thermus thermophilus HB8 reveals the POLXc and PHP domains are both required for 3'-5' exonuclease activity.

    PubMed

    Nakane, Shuhei; Nakagawa, Noriko; Kuramitsu, Seiki; Masui, Ryoji

    2009-04-01

    The X-family DNA polymerases (PolXs) comprise a highly conserved DNA polymerase family found in all kingdoms. Mammalian PolXs are known to be involved in several DNA-processing pathways including repair, but the cellular functions of bacterial PolXs are less known. Many bacterial PolXs have a polymerase and histidinol phosphatase (PHP) domain at their C-termini in addition to a PolX core (POLXc) domain, and possess 3'-5' exonuclease activity. Although both domains are highly conserved in bacteria, their molecular functions, especially for a PHP domain, are unknown. We found Thermus thermophilus HB8 PolX (ttPolX) has Mg(2+)/Mn(2+)-dependent DNA/RNA polymerase, Mn(2+)-dependent 3'-5' exonuclease and DNA-binding activities. We identified the domains of ttPolX by limited proteolysis and characterized their biochemical activities. The POLXc domain was responsible for the polymerase and DNA-binding activities but exonuclease activity was not detected for either domain. However, the POLXc and PHP domains interacted with each other and a mixture of the two domains had Mn(2+)-dependent 3'-5' exonuclease activity. Moreover, site-directed mutagenesis revealed catalytically important residues in the PHP domain for the 3'-5' exonuclease activity. Our findings provide a molecular insight into the functional domain organization of bacterial PolXs, especially the requirement of the PHP domain for 3'-5' exonuclease activity.

  9. Helix–hairpin–helix protein MJ1434 from Methanocaldococcus jannaschii and EndoIV homologue TTC0482 from Thermus thermophilus HB27 do not process DNA uracil residues

    PubMed Central

    Schomacher, Lars; Smolorz, Sabine; Ciirdaeva, Elena; Ber, Svetlana; Kramer, Wilfried; Fritz, Hans-Joachim

    2010-01-01

    The mutagenic threat of hydrolytic DNA cytosine deamination is met mostly by uracil DNA glycosylases (UDG) initiating base excision repair. However, several sequenced genomes of archaeal organisms are devoid of genes coding for homologues of the otherwise ubiquitous UDG superfamily of proteins. Previously, two possible solutions to this problem were offered by (i) a report of a newly discovered family of uracil DNA glycosylases exemplified by MJ1434, a protein found in the hyperthermophilic archaeon Methanocaldococcus jannaschii, and (ii) the description of TTC0482, an EndoIV homologue from the hyperthermophilic bacterium Thermus thermophilus HB27, as being able to excise uracil from DNA. Sequence homologues of both proteins can be found throughout the archaeal domain of life. Three proteins orthologous to MJ1434 and the family founder itself were tested for but failed to exhibit DNA uracil glycosylase activity when produced in an Ung-deficient Escherichia coli host. Likewise, no DNA uracil processing activity could be detected to be associated with TTC0482, while the protein was fully active as an AP endonuclease. We propose that the uracil processing activities formerly found were due to contaminations with Ung enzyme. Use of Δung-strains as hosts for production of putatively DNA-U processing enzymes provides a simple safeguard. PMID:20410075

  10. Thermostable multicopper oxidase from Thermus thermophilus HB27: crystallization and preliminary X-ray diffraction analysis of apo and holo forms

    PubMed Central

    Serrano-Posada, Hugo; Valderrama, Brenda; Stojanoff, Vivian; Rudiño-Piñera, Enrique

    2011-01-01

    A thermostable multicopper oxidase from Thermus thermophilus HB27 (Tth-MCO) was successfully crystallized using the sitting-drop and hanging-drop vapour-diffusion methods. Crystallization conditions and preliminary X-ray diffraction data to 1.5 Å resolution obtained using synchrotron radiation at 100 K are reported. The crystals belonged to space group C2221, with unit-cell parameters a = 93.6, b = 110.3, c = 96.3 Å. A monomer in the asymmetric unit yielded a Matthews coefficient (V M) of 2.60 Å3 Da−1 and a solvent content of 53%. An inactive enzyme form, apo-Tth-MCO, was also crystallized and diffraction data were collected to 1.7 Å resolution. In addition, a second inactive form of the enzyme, Hg-Tth-MCO, was obtained by soaking apo-Tth-MCO crystals with mercury(II) chloride and data were collected to a resolution of 1.7 Å. PMID:22139175

  11. Hyperhemolytic Syndrome Complicating a Delayed Hemolytic Transfusion Reaction due to anti-P1 Alloimmunization, in a Pregnant Woman with HbO-Arab/β-Thalassemia

    PubMed Central

    Bezirgiannidou, Zoe; Christoforidou, Anna; Kontekaki, Eftychia; Anastasiadis, Athanasios G; Papamichos, Spyros I.; Menexidou, Helen; Margaritis, Dimitrios; Martinis, Georges; Mantadakis, Elpis

    2016-01-01

    Background Hyperhemolytic Syndrome or Hyperhemolytic Transfusion Reaction (HHTR), a life-threatening subset of Delayed Hemolytic Transfusion Reaction (DHTR) is characterized by destruction of both transfused and autologous erythrocytes evidenced by a fall in post transfusion hemoglobin below the pre-transfusion level. Case report We describe a case of DHTR due to anti-P1 alloimmunization manifesting with hyperhemolysis in a 30-year-old Greek Pomak woman with thalassemia intermedia (HbO-Arab/β-thalassemia), during the11th week of her first gestation. She was successfully managed with avoidance of further transfusions and administration of IVIG and corticosteroids. Conclusion A high index of suspicion for HHTR is of vital importance among clinicians especially since optimal methods for its prevention and treatment remain yet to be defined. Early recognition of HHTR leading to prompt cessation of additional transfusions and initiation of immunosuppressive treatment can be life-saving, especially in clinical settings where limited therapeutic options are available, such as in pregnancy. PMID:27872733

  12. Shifting from glucose diagnosis to the new HbA1c diagnosis reduces the capability of the Finnish Diabetes Risk Score (FINDRISC) to screen for glucose abnormalities within a real-life primary healthcare preventive strategy

    PubMed Central

    2013-01-01

    Background To investigate differences in the performance of the Finnish Diabetes Risk Score (FINDRISC) as a screening tool for glucose abnormalities after shifting from glucose-based diagnostic criteria to the proposed new hemoglobin (Hb)A1c-based criteria. Methods A cross-sectional primary-care study was conducted as the first part of an active real-life lifestyle intervention to prevent type 2 diabetes within a high-risk Spanish Mediterranean population. Individuals without diabetes aged 45-75 years (n = 3,120) were screened using the FINDRISC. Where feasible, a subsequent 2-hour oral glucose tolerance test and HbA1c test were also carried out (n = 1,712). The performance of the risk score was calculated by applying the area under the curve (AUC) for the receiver operating characteristic, using three sets of criteria (2-hour glucose, fasting glucose, HbA1c) and three diagnostic categories (normal, pre-diabetes, diabetes). Results Defining diabetes by a single HbA1c measurement resulted in a significantly lower diabetes prevalence (3.6%) compared with diabetes defined by 2-hour plasma glucose (9.2%), but was not significantly lower than that obtained using fasting plasma glucose (3.1%). The FINDRISC at a cut-off of 14 had a reasonably high ability to predict diabetes using the diagnostic criteria of 2-hour or fasting glucose (AUC = 0.71) or all glucose abnormalities (AUC = 0.67 and 0.69, respectively). When HbA1c was used as the primary diagnostic criterion, the AUC for diabetes detection dropped to 0.67 (5.6% reduction in comparison with either 2-hour or fasting glucose) and fell to 0.55 for detection of all glucose abnormalities (17.9% and 20.3% reduction, respectively), with a relevant decrease in sensitivity of the risk score. Conclusions A shift from glucose-based diagnosis to HbA1c-based diagnosis substantially reduces the ability of the FINDRISC to screen for glucose abnormalities when applied in this real-life primary-care preventive strategy. PMID

  13. Association between knowledge, locus of control and health belief with self-management, Hb A1c level and number of attendances in type 1 diabetes mellitus patients

    PubMed Central

    Mansour-Ghanaei, Roya; Joukar, Farahnaz; Soati, Fatemeh; Khanegha, Atefeh Ghanbari

    2013-01-01

    This survey was designed to determine the association between knowledge, locus of control and health belief with self-management, Hb A1c level and Number of attendances in type 1 diabetic patients in Rasht, Guilan Province - North of Iran. Data was derived from chart reviews of 92 patients. Patients’ glycosylated hemoglobin level and their number of health care attendances during the last 6 months were recorded. The four part questionnaires covered patients’ demographic data, knowledge, perceived control and health belief of diabetes. A blood sample was taken from each patient. There was no significant relationship between demographic data such as gender, age, marital status, education, occupation, duration of the disease, place of living and family history with knowledge, health belief and locus of control (P > 0.05). Also the results didn’t show any significant association between the complicated group and their knowledge and health belief (P > 0.05) while it was significantly related to their locus of control (P < 0.004). The majority of the samples had poor knowledge (59.8%), health belief (71.7%) and locus of control (62%). There was no significant relationship between patients’ knowledge, health belief and locus of control with their glycosylated hemoglobin level, number of referrals and self-management. It is suggested by the present survey that locus of control, health belief and knowledge of patients are not found to have no practical effect upon diabetic self-management behavior or outcomes, according to the variables used and care for the diabetic patients must be tailored to individual requirements. PMID:23844271

  14. QTL mapping for European corn borer resistance ( Ostrinia nubilalis Hb.), agronomic and forage quality traits of testcross progenies in early-maturing European maize ( Zea mays L.) germplasm.

