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Sample records for recombinante heberbiovac hb

  1. Hb Cervantes, Hb Marañón, Hb La Mancha and Hb Goya: Description of 4 new haemoglobinopathies.

    PubMed

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

    2015-07-01

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

  2. Baseline Report on HB2320

    ERIC Educational Resources Information Center

    State Council of Higher Education for Virginia, 2015

    2015-01-01

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

  3. Hepatitis B (HB) immunoglobulin plus HB vaccine for intrauterine HB virus infection.

    PubMed

    Iwasawa, Kentaro; Inui, Ayano; Tsunoda, Tomoyuki; Kondo, Takeo; Kawamoto, Manari; Sogo, Tsuyoshi; Komatsu, Haruki; Fujisawa, Tomoo

    2015-06-01

    Vaccination against hepatitis B virus (HBV) infection in infants born to hepatitis B surface antigen (HBsAg)-positive mothers using HB immunoglobulin (HBIG) and hepatitis B (HB) vaccine was launched in Japan in 1985. Infants testing positive for HBsAg at 1 month of age are considered to have prenatally acquired the infection and are usually excluded from the prevention program. Infants born to HB e antigen (HBeAg)-positive mothers are at a high risk of perinatally acquiring the infection. In this study, long-term outcome was evaluated in children with prenatal HBV infection who received the HBIG and HB vaccine in Japan. Newborns of both HBsAg- and HBeAg-positive carrier mothers received HBIG within 48 h of birth and at 2 months of age. Subsequently, three doses of recombinant HB vaccine were given at 2, 3, and 5 months of age. Outcome was compared between the following two groups: infants who completed the vaccination program, even if they were HBsAg positive at 1 month of age (n = 15), and infants who did not (n = 51). Seroconversion from HBeAg to anti-HBe antibody (HBeAb) before 3 years of age was observed in five children (33%) who completed the vaccination program and in two (4%) who did not (P = 0.005). In 2/5 children who completed the vaccination program and achieved HBeAb seroconversion, seroconversion from HBsAg to anti-HBs antibody was also noted. This specific vaccination program for children with prenatal HBV infection has the potential to alter immune tolerance to HBV. © 2014 Japan Pediatric Society.

  4. Biodegradation of P(3HB-co-4HB) powder by Pseudomonas mendocina for preparation low-molecular-mass P(3HB-co-4HB).

    PubMed

    Gao, Zhaoying; Su, Tingting; Li, Ping; Wang, Zhanyong

    2017-10-01

    Poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P(3HB-co-4HB)) is a biodegradable plastic that is extensively utilized in many fields. In this work, P(3HB-co-4HB) powder was degraded by Pseudomonas mendocina for the preparation of low-molecular-mass (LMW) P(3HB-co-4HB). After degradation, the remaining P(3HB-co-4HB) powder was analyzed via gel permeation chromatography (GPC), differential scanning calorimetry (DSC), X-ray powder diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, and proton nuclear magnetic resonance ((1)H NMR) spectroscopy. The degradation of P(3HB-co-4HB) by P. mendocina occurred in two stages: the fast degradation stage (0-8 h) and the slow degradation stage (8-24 h). GPC analysis showed that the molecular weight of P(3HB-co-4HB) gradually decreased with degradation time. After 24 h of degradation, the weight-average molecular weight of P(3HB-co-4HB) was reduced to 4-5 kDa. DSC and XRD analyses both verified that the degree of crystallinity decreased with prolonged degradation time. The melting temperature of the degraded powder, however, remained unchanged. FTIR and (1)H NMR analyses of the degraded powder showed that no new material was produced during degradation. Thus, the degradation of P(3HB-co-4HB) by P. mendocina could be used to produce LMW P(3HB-co-4HB) for use in various applications, such as the synthesis of amphiphilic block copolymers.