    PubMed

    Papst, C; Bohn, M; Utz, H F; Melchinger, A E; Klein, D; Eder, J

    2004-05-01

    In hybrid breeding the performance of lines in hybrid combinations is more important than their performance per se. Little information is available on the correlation between individual line and testcross (TC) performances for the resistance to European corn borer (ECB, Ostrinia nubilalis Hb.) in maize ( Zea mays L.). Marker assisted selection (MAS) will be successful only if quantitative trait loci (QTL) found in F(2) derived lines for ECB resistance are still expressed in hybrid combinations. The objectives of our study were: (1) to identify and characterize QTL for ECB resistance as well as agronomic and forage quality traits in a population of testcrossed F(2:3) families; (2) to evaluate the consistency of QTL for per se and TC performances; and (3) to determine the association between per se and TC performances of F(2:3) lines for these traits. Two hundred and four F(2:3) lines were derived from the cross between maize lines D06 (resistant) and D408 (susceptible). These lines were crossed to D171 and the TC progenies were evaluated for ECB resistance and agronomic performance in two locations in 2000 and 2001. Using these TC progenies, six QTL for stalk damage rating (SDR) were found. These QTL explained 27.4% of the genotypic variance in a simultaneous fit. Three QTL for SDR were detected consistently for per se and TC performance. Phenotypic and genotypic correlations were low for per se and TC performance for SDR. Correlations between SDR and quality traits were not significant. Based on these results, we conclude that MAS will not be an efficient method for improving SDR. However, new molecular tools might provide the opportunity to use QTL data as a first step to identify genes involved in ECB resistance. Efficient MAS procedures might then be based on markers designed to trace and to combine specific genes and their alleles in elite maize breeding germplasm.

  15. Austrian Moderate Altitude Study (AMAS 2000): erythropoietic activity and Hb-O(2) affinity during a 3-week hiking holiday at moderate altitude in persons with metabolic syndrome.

    PubMed

    Schobersberger, Wolfgang; Greie, Sven; Humpeler, Egon; Mittermayr, Markus; Fries, Dietmar; Schobersberger, Beatrix; Artner-Dworzak, Erika; Hasibeder, Walter; Klingler, Anton; Gunga, Hanns-Christian

    2005-01-01

    Moderate altitude hypoxia (1500 to 2500 m) is known to stimulate erythropoiesis and to improve oxygen transport to tissue by a reduction of Hb-O(2) affinity. Whether this adaptation also occurs in tourists with metabolic syndrome has not yet been investigated sufficiently. Thus, we performed a prospective field study to measure erythropoietic parameters and oxygen transport properties in 24 male volunteers with metabolic syndrome during a 3- week holiday program at 1700 m consisting of four guided, individually adapted hiking tours per week. The following examinations were performed: baseline investigations at 500 m (T1); examinations at moderate altitude on day 1 (T2), day 4 (T3), day 9 (T4), and day 19 (T5); and postaltitude tests (T6) 7 to 10 days after return. On day 1 and day 19, a walk on a standardized hiking test route with oxygen saturation (SpO(2)) measure points was performed. Hemoglobin, packed cell volume, and red cell count showed changes over time, with higher values at T5 as compared to baseline. Reticulocyte count and erythropoietin (EPO) were increased at T2 and increased further until T5. EPO declined toward prealtitude values. P50-value (blood PO(2) at 50% hemoglobin oxygen saturation at actual pH) increased during the altitude sojourn (maximum increase at T5 by +0.40 kPa). At T5 all volunteers had a higher SpO(2) before, during, and at the end of the test route compared to T1. During adaptation to moderate altitude, persons with metabolic syndrome exhibit an increase in EPO and a rightward shift of the oxygen dissociation curve that is similar to healthy subjects.

  16. Nuclear magnetic resonance structure of the cytoplasmic tail of heparin binding EGF-like growth factor (proHB-EGF-CT) complexed with the ubiquitin homology domain of Bcl-2-associated athanogene 1 from Mus musculus (mBAG-1-UBH).

    PubMed

    Hung, Kuo-Wei; Huang, Hsiao-Wen; Cho, Ching-Chang; Chang, Sheng-Chieh; Yu, Chin

    2014-04-01

    The membrane form of heparin binding EGF-like growth factor (proHB-EGF) yields secreted HB-EGF and a membrane-anchored cytoplasmic tail (proHB-EGF-CT), which may be targeted to the nuclear membrane after a shedding stimulus. Bcl-2-associated athanogene 1 (BAG-1) accumulates in the nuclei and inhibits apoptosis in adenoma-derived cell lines. The maintenance of high levels of nuclear BAG-1 enhances cell survival. However, the ubiquitin homology domain of BAG-1 from Mus musculus (mBAG-1-UBH) is proposed to interact with proHB-EGF-CT, and this interaction may enhance the cytoprotection against the apoptosis inducer. The mechanism of the synergistic anti-apoptosis function of proHB-EGF-CT and mBAG-1-UBH is still unknown. We offer a hypothesis that proHB-EGF-CT can maintain high levels of nuclear BAG-1. In this study, we first report the three-dimensional nuclear magnetic resonance structure of proHB-EGF-CT complexed with mBAG-1-UBH. In the structure of the complex, the residues in the C-terminus and one turn between β-strands β1 and β2 of mBAG-1-UBH bind to two terminals of proHB-EGF-CT, which folds into a loop with end-to-end contact. This end-to-end folding of proHB-EGF-CT causes the basic amino acids to colocalize and form a positively charged groove. The dominant forces in the binding interface between proHB-EGF-CT and mBAG-1-UBH are charge-charge interactions. On the basis of our mutagenesis results, the basic amino acid cluster in the N-terminus of proHB-EGF-CT is the crucial binding site for mBAG-1-UBH, whereas another basic amino acid in the C-terminus facilitates this interaction. Interestingly, the mBAG-1-UBH binding region on the proHB-EGF-CT peptide is also involved in the region found to be important for nuclear envelope targeting, supporting the hypothesis that proHB-EGF-CT is most likely able to trigger the nuclear translocation of BAG-1 in keeping its level high.

  17. Energy Scan of the e+e-→hb(n P )π+π- (n =1 , 2) Cross Sections and Evidence for ϒ (11020 ) Decays into Charged Bottomoniumlike States

    NASA Astrophysics Data System (ADS)

    Mizuk, R.; Bondar, A.; Adachi, I.; Aihara, H.; Asner, D. M.; Atmacan, H.; Aulchenko, V.; Aushev, T.; Ayad, R.; Badhrees, I.; Bakich, A. M.; Barberio, E.; Behera, P.; Bhardwaj, V.; Bhuyan, B.; Biswal, J.; Bobrov, A.; Bonvicini, G.; Bozek, A.; Bračko, M.; Browder, T. E.; Červenkov, D.; Chekelian, V.; Chen, A.; Cheon, B. G.; Chilikin, K.; Chistov, R.; Chobanova, V.; Choi, S.-K.; Choi, Y.; Cinabro, D.; Dalseno, J.; Danilov, M.; Dash, N.; Doležal, Z.; Drutskoy, A.; Eidelman, S.; Epifanov, D.; Ferber, T.; Fulsom, B. G.; Gaur, V.; Garmash, A.; Gillard, R.; Goh, Y. M.; Goldenzweig, P.; Golob, B.; Greenwald, D.; Hara, T.; Hayasaka, K.; Hayashii, H.; Hou, W.-S.; Hsu, C.-L.; Inami, K.; Inguglia, G.; Ishikawa, A.; Iwasaki, Y.; Jaegle, I.; Julius, T.; Kang, K. H.; Katrenko, P.; Kim, D. Y.; Kim, H. J.; Kim, J. B.; Kim, K. T.; Kim, M. J.; Kim, S. H.; Kim, Y. J.; Kinoshita, K.; Kodyš, P.; Korpar, S.; Kotchetkov, D.; Krokovny, P.; Kuhr, T.; Kuzmin, A.; Kwon, Y.-J.; Lange, J. S.; Li, C. H.; Li, H.; Li, L.; Li Gioi, L.; Libby, J.; Liventsev, D.; Lubej, M.; Luo, T.; Masuda, M.; Matsuda, T.; Matvienko, D.; Miyabayashi, K.; Miyata, H.; Mohanty, G. B.; Moll, A.; Nakano, E.; Nakao, M.; Nanut, T.; Nath, K. J.; Negishi, K.; Niiyama, M.; Nisar, N. K.; Nishida, S.; Ogawa, S.; Okuno, S.; Olsen, S. L.; Onuki, Y.; Pakhlov, P.; Pakhlova, G.; Pal, B.; Park, C. W.; Park, H.; Paul, S.; Pedlar, T. K.; Pestotnik, R.; Petrič, M.; Piilonen, L. E.; Pulvermacher, C.; Ritter, M.; Sakai, Y.; Sandilya, S.; Sanuki, T.; Savinov, V.; Schlüter, T.; Schneider, O.; Schnell, G.; Schwanda, C.; Seino, Y.; Semmler, D.; Senyo, K.; Seon, O.; Sevior, M. E.; Shebalin, V.; Shibata, T.-A.; Shiu, J.-G.; Shwartz, B.; Simon, F.; Solovieva, E.; Starič, M.; Stypula, J.; Sumiyoshi, T.; Takizawa, M.; Tamponi, U.; Tanida, K.; Teramoto, Y.; Tikhomirov, I.; Trabelsi, K.; Uchida, M.; Uglov, T.; Unno, Y.; Uno, S.; Urquijo, P.; Usov, Y.; Van Hulse, C.; Varner, G.; Vorobyev, V.; Wang, C. H.; Wang, M.-Z.; Wang, P.; Wang, X. L.; Watanabe, Y.; Williams, K. M.; Won, E.; Yamaoka, J.; Yamashita, Y.; Yelton, J.; Yuan, C. Z.; Zhang, Z. P.; Zhilich, V.; Zhukova, V.; Zhulanov, V.; Zupanc, A.; Belle Collaboration