  5. HbD Punjab/HbQ India Compound Heterozygosity: An Unusual Association

    PubMed Central

    Colaco, Stacy; Surve, Reema; Sawant, Pratibha; Nadkarni, Anita; Ghosh, Kanjaksha; Colah, Roshan

    2014-01-01

    Background Haemoglobinopathies are the commonest hereditary disorders in India and pose a major health problem. Both beta thalassaemia and structural haemoglobin variants are relatively common in northwestern India. Here we report a 29-year-old Sindhi female who was referred to us for a haemoglobinopathy work up and genetic counseling since her spouse was a classical beta thalassaemia carrier. Method A complete blood count was done on an automated cell counter. Haemoglobin analysis was carried out using HPLC Variant Haemoglobin Testing System. The cellulose acetate electrophoresis was carried out [pH 8.9]. Confirmation of mutations was done by automated DNA sequencing. Results HPLC analysis showed four major peaks, HbA0, a peak in the HbD window, an unknown peak [retention time 4.74 minutes] and a peak in the HbC window. The HbA2 level was 2.2%, and the HbF level was 0.7%. Cellulose acetate electrophoresis at alkaline pH, a slow moving band was seen at the HbS/D position along with a prominent band at the HbA2 position. DNA sequencing of the β and α genes showed presence of the two hemoglobin variants: Hb D [β 121GAA → CAA] and Hb Q [α 64 AAG → GAG]. The δ globin gene was normal. The additional peak in the HbC window was due to the formation of a heterodimer hybrid. Conclusion Both HbD Punjab and HbQ India are relatively common in India, but their co-inheritance has not been described in the country. This case is the third report of compound heterozygosity for HbQ India/HbD Punjab haemoglobinopathy globally and the second one from India. PMID:25408858

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

    PubMed

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

    2016-12-01

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

  7. 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

  8. 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.

  9. Effects of hemoglobin variants HbJ Bangkok, HbE, HbG Taipei, and HbH on analysis of glycated hemoglobin via ion-exchange high-performance liquid chromatography.

    PubMed

    Zhang, Xiu-Ming; Wen, Dong-Mei; Xu, Sheng-Nan; Suo, Ming-Huan; Chen, Ya-Qiong

    2017-04-13

    To explore the effects of HbJ Bangkok, HbE, HbG Taipei, and α-thalassemia HbH on the results of HbA1c assessment using ion-exchange high-performance liquid chromatography (IE-HPLC). We enrolled five patients in which the results of the IE-HPLC HbA1c assay were inconsistent with the average levels of FBG. We performed hemoglobin capillary (Hb) electrophoresis using whole-blood samples. We also sequenced the genes encoding Hb using dideoxy-mediated chain termination and analyzed HbA1c using borate affinity HPLC (BA-HPLC) and turbidimetric inhibition immunoassay (TINIA). Two patients had the HbJ Bangkok variant. Hb genotypes of these patients were β(41-42) /β(J Bangkok) and β(N) /β(J Bangkok) , and the content of HbJ Bangkok was 93.9% and 52.4%, respectively. The remaining three patients had the following: HbE (β(N) /β(E) Hb genotype, 23.6% HbE content), HbG Taipei (β(N) /β(G Taipei) Hb genotype, 39.4% HbG Taipei content), and α-thalassemia HbH (6.1% HbH content, 2.8% Hb Bart's content). In the patients with β-thalassemia and HbJ Bangkok variants, the presence of the variants interfered with the results of HbA1c analyses using IE-HPLC and TINIA; in the remaining four patients, there was interference with the results of HbA1c IE-HPLC but not with the TINIA assay. There was no interference with BA-HPLC HbA1c results. HbJ Bangkok, HbE, HbG Taipei Hb, and α-thalassemia HbH disease cause varying degrees of interference with the analysis of HbA1c using IE-HPLC. In these patients, we suggest using methods free from such interference for the analysis of HbA1c and other indicators to monitor blood glucose levels. © 2017 Wiley Periodicals, Inc.

  10. 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.

  11. 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.