    2016-09-01

    Using data collected with the Belle detector at the KEKB asymmetric-energy e+e- collider, we measure the energy dependence of the e+e-→hb(n P )π+π- (n =1 , 2) cross sections from thresholds up to 11.02 GeV. We find clear ϒ (10860 ) and ϒ (11020 ) peaks with little or no continuum contribution. We study the resonant substructure of the ϒ (11020 )→hb(n P )π+π- transitions and find evidence that they proceed entirely via the intermediate isovector states Zb(10610 ) and Zb(10650 ). The relative fraction of these states is loosely constrained by the current data: The hypothesis that only Zb(10610 ) is produced is excluded at the level of 3.3 standard deviations, while the hypothesis that only Zb(10650 ) is produced is not excluded at a significant level.

  18. Impact of age, BMI and HbA1c levels on the genome-wide DNA methylation and mRNA expression patterns in human adipose tissue and identification of epigenetic biomarkers in blood.

    PubMed

    Rönn, Tina; Volkov, Petr; Gillberg, Linn; Kokosar, Milana; Perfilyev, Alexander; Jacobsen, Anna Louisa; Jørgensen, Sine W; Brøns, Charlotte; Jansson, Per-Anders; Eriksson, Karl-Fredrik; Pedersen, Oluf; Hansen, Torben; Groop, Leif; Stener-Victorin, Elisabet; Vaag, Allan; Nilsson, Emma; Ling, Charlotte

    2015-07-01

    Increased age, BMI and HbA1c levels are risk factors for several non-communicable diseases. However, the impact of these factors on the genome-wide DNA methylation pattern in human adipose tissue remains unknown. We analyzed the DNA methylation of ∼480 000 sites in human adipose tissue from 96 males and 94 females and related methylation to age, BMI and HbA1c. We also compared epigenetic signatures in adipose tissue and blood. Age was significantly associated with both altered DNA methylation and expression of 1050 genes (e.g. FHL2, NOX4 and PLG). Interestingly, many reported epigenetic biomarkers of aging in blood, including ELOVL2, FHL2, KLF14 and GLRA1, also showed significant correlations between adipose tissue DNA methylation and age in our study. The most significant association between age and adipose tissue DNA methylation was found upstream of ELOVL2. We identified 2825 genes (e.g. FTO, ITIH5, CCL18, MTCH2, IRS1 and SPP1) where both DNA methylation and expression correlated with BMI. Methylation at previously reported HIF3A sites correlated significantly with BMI in females only. HbA1c (range 28-46 mmol/mol) correlated significantly with the methylation of 711 sites, annotated to, for example, RAB37, TICAM1 and HLA-DPB1. Pathway analyses demonstrated that methylation levels associated with age and BMI are overrepresented among genes involved in cancer, type 2 diabetes and cardiovascular disease. Our results highlight the impact of age, BMI and HbA1c on epigenetic variation of candidate genes for obesity, type 2 diabetes and cancer in human adipose tissue. Importantly, we demonstrate that epigenetic biomarkers in blood can mirror age-related epigenetic signatures in target tissues for metabolic diseases such as adipose tissue.

  19. Insulin induces a transcriptional activation of epiregulin, HB-EGF and amphiregulin, by a PI3K-dependent mechanism: Identification of a specific insulin-responsive promoter element

    SciTech Connect

    Ornskov, Dorthe; Nexo, Ebba; Sorensen, Boe S. . E-mail: boess@as.aaa.dk

    2007-03-23

    Previously we have shown that insulin-stimulation of RT4 bladder cancer cells leads to increased proliferation, which require HER1 activation, and is accompanied by increased mRNA expression of the EGF-ligands heparin-binding EGF-like growth factor (HB-EGF), amphiregulin (AR), and epiregulin (EPI) [D. Ornskov, E. Nexo, B.S. Sorensen, Insulin-induced proliferation of bladder cancer cells is mediated through activation of the epidermal growth factor system, FEBS J. 273 (2006) 5479-5489]. In the present paper, we have investigated the molecular mechanism leading to this insulin-induced expression. We monitored the decay of mRNA after inhibiting transcription with Actinomycin D and demonstrated that the insulin-mediated increase was not caused by enhanced mRNA stability. In untreated cells, HB-EGF mRNA was the least stable, whereas AR and EPI mRNA decayed with slower kinetics. However, promoter analysis of HB-EGF and EPI demonstrated that insulin stimulated transcription. Studies on the EPI promoter identified the insulin-responsive element to be located in the region -564 to -365 bp. This region contains potential binding sites for the transcription factors SP1, AP1, and NF-{kappa}B. Interestingly, all three transcription factors can be activated by PI3K. We demonstrate that the insulin-induced expression of HB-EGF, AR, and EPI mRNA is completely prevented by the specific PI3K inhibitor Wortmannin, suggesting an involvement of the PI3K.

  20. IncP-1β Plasmids Are Important Carriers of Fitness Traits for Variovorax Species in the Mycosphere--Two Novel Plasmids, pHB44 and pBS64, with Differential Effects Unveiled.

    PubMed

    Zhang, Miaozhi; Warmink, Jan; Pereira E Silva, Michele C; Brons, Jolanda; Smalla, Kornelia; van Elsas, Jan Dirk

    2015-07-01

    The Laccaria proxima mycosphere strongly selects Variovorax paradoxus cells. Fifteen independent V. paradoxus strains, isolated from mycospheres sampled at two occasions, were investigated with respect to the occurrence of plasmids of sizes <60-100 kb. Two V. paradoxus strains, HB44 and BS64, were found to contain such plasmids, which were coined pHB44 and pBS64. Replicon typing using a suite of plasmid-specific PCR systems indicated that both plasmids belong to the IncP-1β group. Also, both were able to mobilize selectable IncQ group plasmids into Escherichia coli as well as Pseudomonas fluorescens. Moreover, they showed stable replication in these organisms, confirming their broad host range. Strain BS64 was cured of pBS64 and plasmid pHB44 was subsequently moved into this cured strain by making use of the IncQ group tracer plasmid pSUP104, which was then removed at elevated temperature. Thus, both plasmids could be screened for their ability to confer a phenotype upon strain BS64. No evidence for the presence of genes for xenobiotic degradation and/or antibiotic or heavy metal resistances was found for either of the two plasmids. Remarkably, both could stimulate the production of biofilm material by strain BS64. Also, the population densities of pBS64-containing strain BS64 were temporarily raised in liquid as well as soil systems (versus the plasmid-cured strain), both in the presence of the fungal host Lyophyllum sp. strain Karsten. Strikingly, plasmid pHB44 significantly enhanced the fitness of strain BS64 in soil containing Lyophyllum sp. strain Karsten, but decreased its fitness in soil supplemented with extra FeCl3. The effect was noted both in separate (no inter-strain competition) and joint (competition) inoculations.

  1. APPLICATION OF COLUMN EXTRACTION METHOD FOR IMPURITIES ANALYSIS ON HB-LINE PLUTONIUM OXIDE IN SUPPORT OF MOX FEED PRODUCT SPECIFICATIONS

    SciTech Connect

    Jones, M.; Diprete, D.; Wiedenman, B.

    2012-03-20

    The current mission at H-Canyon involves the dissolution of an Alternate Feedstocks 2 (AFS-2) inventory that contains plutonium metal. Once dissolved, HB-Line is tasked with purifying the plutonium solution via anion exchange, precipitating the Pu as oxalate, and calcining to form plutonium oxide (PuO{sub 2}). The PuO{sub 2} will provide feed product for the Mixed Oxide (MOX) Fuel Fabrication Facility, and the anion exchange raffinate will be transferred to H-Canyon. The results presented in this report document the potential success of the RE resin column extraction application on highly concentrated Pu samples to meet MOX feed product specifications. The original 'Hearts Cut' sample required a 10000x dilution to limit instrument drift on the ICP-MS method. The instrument dilution factors improved to 125x and 250x for the sample raffinate and sample eluent, respectively. As noted in the introduction, the significantly lower dilutions help to drop the total MRL for the analyte. Although the spike recoveries were half of expected in the eluent for several key elements, they were between 94-98% after Nd tracer correction. It is seen that the lower ICD limit requirements for the rare earths are attainable because of less dilution. Especially important is the extremely low Ga limit at 0.12 {mu}g/g Pu; an ICP-MS method is now available to accomplish this task on the sample raffinate. While B and V meet the column A limits, further development is needed to meet the column B limits. Even though V remained on the RE resin column, an analysis method is ready for investigation on the ICP-MS, but it does not mean that V cannot be measured on the ICP-ES at a low dilution to meet the column B limits. Furthermore, this column method can be applicable for ICP-ES as shown in Table 3-2, in that it trims the sample of Pu, decreasing and sometimes eliminating Pu spectral interferences.

  2. Association of Exposure to Radio-Frequency Electromagnetic Field Radiation (RF-EMFR) Generated by Mobile Phone Base Stations with Glycated Hemoglobin (HbA1c) and Risk of Type 2 Diabetes Mellitus.

    PubMed

    Meo, Sultan Ayoub; Alsubaie, Yazeed; Almubarak, Zaid; Almutawa, Hisham; AlQasem, Yazeed; Hasanato, Rana Muhammed

    2015-11-13

    Installation of mobile phone base stations in residential areas has initiated public debate about possible adverse effects on human health. This study aimed to determine the association of exposure to radio frequency electromagnetic field radiation (RF-EMFR) generated by mobile phone base stations with glycated hemoglobin (HbA1c) and occurrence of type 2 diabetes mellitus. For this study, two different elementary schools (school-1 and school-2) were selected. We recruited 159 students in total; 96 male students from school-1, with age range 12-16 years, and 63 male students with age range 12-17 years from school-2. Mobile phone base stations with towers existed about 200 m away from the school buildings. RF-EMFR was measured inside both schools. In school-1, RF-EMFR was 9.601 nW/cm² at frequency of 925 MHz, and students had been exposed to RF-EMFR for a duration of 6 h daily, five days in a week. In school-2, RF-EMFR was 1.909 nW/cm² at frequency of 925 MHz and students had been exposed for 6 h daily, five days in a week. 5-6 mL blood was collected from all the students and HbA1c was measured by using a Dimension Xpand Plus Integrated Chemistry System, Siemens. The mean HbA1c for the students who were exposed to high RF-EMFR was significantly higher (5.44 ± 0.22) than the mean HbA1c for the students who were exposed to low RF-EMFR (5.32 ± 0.34) (p = 0.007). Moreover, students who were exposed to high RF-EMFR generated by MPBS had a significantly higher risk of type 2 diabetes mellitus (p = 0.016) relative to their counterparts who were exposed to low RF-EMFR. It is concluded that exposure to high RF-EMFR generated by MPBS is associated with elevated levels of HbA1c and risk of type 2 diabetes mellitus.

  3. Association of Exposure to Radio-Frequency Electromagnetic Field Radiation (RF-EMFR) Generated by Mobile Phone Base Stations with Glycated Hemoglobin (HbA1c) and Risk of Type 2 Diabetes Mellitus

    PubMed Central

    Meo, Sultan Ayoub; Alsubaie, Yazeed; Almubarak, Zaid; Almutawa, Hisham; AlQasem, Yazeed; Muhammed Hasanato, Rana

    2015-01-01

    Installation of mobile phone base stations in residential areas has initiated public debate about possible adverse effects on human health. This study aimed to determine the association of exposure to radio frequency electromagnetic field radiation (RF-EMFR) generated by mobile phone base stations with glycated hemoglobin (HbA1c) and occurrence of type 2 diabetes mellitus. For this study, two different elementary schools (school-1 and school-2) were selected. We recruited 159 students in total; 96 male students from school-1, with age range 12–16 years, and 63 male students with age range 12–17 years from school-2. Mobile phone base stations with towers existed about 200 m away from the school buildings. RF-EMFR was measured inside both schools. In school-1, RF-EMFR was 9.601 nW/cm2 at frequency of 925 MHz, and students had been exposed to RF-EMFR for a duration of 6 h daily, five days in a week. In school-2, RF-EMFR was 1.909 nW/cm2 at frequency of 925 MHz and students had been exposed for 6 h daily, five days in a week. 5–6 mL blood was collected from all the students and HbA1c was measured by using a Dimension Xpand Plus Integrated Chemistry System, Siemens. The mean HbA1c for the students who were exposed to high RF-EMFR was significantly higher (5.44 ± 0.22) than the mean HbA1c for the students who were exposed to low RF-EMFR (5.32 ± 0.34) (p = 0.007). Moreover, students who were exposed to high RF-EMFR generated by MPBS had a significantly higher risk of type 2 diabetes mellitus (p = 0.016) relative to their counterparts who were exposed to low RF-EMFR. It is concluded that exposure to high RF-EMFR generated by MPBS is associated with elevated levels of HbA1c and risk of type 2 diabetes mellitus. PMID:26580639

  4. TECHNICAL BASIS FOR DOE STANDARD 3013 EQUIVALENCY SUPPORTING REDUCED TEMPERATURE STABILIZATION OF OXALATE-DERIVED PLUTONIUM OXIDE PRODUCED BY THE HB-LINE FACILITY AT SAVANNAH RIVER SITE

    SciTech Connect

    Duffey, J.; Livingston, R.; Berg, J.; Veirs, D.

    2012-07-02

    The HB-Line (HBL) facility at the Savannah River Site (SRS) is designed to produce high-purity plutonium dioxide (PuO{sub 2}) which is suitable for future use in production of Mixed Oxide (MOX) fuel. The MOX Fuel Fabrication Facility (MFFF) requires PuO{sub 2} feed to be packaged per the U.S. Department of Energy (DOE) Standard 3013 (DOE-STD-3013) to comply with the facility's safety basis. The stabilization conditions imposed by DOE-STD-3013 for PuO{sub 2} (i.e., 950 C for 2 hours) preclude use of the HBL PuO{sub 2} in direct fuel fabrication and reduce the value of the HBL product as MFFF feedstock. Consequently, HBL initiated a technical evaluation to define acceptable operating conditions for production of high-purity PuO{sub 2} that fulfills the DOE-STD-3013 criteria for safe storage. The purpose of this document is to demonstrate that within the defined operating conditions, the HBL process will be equivalent for meeting the requirements of the DOE-STD-3013 stabilization process for plutonium-bearing materials from the DOE complex. The proposed 3013 equivalency reduces the prescribed stabilization temperature for high-purity PuO{sub 2} from oxalate precipitation processes from 950 C to 640 C and places a limit of 60% on the relative humidity (RH) at the lowest material temperature. The equivalency is limited to material produced using the HBL established flow sheet, for example, nitric acid anion exchange and Pu(IV) direct strike oxalate precipitation with stabilization at a minimum temperature of 640 C for four hours (h). The product purity must meet the MFFF acceptance criteria of 23,600 {micro}g/g Pu (i.e., 2.1 wt %) total impurities and chloride content less than 250 {micro}g/g of Pu. All other stabilization and packaging criteria identified by DOE-STD-3013-2012 or earlier revisions of the standard apply. Based on the evaluation of test data discussed in this document, the expert judgment of the authors supports packaging the HBL product under a 3013

  5. Carotid Intima-Media Thickness and Visit-to-Visit HbA1c Variability Predict Progression of Chronic Kidney Disease in Type 2 Diabetic Patients with Preserved Kidney Function

    PubMed Central

    Takenouchi, Akiko; Tsuboi, Ayaka; Kurata, Miki; Fukuo, Keisuke

    2016-01-01

    Background/Aims. Subclinical atherosclerosis and long-term glycemic variability have been reported to predict incident chronic kidney disease (CKD) in the general population. However, these associations have not been investigated in patients with type 2 diabetes with preserved kidney function. Methods. We prospectively followed up 162 patients with type 2 diabetes (mean age, 62.3 years; 53.6% men) and assessed whether carotid intima-media thickness (IMT) measured by B-mode ultrasound and visit-to-visit HbA1c variability are associated with deterioration of CKD (incident CKD defined as estimated GFR [eGFR] < 60 mL/min/1.73 m2 and progression of CKD stages) over a median follow-up of 6.0 years. At baseline, 25 patients (15.4%) had CKD. Cox proportional hazards regression models were used for identifying associated factors of CKD deterioration. Results. Estimated GFR decreased from 75.8 ± 16.3 to 67.4 ± 18.2 mL/min/1.73 m2 (p < 0.01). Of 162 patients, 32 developed CKD and 8 made a progression of CKD stages. Multivariate Cox regression analysis revealed that carotid IMT (HR: 4.0, 95% CI: 1.1–14.226.7, and p = 0.03) and coefficient of variation of HbA1c (HR: 1.12, 95%: 1.04–1.21, and p = 0.003) were predictors of deterioration of CKD independently of age, mean HbA1c, urinary albumin/creatinine ratio, baseline eGFR, uric acid, and leucocyte count. Conclusions. Subclinical atherosclerosis and long-term glycemic variability predict deterioration of chronic kidney disease (as defined by incident or worsening CKD) in type 2 diabetic patients with preserved kidney function. PMID:28090540