  12. Co-inheritance of α(0) -thalassemia elevates Hb A2 level in homozygous Hb E: Diagnostic implications.

    PubMed

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

    2017-10-01

    Differentiation of homozygous hemoglobin (Hb) E with and without α(0) -thalassemia is subtle on routine hematological ground. We examined in a large cohort of homozygous Hb E if the level of Hb A2 is helpful. A total of 592 subjects with homozygous Hb E were recruited from ongoing thalassemia screening program. Additionally, five couples at risk of having fetuses with Hb Bart's hydrops fetalis who were homozygous Hb E were also investigated. Hb analysis was performed using capillary electrophoresis system. Globin genotypes were defined by DNA analysis. Subjects were classified into four groups including pure homozygous Hb E (n=532), homozygous Hb E/α(0) -thalassemia (n=48), Hb Constant Spring EE Bart's disease (n=8), and Hb EE Bart's disease (n=4). The levels of Hb A2 were found, respectively, to be 4.97±0.69, 6.64±1.02, 4.86±0.87, and 7.60±1.04%. Among five couples at risk, α(0) -thalassemia was identified in three subjects with Hb A2 >6.0%. Increased Hb A2 level is a useful marker for differentiation of homozygous Hb E with and without α(0) -thalassemia. This should lead to a significant reduction in number of referral cases of homozygous Hb E for molecular testing of α(0) -thalassemia in routine practice. © 2017 John Wiley & Sons Ltd.

  13. Multicentre evaluation of the Premier Hb9210 HbA1c analyser

    PubMed Central

    John, W. Garry; Little, Randie; Sacks, David B.; Weykamp, Cas; Lenters-Westra, Erna; Hornsby, Theresa; Zhao, Zhen; Siebelder, Carla; Tennill, Alethea; English, Emma

    2017-01-01

    Background The accurate and precise quantification of HbA1c is essential for the diagnosis and routine monitoring of patients with diabetes. We report an evaluation of the Trinity Biotech Premier Hb9210 analyser (Bray, Ireland/Kansas City, US), a boronate affinity chromatography-based high performance liquid chromatography (HPLC) system for the measurement of glycated haemoglobin. Methods We evaluated the analytical performance of the Hb9210 as part of a multicentre evaluation. The effect of haemoglobin variants, other potential interferences and the performance in comparison to both the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) and National Glycohemoglobin Standardization Program (NGSP) reference systems, was assessed. Most of the centres participating also act as reference laboratories for both the IFCC standardisation network for HbA1c and the NGSP. Results The combined data from all centres showed total CVs of 2.71%, 2.32% and 2.14% at low medium and high values respectively for mmol/mol (SI units) and 1.62%, 1.59% and 1.68% for % (NGSP units), which are well below the recommended upper limits of 3% CV for SI (IFCC) units and 2% CV for % (NGSP). The analyser showed a good correlation to HbA1c methods currently used in clinical practice and the IFCC reference method procedure. Haemoglobin variants AC, AS, AE and AD do not affect the measurement of HbA1c. Overall the Hb9210 performs well across the whole analytical range. Conclusions The Hb9210 performs well and is suitable for clinical application in the analysis of HbA1c. PMID:25274956

  14. Catalase against met-Hb excess during oximetries of dilute Hb-A samples.

    PubMed

    Ricco, G; David, O; Lanza, C; Perfetto, F; Rabino-Massa, E

    1996-01-01

    Functional parameters of diluted Hb-A have been determined before and after addition of catalase and disodium-EDTA to the samples. There are no important differences between the results drawn from catalase added samples and catalase free ones, except for the fact the met-Hb level at pH 7.8 is significantly lower in the samples containing catalase. On the contrary, catalase is almost ineffective against met-Hb at pH 6.8, whereas its activity at pH 7.3 is rather modest. Another limitation is that catalase remains active against met-Hb for not more than 15-20 minutes after addition to the sample, which is just the time necessary for one complete (manual) oximetry.

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

    PubMed Central

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

    2015-01-01

    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. PMID:26870793

  16. 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.

  17. 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. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  18. Characterization of HbWRKY1, a WRKY transcription factor from Hevea brasiliensis that negatively regulates HbSRPP.

    PubMed

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

    2013-10-01

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

  19. Differential Thermal Stability and Oxidative Vulnerability of the Hemoglobin Variants, HbA2 and HbE

    PubMed Central

    Chakrabarti, Abhijit; Bhattacharya, Dipankar; Deb, Sanghamitra; Chakraborty, Madhumita