  6. A Comparison Between the Effect of Cuminum Cyminum and Vitamin E on the Level of Leptin, Paraoxonase 1, HbA1c and Oxidized LDL in Diabetic Patients

    PubMed Central

    Samani Keihan, Ghatreh; Gharib, Mohammad Hossein; Momeni, Ali; Hemati, Zohreh; Sedighin, Roya

    2016-01-01

    Diabetes is one of the most common metabolic diseases in the world. Vitamin E reduces protein glycation and improves insulin sensitivity, while cumin is effective in remission of diabetes. Therefore this study was designed to evaluate the effects of vitamin E and cumin essential oil, on the blood level of leptin,glycosylated hemoglobin (HbA1C) and also on lipid profile in diabetic patients.In this double blind clinical trial, 95 diabetic patients were selected and randomly dividedinto three groups.The first group received cumin essential oil in capsule form. The second group received Vitamin E, and the third group was used ascontrol receiving oral gelatin capsules as placebo for three months period.Blood glucose, lipid profile, apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), leptin, HbA1c, oxidized LDL (oxLDL), and paraoxonase1 activity were measured. The results showed reduction in oxLDL and significant increase in paraoxonase 1 in Vitamin E group by the end of the third month period (P<0.05). Cumin group showed decrease in blood glucose, HbA1C, triglyceride, leptin and ox-LDL. ApoA1 and paraoxonase1 were also increased by cumin treatment (P<0.05).Diabetic complications may have been reduced by intake of Vitamin E and cumin essential oil. Cumin in comparison with vitamin E has broader impact and it is more beneficial in terms of ability to reduce the diabetic index. PMID:28357199

  7. [Diagnostic value of fasting glucose, fructosamine, and glycated haemoglobin HbA(1c) with regard to ADA 1997 and who 1998 criteria for detecting diabetes and other glucose tolerance abnormalities].

    PubMed

    Gołembiewska, Edyta

    2004-01-01

    New diagnostic criteria for diabetes mellitus proposed by the American Diabetes Association in 1997 and the World Heath Organization Consultation Report in 1998 recommend lowering of the fasting plasma glucose (FPG) to 7.0 mmol/L. This change in the diagnostic FPG cut-off point was based on the results of well-documented epidemiological studies showing that increased risk of microangiopathy starts at values closer to 7.0 than 7.8 mmol/L used in the past. To facilitate the diagnosis, ADA Expert Committee recommends using FPG as the main diagnostic tool and eliminating OGTT from routine clinical practice. In contrast to ADA, WHO Consultation Group strongly recommended keeping OGTT in routine use. Due to the inconvenience, poor reproducibility, non-physiological character and labour-intensiveness of OGTT, an alternative test has been sought. The aim of this study was to determine whether fasting capillary glucose (FCG) along with fructosamine and glycated haemoglobin (HbA(1c)) perform better for the detection of glucose tolerance abnormalities than FCG alone. OGTT was performed in 1528 patients. Serum fructosamine was determined in 480 and glycated haemoglobin in 234 of these patients. To assess the value of FCG, fructosamine and glycated haemoglobin in predicting post-load glycaemia and detecting glucose tolerance abnormalities, multiple linear regression analysis and Receiver Operating Characteristics analysis were done. Fructosamine correlated stronger with 2h-postload glucose concentrations than with fasting glucose. HbA(1c) correlated stronger with FCG than with 2h-postload glucose. Combined use of fructosamine and FCG predicted 2h-postload glucose better than combined use of FCG and HbA(1c). Receiver Operating Characteristics curve analysis showed that FCG was the best criterion in discriminating diabetes. Combined use of FCG and fructosamine slightly improved the ability to discriminate glucose tolerance abnormalities from normal glucose tolerance. The

  8. The difference between oats and beta-glucan extract intake in the management of HbA1c, fasting glucose and insulin sensitivity: a meta-analysis of randomized controlled trials.

    PubMed

    He, Li-xia; Zhao, Jian; Huang, Yuan-sheng; Li, Yong

    2016-03-01

    Increasing oats and beta-glucan extract intake has been associated with improved glycemic control, which is associated with the reduction in the development of diabetes. This study aims to assess the different effects between oat (whole and bran) and beta-glucan extract intake on glycemic control and insulin sensitivity. PubMed, Embase, Medline, The Cochrane Library, CINAHL and Web of Science were searched up to February 2014. We included randomized controlled trials with interventions that lasted at least four weeks that compared oats and beta-glucan (extracted from oats or other sources) intake with a control. A total of 1351 articles were screened for eligibility, and relevant data were extracted from 18 studies (n = 1024). Oat product dose ranged from 20 g d(-1) to 136 g d(-1), and beta-glucan extract dose ranged from 3 g d(-1) to 10 g d(-1). Compared with the control, oat intake resulted in a greater decrease in fasting glucose and insulin of subjects (P < 0.05), but beta-glucan extract intake did not. Furthermore, oat intake resulted in a greater decrease in glycosylated hemoglobin (HbA1c) (P < 0.001, I(2) = 0%) and fasting glucose (P < 0.001, I(2) = 68%) after removing one study using a concentrate and a different design and fasting insulin of type 2 diabetes (T2D) (P < 0.001, I(2) = 0%). The intake of oats and beta-glucan extracted from oats were effective in decreasing fasting glucose (P = 0.007, I(2) = 91%) and fasting insulin of T2D (P < 0.001, I(2) = 0%) and tented to lower HbA1c (P = 0.09, I(2) = 92%). Higher consumption of whole oats and oat bran, but not oat or barley beta-glucan extracts, are associated with lower HbA1c, fasting glucose and fasting insulin of T2D, hyperlipidaemic and overweight subjects, especially people with T2D, which supports the need for clinical trials to evaluate the potential role of oats in approaching to the management of glycemic control and insulin sensitivity of diabetes or metabolic syndrome subjects.

  9. Effect of long-term intermittent supplementation with multiple micronutrients compared with iron-and-folic acid supplementation on Hb and micronutrient status of non-anaemic adolescent schoolgirls in rural Bangladesh.

    PubMed

    Ahmed, Faruk; Khan, Moududur R; Akhtaruzzaman, Mohammad; Karim, Rezaul; Williams, Gail; Banu, Cadi P; Nahar, Badrun; Darnton-Hill, Ian

    2012-10-28

    The present study examined whether long-term supplementation with once- and twice-weekly multiple micronutrients (MMN-1 and MMN-2) can improve Hb and micronutrient status more than twice-weekly Fe-folic acid (IFA-2) supplementation in non-anaemic adolescent girls in Bangladesh. An equal number of 324 rural schoolgirls aged 11-17 years were given MMN-1 or MMN-2 or IFA-2 supplements for 52 weeks in a randomised, double-blind trial. Blood samples were collected at baseline, and at 26 and 52 weeks of supplementation. The girls receiving IFA-2 supplements were more likely to be anaemic than the girls receiving MMN-2 supplements for 26 weeks (OR 5·1, 95% CI 1·3, 19·5; P = 0·018). All three supplements reduced Fe deficiency effectively. Both the MMN-1 and MMN-2 groups showed significantly greater improvements in vitamins A, B(2) and C status than the girls in the IFA-2 group, as might be expected. Receiving a MMN-1 supplement was found to be less effective than MMN-2 supplement in improving Fe, vitamins A, B(2) and folic acid status. Receiving micronutrient supplements beyond 26 weeks showed little additional benefit in improving micronutrient status. In conclusion, given twice-weekly for 26 weeks, MMN supplements can improve micronutrient status effectively with no significant increase in Hb concentration compared with IFA supplements in non-anaemic Bangladeshi adolescent girls. However, it significantly reduces the risk of anaemia. Before any recommendations can be made, further research, including into cost-effectiveness, is needed to see whether MMN supplementation has any additional longer-term health benefits over that of IFA supplementation in this population.