    2013-01-01

    Apart from few early biophysical studies, the relative thermal instability of HbE has been only shown by clinical investigations. We have compared in vitro thermal stability of HbE with HbA2 and HbA using optical spectroscopy. From absorption measurements in the soret region, synchronous fluorescence spectroscopy and dynamic light scattering experiments, we have found thermal stability of the three hemoglobin variants following the order HbEA2 in terms of structural unfolding and aggregation pattern. We have found formation of intermolecular dityrosine fluorophores with characteristic fluorescence signature, at pH >11.0 in all the three variants. Under oxidative stress conditions in presence of hydrogen peroxide, HbE has been found to be more vulnerable to aggregation compared to HbA and HbA2. Taken together, these studies have shown thermal and oxidative instability of HbE and points towards the role of HbE in the upregulation of redox regulators and chaperone proteins in erythrocyte proteome of patients suffering from HbEbeta thalassemia. PMID:24244748

  20. Origin of Hb A2' (Hb B2) [delta16(A13)Gly --> Arg (GGC --> CGC)].

    PubMed

    Bennani, Mohcine; Mombo, Landry-Erik; Chaventre, André; Barakat, Amina; Ducrocq, Rolande; Nagel, Ronald L; Krishnamoorthy, Rajagopal

    2003-05-01

    On a field trip to the Dogon country (le Pays Dogon) in central Mali, we detected a high frequency of the Hb A2 abnormality, reaching higher numbers among blacksmiths (up to 12.4%) living in the same villages. In this report, by direct nucleotide sequencing and employing a polymerase chain reaction-restriction fragment length polymorphism approach, we show that the Hb A2 variant observed in the Dogon population is indeed Hb A2', also called Hb B2, and that in all of the cases the abnormal delta-globin gene is linked to a unique haplotype. The same haplotype was found linked to Hb A2' in the Herero population belonging to the South African Bantu-speaking Blacks from Namibia. Although the unique origin of this mutation in Africa is a possibility, a recurrent mutational event cannot be excluded because the linked beta cluster haplotype is one of the two major haplotypes found in all African populations. A study of populations from other regions of Africa is required to clarify this issue.

  1. Estimation of the quantum efficiency of the photodissociation of HbO2 and HbCO

    NASA Astrophysics Data System (ADS)

    Gisbrecht, A. I.; Mamilov, S. A.; Esman, S. S.; Asimov, M. M.

    2016-01-01

    The paper presents our results on the study of the efficiency of inter-fractional changes in hemoglobin molecules depending on the laser radiation parameters. The evaluation of the quantum efficiency of light interaction in vivo with oxyhemoglobin (HbO2) and carboxyhemoglobin (HbCO) in the blood at wavelengths for 525 and 605 nm is presented. The photodissociation yield of 11% for HbO2 and 79% for HbCO are measured at the wavelength of 525 nm and 10 % for HbO2 and 76 % for HbCO at a wavelength of 605 nm. Thus, the quantum yield of photodissociation of the HbCO is considerably higher, which ensures high efficiency of photodecomposition of the HbCO in the blood. The obtained results can be used in the clinical phototherapy practice for effective treatment of CO poisoning.

  2. 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.

  3. 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

  4. 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.

  5. [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.

  6. 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.

  7. First Case of a Compound Heterozygosity for Two Nondeletional α-Thalassemia mutations, Hb Constant Spring and Hb Quong Sze.

    PubMed

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

    2016-06-01

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

  8. 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.

  9. Hemoglobin variants detected by hemoglobin A1c (HbA1c) analysis and the effects on HbA1c measurements.

    PubMed

    Nasir, Nadzimah Mohd; Thevarajah, M; Yean, Chew Yee

    2010-04-01

    Hemoglobin (Hb) A1c is a tool widely used to monitor long-term glycemic control in diabetic patients. The objective of our study is to compare the HbA1c values measured on high performance liquid chromatography (HPLC) and immunoassay in patients who were detected to have hemoglobin variant after HbA1c analysis. We compared the HbA1c values measured using the Arkray Adams A1c HA-8160 (HPLC method) and Roche Cobas Integra (immunoturbidimetric method) from diabetic patients who were diagnosed with hemoglobin variants. Forty-three diabetic patients were diagnosed with hemoglobin variants: 13 elevated Hb F, 12 Hb E trait, seven Hb S trait, seven Hb D trait, two Hb E / beta-Thalassemia, one Hb C trait, and one homozygous Hb S. Knowledge of hemoglobin variants affecting HbA1c measurements is essential, in order to avoid mismanagement of diabetic patients.