  10. The cell-penetrating peptide domain from human heparin-binding epidermal growth factor-like growth factor (HB-EGF) has anti-inflammatory activity in vitro and in vivo

    SciTech Connect

    Lee, Jue-Yeon; Seo, Yoo-Na; Park, Hyun-Jung; Park, Yoon-Jeong; Chung, Chong-Pyoung

    2012-03-23

    Highlights: Black-Right-Pointing-Pointer HBP sequence identified from HB-EGF has cell penetration activity. Black-Right-Pointing-Pointer HBP inhibits the NF-{kappa}B dependent inflammatory responses. Black-Right-Pointing-Pointer HBP directly blocks phosphorylation and degradation of I{kappa}B{alpha}. Black-Right-Pointing-Pointer HBP inhibits nuclear translocation of NF-{kappa}B p65 subunit. -- Abstract: A heparin-binding peptide (HBP) sequence from human heparin-binding epidermal growth factor-like growth factor (HB-EGF) was identified and was shown to exhibit cell penetration activity. This cell penetration induced an anti-inflammatory reaction in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. HBP penetrated the cell membrane during the 10 min treatment and reduced the LPS-induced production of nitric oxide (NO), inducible nitric oxide synthase (iNOS), and cytokines (TNF-{alpha} and IL-6) in a concentration-dependent manner. Additionally, HBP inhibited the LPS-induced upregulation of cytokines, including TNF-{alpha} and IL-6, and decreased the interstitial infiltration of polymorphonuclear leukocytes in a lung inflammation model. HBP inhibited NF-{kappa}B-dependent inflammatory responses by directly blocking the phosphorylation and degradation of I{kappa}B{alpha} and by subsequently inhibiting the nuclear translocation of the p65 subunit of NF-{kappa}B. Taken together, this novel HBP may be potentially useful candidate for anti-inflammatory treatments and can be combined with other drugs of interest to transport attached molecules into cells.

  11. Influence of HbA1c levels on platelet function profiles associated with tight glycemic control in patients presenting with hyperglycemia and an acute coronary syndrome. A subanalysis of the CHIPS Study ("Control de HIperglucemia y Actividad Plaquetaria en Pacientes con Síndrome Coronario Agudo").

    PubMed

    Vivas, David; García-Rubira, Juan C; Bernardo, Esther; Angiolillo, Dominick J; Martín, Patricia; Calle-Pascual, Alfonso; Núñez-Gil, Iván; Macaya, Carlos; Fernández-Ortiz, Antonio

    2013-02-01

    Patients with hyperglycemia, an acute coronary syndrome and poor glycemic control have increased platelet reactivity and poor prognosis. However, it is unclear the influence of a tight glycemic control on platelet reactivity in these patients. This is a subanalysis of the CHIPS study. This trial randomized patients with hyperglycemia to undergo an intensive glucose control (target blood glucose 80-120 mg/dL), or conventional glucose control (target blood glucose <180 mg/dL). We analyzed platelet function at discharge on the subgroup of patients with poor glycemic control, defined with admission levels of HbA1c higher than 6.5%. The primary endpoint was maximal platelet aggregation following stimuli with 20 μM ADP. We also measured aggregation following collagen, epinephrine, and thrombin receptor-activated peptide, as well as P2Y12 reactivity index and surface expression of glycoprotein IIb/IIIa and P-selectin. A total of 67 patients presented HbA1c ≥ 6.5% (37 intensive, 30 conventional), while 42 had HbA1c < 6.5% (20 intensive, 22 conventional). There were no differences in baseline characteristics between groups. At discharge, patients with HbA1c ≥6.5% had significantly reduced MPA with intensive glucose control compared with conventional control (46.1 ± 22.3 vs. 60.4 ± 20.0%; p = 0.004). Similar findings were shown with other measures of platelet function. However, glucose control strategy did not affect platelet function parameters in patients with HbA1c < 6.5%. Intensive glucose control in patients presenting with an acute coronary syndrome and hyperglycemia results in a reduction of platelet reactivity only in the presence of elevated HbA1c levels.

  12. Crystal structure of a hypothetical protein, TTHA0829 from Thermus thermophilus HB8, composed of cystathionine-β-synthase (CBS) and aspartate-kinase chorismate-mutase tyrA (ACT) domains.

    PubMed

    Nakabayashi, Makoto; Shibata, Naoki; Ishido-Nakai, Emi; Kanagawa, Mayumi; Iio, Yota; Komori, Hirofumi; Ueda, Yasufumi; Nakagawa, Noriko; Kuramitsu, Seiki; Higuchi, Yoshiki

    2016-05-01

    TTHA0829 from Thermus thermophilus HB8 has a molecular mass of 22,754 Da and is composed of 210 amino acid residues. The expression of TTHA0829 is remarkably elevated in the latter half of logarithmic growth phase. TTHA0829 can form either a tetrameric or dimeric structure, and main-chain folding provides an N-terminal cystathionine-β-synthase (CBS) domain and a C-terminal aspartate-kinase chorismate-mutase tyrA (ACT) domain. Both CBS and ACT are regulatory domains to which a small ligand molecule can bind. The CBS domain is found in proteins from organisms belonging to all kingdoms and is observed frequently as two or four tandem copies. This domain is considered as a small intracellular module with a regulatory function and is typically found adjacent to the active (or functional) site of several enzymes and integral membrane proteins. The ACT domain comprises four β-strands and two α-helices in a βαββαβ motif typical of intracellular small molecule binding domains that help control metabolism, solute transport and signal transduction. We discuss the possible role of TTHA0829 based on its structure and expression pattern. The results imply that TTHA0829 acts as a cell-stress sensor or a metabolite acceptor.

  13. Verbascoside is not genotoxic in the ST and HB crosses of the Drosophila wing spot test, and its constituent, caffeic acid, decreases the spontaneous mutation rate in the ST cross.

    PubMed

    Santos-Cruz, Luis Felipe; Ávila-Acevedo, José Guillermo; Ortega-Capitaine, Diego; Ojeda-Duplancher, Jesús Clemente; Perdigón-Moya, Juana Laura; Hernández-Portilla, Luis Barbo; López-Dionicio, Héctor; Durán-Díaz, Angel; Dueñas-García, Irma Elena; Castañeda-Partida, Laura; García-Bores, Ana María; Heres-Pulido, María Eugenia

    2012-03-01

    Verbascoside (VB) is a phenylpropanoid isolated from Buddleja species, some of which originate in Mexico, and was first described in the sixteenth century in the codices of Mexican traditional medicine. VB is present in alcohol extracts and is widely used in the north of Mexico as a sunscreen. VB absorbs UV-A and UV-B radiation and has high antioxidant and anti-inflammatory capacities. VB and its constituent caffeic acid (CA) were screened to determine their genotoxic activity using the Drosophila wing spot test. Third instar larvae (72±4 h) of the standard (ST) and high bioactivation (HB) crosses, with regulated and high levels of cytochrome P450s (Cyp450s), respectively, were exposed to VB or CA (0, 27, 57, 81, 135, and 173 mM). VB was not genotoxic at any of the concentrations tested in both crosses. The amount of VB residue as determined by HPLC in the adult flies that were fed with VB indicated a low metabolism of this compound, which explains the absence of genotoxicity. CA decreased the spontaneous frequencies of small and total spots and showed putative toxicity in the ST cross.

  14. The Ages of 55 Globular Clusters as Determined Using an Improved \\Delta V^HB_TO Method along with Color-Magnitude Diagram Constraints, and Their Implications for Broader Issues

    NASA Astrophysics Data System (ADS)

    VandenBerg, Don A.; Brogaard, K.; Leaman, R.; Casagrande, L.

    2013-10-01

    Ages have been derived for 55 globular clusters (GCs) for which Hubble Space Telescope Advanced Camera for Surveys photometry is publicly available. For most of them, the assumed distances are based on fits of theoretical zero-age horizontal-branch (ZAHB) loci to the lower bound of the observed distributions of HB stars, assuming reddenings from empirical dust maps and metallicities from the latest spectroscopic analyses. The age of the isochrone that provides the best fit to the stars in the vicinity of the turnoff (TO) is taken to be the best estimate of the cluster age. The morphology of isochrones between the TO and the beginning part of the subgiant branch (SGB) is shown to be nearly independent of age and chemical abundances. For well-defined color-magnitude diagrams (CMDs), the error bar arising just from the "fitting" of ZAHBs and isochrones is ≈ ± 0.25 Gyr, while that associated with distance and chemical abundance uncertainties is ~ ± 1.5-2 Gyr. The oldest GCs in our sample are predicted to have ages of ≈13.0 Gyr (subject to the aforementioned uncertainties). However, the main focus of this investigation is on relative GC ages. In conflict with recent findings based on the relative main-sequence fitting method, which have been studied in some detail and reconciled with our results, ages are found to vary from mean values of ≈12.5 Gyr at [Fe/H] <~ - 1.7 to ≈11 Gyr at [Fe/H] >~ -1. At intermediate metallicities, the age-metallicity relation (AMR) appears to be bifurcated: one branch apparently contains clusters with disk-like kinematics, whereas the other branch, which is displaced to lower [Fe/H] values by ≈0.6 dex at a fixed age, is populated by clusters with halo-type orbits. The dispersion in age about each component of the AMR is ~ ± 0.5 Gyr. There is no apparent dependence of age on Galactocentric distance (R G) nor is there a clear correlation of HB type with age. As previously discovered in the case of M3 and M13, subtle variations have

  15. Simultaneous expression of abiotic stress responsive transcription factors, AtDREB2A, AtHB7 and AtABF3 improves salinity and drought tolerance in peanut (Arachis hypogaea L.).