  10. 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

  11. MP4, a new nonvasoactive PEG-Hb conjugate.

    PubMed

    Vandegriff, Kim D; Malavalli, Ashok; Wooldridge, Jerod; Lohman, Jeff; Winslow, Robert M

    2003-04-01

    Vasoconstriction has been an obstacle to clinical development of Hb-based O2 carriers. It is proposed that this limitation can be overcome by increasing molecular size and oxygen affinity. Surface-modified Hb (MP4) was designed, whose properties are consistent with the theory that cell-free Hb engages autoregulatory vasoconstrictive responses to Hb diffusion in the plasma space ("facilitated diffusion"). Human Hb was modified by reaction first with 2-iminothiolane to add sulfhydryl groups and then with monofunctional maleimide- activated 5-kDa PEG. MP4 was found to have a molecular weight of 90 kDa, a molecular radius increased relative to native Hb (9.3 +/- 1.4 vs. 3.2 nm), high oxygen affinity (p50 approximately 5-6 mmHg), and a Bohr effect approximately half that of native human Hb (-0.24Deltalogp50/DeltapH). At 4.2 g per dL in Ringer's lactate, its viscosity was 2.5 cP, and its oncotic pressure was 50 mmHg. The t50 of 14C-MP4 in rats was approximately 24 hours. No significant elevation in mean arterial pressure was observed. MP4 appears to be free of a pressor effect, a major limitation to the development of a safe and effective RBC substitutes in the past.

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

    PubMed

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

    2015-06-01

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

  13. Comparative haematological parameters of HbAA and HbAS genotype children infected with Plasmodium falciparum malaria in Yemen.

    PubMed

    Albiti, Anisa H; Nsiah, Kwabena

    2014-04-01

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

  14. 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.

  15. 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.

  16. 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.

  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 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

  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 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

  19. 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

  20. 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.

  1. [Homozygous hemoglobin-E (Hb-EE) disease].

    PubMed

    Amendola, G; Danise, P; Di Palma, A; Franzese, M; Avino, D; D'Arco, A M

    2004-01-01

    The Authors report on a 16 year-old girl, of Cambodian descent, who was admitted to the hospital for hematuria. She showed a mild microcytic, hypochromic anemia with a normal iron balance; clinical examination was normal with neither pallor nor icterus nor splenomegaly; electrophoresis of hemoglobin yielded no hemoglobin A, a sligtly increased amount of HbF and a single band with a mobility similar to that of HbA2; the patient showed no evidence of overt increased hemolysis. With the DNA technology a final diagnosis of homozygous hemoglobin E was made. Hemoglobin E is the most common Hb variant among Southeast Asian populations. The Authors discuss on the benign nature of Hb-EE disease, pointing out that the presence of a single HbE gene in combination with that for beta-thalassemia leads generally to a disorder often comparable in severity to that of homozygous beta-thalassemia. With the recent migration of a high number of people from the countries, where HbE is extremely frequent, to the Western world (including Italy), this thalassemia syndrome is now a global health problem; therefore its knowledge is an important diagnostic challenge to all the experts involved in the care of thalassemic patients.

  2. 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.

  3. 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

  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. 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.

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

    PubMed Central

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

    2016-01-01

    Glycated haemoglobin (HbA1c) 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 HbA1c 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 HbA1c. 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 HbA1c 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 HbA1c.
Capillary electrophoresis is a good method for detecting HbJ but does not seem suitable for evaluation of HbA1C value in patients in presence of HbJ variant. PMID:27346969

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

    PubMed

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

    2017-02-01

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

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

    PubMed Central

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

    2017-01-01

    Introduction Thalassemia could interfere with some assays for haemoglobin A1c (HbA1c) measurement, therefore, it is useful to be able to screen for thalassemia while measuring HbA1c. We used Capillarys 2 Flex Piercing (Capillarys 2FP) HbA1c programme to simultaneously measure HbA1c and screen for thalassemia. Materials and methods Samples from 498 normal controls and 175 thalassemia patients were analysed by Capillarys 2FP HbA1c programme (Sebia, France). For method comparison, HbA1c was quantified by Premier Hb9210 (Trinity Biotech, Ireland) in 98 thalassaemia patients samples. For verification, HbA1c from eight thalassaemia patients was confirmed by IFCC reference method. Results Among 98 thalassaemia samples, Capillarys 2FP did not provide an HbA1c result in three samples with HbH due to the overlapping of HbBart’s with HbA1c fraction; for the remaining 95 thalassaemia samples, Bland-Altman plot showed 0.00 ± 0.35% absolute bias between two systems, and a significant positive bias above 7% was observed only in two HbH samples. The HbA1c values obtained by Capillarys 2FP were consistent with the IFCC targets (relative bias below ± 6%) in all of the eight samples tested by both methods. For screening samples with alpha (α-) thalassaemia silent/trait or beta (β-) thalassemia trait, the optimal HbA2 cut-off values were ≤ 2.2% and > 2.8%, respectively. Conclusions Our results demonstrated the Capillarys 2FP HbA1c system could report an accurate HbA1c value in thalassemia silent/trait, and HbA2 value (≤ 2.2% for α-thalassaemia silent/trait and > 2.8% for β-thalassemia trait) and abnormal bands (HbH and/or HbBart’s for HbH disease, HbF for β-thalassemia) may provide valuable information for screening. PMID:28900367

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

    PubMed

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

    2017-10-01

    Thalassemia could interfere with some assays for haemoglobin A1c (HbA1c) measurement, therefore, it is useful to be able to screen for thalassemia while measuring HbA1c. We used Capillarys 2 Flex Piercing (Capillarys 2FP) HbA1c programme to simultaneously measure HbA1c and screen for thalassemia. Samples from 498 normal controls and 175 thalassemia patients were analysed by Capillarys 2FP HbA1c programme (Sebia, France). For method comparison, HbA1c was quantified by Premier Hb9210 (Trinity Biotech, Ireland) in 98 thalassaemia patients samples. For verification, HbA1c from eight thalassaemia patients was confirmed by IFCC reference method. Among 98 thalassaemia samples, Capillarys 2FP did not provide an HbA1c result in three samples with HbH due to the overlapping of HbBart's with HbA1c fraction; for the remaining 95 thalassaemia samples, Bland-Altman plot showed 0.00 ± 0.35% absolute bias between two systems, and a significant positive bias above 7% was observed only in two HbH samples. The HbA1c values obtained by Capillarys 2FP were consistent with the IFCC targets (relative bias below ± 6%) in all of the eight samples tested by both methods. For screening samples with alpha (α-) thalassaemia silent/trait or beta (β-) thalassemia trait, the optimal HbA2 cut-off values were ≤ 2.2% and > 2.8%, respectively. Our results demonstrated the Capillarys 2FP HbA1c system could report an accurate HbA1c value in thalassemia silent/trait, and HbA2 value (≤ 2.2% for α-thalassaemia silent/trait and > 2.8% for β-thalassemia trait) and abnormal bands (HbH and/or HbBart's for HbH disease, HbF for β-thalassemia) may provide valuable information for screening.

  10. Arabidopsis AtHB7 and AtHB12 evolved divergently to fine tune processes associated with growth and responses to water stress.

    PubMed

    Ré, Delfina A; Capella, Matías; Bonaventure, Gustavo; Chan, Raquel L

    2014-05-31

    Arabidopsis AtHB7 and AtHB12 transcription factors (TFs) belong to the homeodomain-leucine zipper subfamily I (HD-Zip I) and present 62% amino acid identity. These TFs have been associated with the control of plant development and abiotic stress responses; however, at present it is not completely understood how AtHB7 and AtHB12 regulate these processes. By using different expression analysis approaches, we found that AtHB12 is expressed at higher levels during early Arabidopsis thaliana development whereas AtHB7 during later developmental stages. Moreover, by analysing gene expression in single and double Arabidopsis mutants and in transgenic plants ectopically expressing these TFs, we discovered a complex mechanism dependent on the plant developmental stage and in which AtHB7 and AtHB12 affect the expression of each other. Phenotypic analysis of transgenic plants revealed that AtHB12 induces root elongation and leaf development in young plants under standard growth conditions, and seed production in water-stressed plants. In contrast, AtHB7 promotes leaf development, chlorophyll levels and photosynthesis and reduces stomatal conductance in mature plants. Moreover AtHB7 delays senescence processes in standard growth conditions. We demonstrate that AtHB7 and AtHB12 have overlapping yet specific roles in several processes related to development and water stress responses. The analysis of mutant and transgenic plants indicated that the expression of AtHB7 and AtHB12 is regulated in a coordinated manner, depending on the plant developmental stage and the environmental conditions. The results suggested that AtHB7 and AtHB12 evolved divergently to fine tune processes associated with development and responses to mild water stress.