    PubMed

    Pruthvi, Vittal; Narasimhan, Rama; Nataraja, Karaba N

    2014-01-01

    Drought, salinity and extreme temperatures are the most common abiotic stresses, adversely affecting plant growth and productivity. Exposure of plants to stress activates stress signalling pathways that induce biochemical and physiological changes essential for stress acclimation. Stress tolerance is governed by multiple traits, and importance of a few traits in imparting tolerance has been demonstrated. Under drought, traits linked to water mining and water conservation, water use efficiency and cellular tolerance (CT) to desiccation are considered to be relevant. In this study, an attempt has been made to improve CT in drought hardy crop, peanut (Arachis hypogaea L., cv. TMV2) by co-expressing stress-responsive transcription factors (TFs), AtDREB2A, AtHB7 and AtABF3, associated with downstream gene expression. Transgenic plants simultaneously expressing these TFs showed increased tolerance to drought, salinity and oxidative stresses compared to wild type, with an increase in total plant biomass. The transgenic plants exhibited improved membrane and chlorophyll stability due to enhanced reactive oxygen species scavenging and osmotic adjustment by proline synthesis under stress. The improvement in stress tolerance in transgenic lines were associated with induced expression of various CT related genes like AhGlutaredoxin, AhAldehyde reductase, AhSerine threonine kinase like protein, AhRbx1, AhProline amino peptidase, AhHSP70, AhDIP and AhLea4. Taken together the results indicate that co-expression of stress responsive TFs can activate multiple CT pathways, and this strategy can be employed to improve abiotic stress tolerance in crop plants.

  16. Hb Midnapore [β53(D4)Ala→Val; HBB: c.161C>T]: A Novel Hemoglobin Variant with a Structural Abnormality Associated with IVS-I-5 (G>C) (HBB: c.92+5G>C) Found in a Bengali Indian Family.

    PubMed

    Panja, Amrita; Chowdhury, Prosanto; Basu, Anupam

    2016-09-01

    We describe a novel C>T substitution at codon 53 of the HBB gene (HBB: c.161C>T). The proband was a transfusion-dependent β-thalassemia major (β-TM) patient. DNA was extracted and subsequently, DNA sequencing was done to detect the mutations on the HBB gene. Capillary zone electrophoresis (CZE) revealed the presence of an unknown peak. She inherited this mutation from her grandmother through her mother. This mutation exists in cis with the common β(0) mutation IVS-I-5 (G>C) (HBB: c.92+5G>C). The proband is homozygous for HBB: c.92+5G>C and needs monthly transfusions. On the other hand, her grandmother, mother and sister all possess this novel mutation cis with the heterozygous HBB: c.92+5G>C. They are carriers not thalassemic. This mutation produces the substitution β53(D4)Ala→Val; HBB: c.161C>T, a new structural hemoglobin (Hb) variant. As this variant was identified in a Bengali family from Paschim Midnapore district of West Bengal, India, it has been designated as Hb Midnapore. This variant has now been reported to the HbVar database.

  17. Rapid and sensitive anthrone-sulfuric acid assay in microplate format to quantify carbohydrate in biopharmaceutical products: method development and validation.

    PubMed

    Leyva, Alberto; Quintana, Anelis; Sánchez, Meily; Rodríguez, Elias N; Cremata, José; Sánchez, Julio C

    2008-03-01

    The need for an accurate, fast and reliable analysis of carbohydrate test is crucial for numerous biological processes. In that sense, anthrone-sulfuric acid assay is one of the most efficient quantification techniques successfully applied to carbohydrate determination. In this paper, a sensitive and accurate anthrone-sulfuric acid microplate assay was developed and validated for the quantitative estimation of yeast carbohydrates in the production of hepatitis B virus surface antigen, and the main component of the recombinant vaccine HEBERBIOVAC HB. A response surface methodology was applied to design and optimize the assay in order to maximize the differences on the expected effect and to minimize the number of experiments. The proposed method was linear over the concentration range from 10 to 120 microg/mL for glucose, with values for the coefficient of determination >0.99. Intra- and inter-assay variation coefficient ranged between 0.45-4.79% and 2.48-8.94%, respectively. The Student t-test used in the interference study, revealed good parallelism among curves (T(obs)< or =T(0.05)), which indicates the lack of interference in the working range. Yields obtained in accuracy test for two concentration levels varied between 90 and 105%, confirming the assay's reliability. In conclusion, the validated method, which has successfully been used for the process control monitoring of several samples generated from the production of hepatitis B vaccine, allows the quality and purity of the final product.

  18. Role of G protein-coupled receptors (GPCR), matrix metalloproteinases 2 and 9 (MMP2 and MMP9), heparin-binding epidermal growth factor-like growth factor (hbEGF), epidermal growth factor receptor (EGFR), erbB2, and insulin-like growth factor 1 receptor (IGF-1R) in trenbolone acetate-stimulated bovine satellite cell proliferation.

    PubMed

    Thornton, K J; Kamange-Sollo, E; White, M E; Dayton, W R

    2015-09-01

    Implanting cattle with steroids significantly enhances feed efficiency, rate of gain, and muscle growth. However, the mechanisms responsible for these improvements in muscle growth have not been fully elucidated. Trenbolone acetate (TBA), a testosterone analog, has been shown to increase proliferation rate in bovine satellite cell (BSC) cultures. The classical genomic actions of testosterone have been well characterized; however, our results indicate that TBA may also initiate a quicker, nongenomic response that involves activation of G protein-coupled receptors (GPCR) resulting in activation of matrix metalloproteinases 2 and 9 (MMP2 and MMP9) that release membrane-bound heparin-binding epidermal growth factor-like growth factor (hbEGF), which then binds to and activates the epidermal growth factor receptor (EGFR) and/or erbB2. Furthermore, the EGFR has been shown to regulate expression of the IGF-1 receptor (IGF-1R), which is well known for its role in modulating muscle growth. To determine whether this nongenomic pathway is potentially involved in TBA-stimulated BSC proliferation, we analyzed the effects of treating BSC with guanosine 5'-O-2-thiodiphosphate (GDPβS), an inhibitor of all GPCR; a MMP2 and MMP9 inhibitor (MMPI); CRM19, a specific inhibitor of hbEGF; AG1478, a specific EGFR tyrosine kinase inhibitor; AG879, a specific erbB2 kinase inhibitor; and AG1024, an IGF-1R tyrosine kinase inhibitor on TBA-stimulated proliferation rate (H-thymidine incorporation). Assays were replicated at least 9 times for each inhibitor experiment using BSC cultures obtained from at least 3 different animals. Bovine satellite cell cultures were obtained from yearling steers that had no previous exposure to androgenic or estrogenic compounds. As expected, BSC cultures treated with 10 n TBA showed ( < 0.05) increased proliferation rate when compared with control cultures. Additionally, treatment with 5 ng hbEGF/mL stimulated proliferation in BSC cultures ( < 0.05). Treatment

  19. Reliability of isoelectrofocusing for the detection of Hb S, Hb C, and HB D in a pioneering population-based program of newborn screening in Brazil.

    PubMed

    Paixão, M C; Cunha Ferraz, M H; Januário, J N; Viana, M B; Lima, J M

    2001-08-01

    Out of 128,326 newborns in the first 6-month period of a population-based screening program in Minas Gerais, Brazil, a second sample was obtained at the age of 6 months from 4,635 carriers of Hbs AS, AC, and AD which were detected by isoelectrofocusing. Discordance in results occurred in only 27 cases (0.6%): in seven there was a history of hemotransfusion; errors during pipetting or transcription of results occurred in seven cases; it was difficult to differenciate between Hbs S and D in eight patients; and the causes were not elucidated in five patients. The incidence of Hbs FS and FSC for the total population was 1:2,800 and 1:3,450, respectively. Isoelectrofocusing is a very reliable method for distinguishing AS, AC, or AD carriers from patients presenting with [corrected] variant hemoglobin and beta(+)-thalassemia combinations, and may be widely used in massive newborn screening programs.

  20. Optimal haematocrit in subjects with normal haemoglobin genotype (HbAA), sickle cell trait (HbAS), and homozygous sickle cell disease (HbSS).

    PubMed

    Bowers, A S; Pepple, D J; Reid, H L

    2011-01-01

    The determination of an optimal haematocrit (H0) has important clinical implications if such a level can be attained, and more importantly, maintained. This is defined as a haematocrit level, above or below which oxygen delivery is deleteriously affected. This study is designed to determine an optimal haematocrit in normal (AA), sickle cell trait (AS) and sickle cell disease (SS) subjects. Twenty-seven apparently healthy subjects having normal haemoglobin genotype, 24 with sickle cell trait and 42 with homozygous sickle cell disease were recruited into the study. Whole blood viscosity (WBV) was measured by a Wells Brookfield Cone and Plate Viscometer at a shear rate of 230 sec-1. Haematocrit was determined by an AC.Tron Coulter Counter. The optimal haematocrit was calculated as the inverse of a constant, K, which was derived from the haematocrit and viscosity data. Our findings showed that the H0 varied significantly among the 3 haemoglobin genotypes, in the order AA vs SS and AS vs SS. Additionally, the data indicated an increased H0 in subjects with sickle cell trait, suggesting a possible impairment in oxygen delivery in these individuals.

  1. The Composition of HB Stars: RR Lyrae Variables

    NASA Astrophysics Data System (ADS)

    Clementini, G.; Carretta, E.; Gratton, R.; Merighi, R.; Mould, J. R.; McCarthy, J. K.

    1995-11-01

    We used moderately high-resolution, high S/N spectra to study the chemical composition of 10 field ab-type RR Lyrae stars. A new temperature scale was determined from literature Infrared Flux Method measures of subdwarfs and the Kurucz (1992) model atmospheres, and used to calibrate colors for both dwarfs and RR Lyraes. The applicability of Kurucz (1992) model atmospheres in the analysis of RR Lyraes at minimum light was analyzed: we found that they are able to reproduce colors, excitation and ionization equilibria as well as the wings of Halpha. We derived abundances for 21 species. The metal abundances of the program stars span the range -2.50<[Fe/H]<+0.17$. Lines of most elements are found to form in LTE conditions. Fe lines satisfy very well the excitation and ionization equilibria. RR Lyraes share the typical abundance pattern of other stars of similar [Fe/H]: alpha-elements are overabundant by about 0.4dex and Mn is underabundant by about 0.6dex in stars with [Fe/H]<-1. Significant departures from LTE are found only for a few species. We used our new [Fe/H] abundances, as well as values from Butler and coworkers (corrected to our system), and from high resolution spectroscopy of globular clusters giants, to obtain a new calibration of the DeltaS index: [Fe/H]= -0.194(\\pm 0.011)DeltaS -0.08(\\pm 0.18) and to update the metallicity calibration of the Ca II K line index: [Fe/H]= 0.65(\\pm 0.17)W'(K) -3.49(\\pm 0.39). Finally, our new metallicity scale was used to revise the [Fe/H] dependence of the absolute magnitude of RR Lyrae stars, Mv: Mv = 0.20(\\pm 0.03)[Fe/H] + 1.06(\\pm 0.04).

  2. Prototype of the side-hole HB optical fiber

    NASA Astrophysics Data System (ADS)

    Wojcik, Jan; Urbanczyk, Waclaw; Bock, Wojtek J.; Janoszczyk, Barbara; Mergo, Pawel; Makara, Mariusz; Poturaj, Krzysztof; Spytek, Witold

    1999-05-01

    A standard polarization maintaining optical fiber (SMPM- single mode polarization maintain) has either an elliptical core or/and an elliptical inner cladding (bow-tie, panda). These kind of fibers usually display low or modest sensitivity to pressure and high sensitivity to temperature. The side-hole optical fibers having two hollow spaces symmetrically placed on both sides of the core are characterized by much higher sensitivity to pressure. This paper presents results of investigations on sensitivity to pressure and on sensitivity to temperature, which can attain the values of 140 rad/MPa*m and 1 rad/K*m, respectively.

  3. H.B. Robinson-2 pressure vessel benchmark

    SciTech Connect

    Remec, I.; Kam, F.B.K.

    1998-02-01

    The H. B. Robinson Unit 2 Pressure Vessel Benchmark (HBR-2 benchmark) is described and analyzed in this report. Analysis of the HBR-2 benchmark can be used as partial fulfillment of the requirements for the qualification of the methodology for calculating neutron fluence in pressure vessels, as required by the U.S. Nuclear Regulatory Commission Regulatory Guide DG-1053, Calculational and Dosimetry Methods for Determining Pressure Vessel Neutron Fluence. Section 1 of this report describes the HBR-2 benchmark and provides all the dimensions, material compositions, and neutron source data necessary for the analysis. The measured quantities, to be compared with the calculated values, are the specific activities at the end of fuel cycle 9. The characteristic feature of the HBR-2 benchmark is that it provides measurements on both sides of the pressure vessel: in the surveillance capsule attached to the thermal shield and in the reactor cavity. In section 2, the analysis of the HBR-2 benchmark is described. Calculations with the computer code DORT, based on the discrete-ordinates method, were performed with three multigroup libraries based on ENDF/B-VI: BUGLE-93, SAILOR-95 and BUGLE-96. The average ratio of the calculated-to-measured specific activities (C/M) for the six dosimeters in the surveillance capsule was 0.90 {+-} 0.04 for all three libraries. The average C/Ms for the cavity dosimeters (without neptunium dosimeter) were 0.89 {+-} 0.10, 0.91 {+-} 0.10, and 0.90 {+-} 0.09 for the BUGLE-93, SAILOR-95 and BUGLE-96 libraries, respectively. It is expected that the agreement of the calculations with the measurements, similar to the agreement obtained in this research, should typically be observed when the discrete-ordinates method and ENDF/B-VI libraries are used for the HBR-2 benchmark analysis.

  4. Spectrophotometers for plutonium monitoring in HB-line

    SciTech Connect

    Lascola, R. J.; O'Rourke, P. E.; Kyser, E. A.; Immel, D. M.; Plummer, J. R.; Evans, E. V.

    2016-02-12

    This report describes the equipment, control software, calibrations for total plutonium and plutonium oxidation state, and qualification studies for the instrument. It also provides a detailed description of the uncertainty analysis, which includes source terms associated with plutonium calibration standards, instrument drift, and inter-instrument variability. Also included are work instructions for instrument, flow cell, and optical fiber setup, work instructions for routine maintenance, and drawings and schematic diagrams.

  5. Glomerular filtration rate is altered in children with sickle cell disease: a comparison between Hb SS and Hb SC

    PubMed Central

    de Paula, Rafael Pereira; Nascimento, Alana Ferreira; Sousa, Sandra Mara Bispo; Bastos, Paulo Roberto Velasco; Barbosa, Ana Angélica Leal

    2013-01-01

    Background Renal failure is common among older patients with sickle cell disease; this is preceded by subclinical glomerular hyperfiltration. Data about renal function of adults with sickle cell disease have been reported, but data on children is scarce, especially when comparing heterozygotic and homozygotic patients. Objective The goal of this study was to investigate the glomerular filtration rate of heterozygotic and homozygotic children with sickle cell disease. Methods The glomerular filtration rate of 11 children with sickle cell disease [7 homozygotic (SS) and 4 heterozygotic (SC)] with a mean age of 11 years (standard deviation: ± 5 years) was evaluated using standard laboratory techniques. Results are presented as descriptive analysis. Results Our results suggest that glomerular hyperfiltration is present in children with sickle cell disease; this is more evident in homozygotic than heterozygotic children. Conclusion There is evidence of a need to monitor the renal function of children with sickle cell disease when special attention should be paid to homozygotic patients. PMID:24255619

  6. Evidence for the h_b(1P) meson in the decay Upsilon(3S) --> pi0 h_b(1P)

    SciTech Connect

    Lees, J.P.

    2011-08-12

    Using a sample of 122 million {Upsilon}(3S) events recorded with the BABAR detector at the PEP-II asymmetric-energy e{sup +}e{sup -} collider at SLAC, we search for the h{sub b}(1P) spin-singlet partner of the P-wave {chi}{sub b}(1P) states in the sequential decay {Upsilon}(3S) {yields} {pi}{sup 0}h{sub b}(1P), h{sub b}(1P) {yields} {gamma}{eta}{sub b}(1S). We observe an excess of events above background in the distribution of the recoil mass against the {pi}{sup 0} at mass 9902 {+-} 4(stat.) {+-} 1(syst.) MeV/c{sup 2}. The width of the observed signal is consistent with experimental resolution, and its significance is 3.0 {sigma}, including systematic uncertainties. We obtain the value (3.7 {+-} 1.1 (stat.) {+-} 0.7 (syst.)) x 10{sup -4} for the product branching fraction {Beta}({Upsilon}(3S) {yields} {pi}{sup 0}h{sub b}) x {Beta}(h{sub b} {yields} {gamma}{eta}{sub b}).

  7. Managing type 2 diabetes: balancing HbA1c and body weight.

    PubMed

    Mavian, Annie A; Miller, Stephan; Henry, Robert R

    2010-05-01

    Most patients with type 2 diabetes present with comorbid overweight or obesity. Reaching and maintaining acceptable glycemic control is more difficult in overweight and obese patients, and these conditions are associated with increased risk for cardiovascular and other diseases. Glycemic management for these patients is complicated by the fact that insulin and many of the oral medications available to treat type 2 diabetes produce additional weight gain. However, an increasing number of therapeutic options are available that are weight neutral or lead to weight loss in addition to their glycemic benefits. This article evaluates the evidence from clinical trials regarding the relative glycemic benefits, measured in terms of glycated hemoglobin change, versus the impact on body weight of each medication currently approved for type 2 diabetes. In general, the sulfonylureas, thiazolidinediones, and D-phenylalanine derivatives have been shown to promote weight gain. The dipeptidyl peptidase-4 inhibitors are weight neutral, while the biguanides, incretin mimetics, and amylin mimetics promote weight loss. Trials examining the glycemic benefits of the weight loss agents orlistat and sibutramine are also examined. Awareness of this evidence base can be used to inform medication selection in support of weight management goals for patients with type 2 diabetes.

  8. 26 CFR 54.4980H-5 - Assessable payments under section 4980H(b).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... dependents minimum essential coverage that provides minim