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

    PubMed

    Rodriguez-Capote, Karina; Higgins, Trefor N

    2015-07-01

    The aims of this study were to identify the incidence of hemoglobinopathies and thalassemias in Northern Alberta and calculate the reference intervals (RI) for hemoglobin (Hb) HbF and HbA2. A retrospective ad-hoc analysis of the structural Hb variants and thalassemias identified on patients who had a hemoglobinopathy/thalassemia investigation performed between February 1 to December 31, 2013. Results were extracted from the Laboratory Information System. Statistical analysis was performed using MedCalc® version 11.4.2.0 for Windows software. 6616 hemoglobinopathy/thalassemia investigations and HbS screens were physician requested and 602 Hb variants were fortuitously found during HbA1c analysis. 3438 were interpreted as "normal" and 532 were classified as iron deficient. 3306 individuals, with age ranging from 3 to 92 years were included in the RI calculation. HbA2 RI was 2.3% to 3.4% and HbF 0.0% to 1.8%. 524 and 423 α and β thalassemia traits respectively were identified. Additionally ten δβ thalassemia traits and twelve cases of HbH disease were identified. Regarding hemoglobinopathies, 7% were classified as α-chain variants and 93% as β-chain variants with HbS (46%), HbE (16%), HbD Punjab (8%) and HbC (7%) traits being the most prevalent. We also documented 20 homozygous hemoglobinopathies and 36 compound/double heterozygous hemoglobinopathies. A wide diversity of hemoglobinopathies is found in the Northern Alberta population, 80% of the hemoglobinopathies were found as a reflex to HbA1c testing. Reference intervals for HbF and HbA2 were established. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  12. Arabidopsis AtHB7 and AtHB12 evolved divergently to fine tune processes associated with growth and responses to water stress

    PubMed Central

    2014-01-01

    Background Arabidopsis AtHB7 and AtHB12 transcription factors (TFs) belong to the homeodomain-leucine zipper subfamily I (HD-Zip I) and present 62% amino acid identity. These TFs have been associated with the control of plant development and abiotic stress responses; however, at present it is not completely understood how AtHB7 and AtHB12 regulate these processes. Results By using different expression analysis approaches, we found that AtHB12 is expressed at higher levels during early Arabidopsis thaliana development whereas AtHB7 during later developmental stages. Moreover, by analysing gene expression in single and double Arabidopsis mutants and in transgenic plants ectopically expressing these TFs, we discovered a complex mechanism dependent on the plant developmental stage and in which AtHB7 and AtHB12 affect the expression of each other. Phenotypic analysis of transgenic plants revealed that AtHB12 induces root elongation and leaf development in young plants under standard growth conditions, and seed production in water-stressed plants. In contrast, AtHB7 promotes leaf development, chlorophyll levels and photosynthesis and reduces stomatal conductance in mature plants. Moreover AtHB7 delays senescence processes in standard growth conditions. Conclusions We demonstrate that AtHB7 and AtHB12 have overlapping yet specific roles in several processes related to development and water stress responses. The analysis of mutant and transgenic plants indicated that the expression of AtHB7 and AtHB12 is regulated in a coordinated manner, depending on the plant developmental stage and the environmental conditions. The results suggested that AtHB7 and AtHB12 evolved divergently to fine tune processes associated with development and responses to mild water stress. PMID:24884528

  13. Factors affecting the binding of trout HbI and HbIV to washed cod mince model system and their influence on lipid oxidation.

    PubMed

    Sannaveerappa, Thippeswamy; Cai, He; Richards, Mark P; Undeland, Ingrid

    2014-01-15

    Electrostatic interactions between haemoglobin (Hb) and muscle components of fish may be an initial step of Hb-mediated lipid oxidation. This mechanism was investigated by examining the interaction of anionic HbIV and cationic HbI with insoluble components of washed cod mince under different pH and salt conditions. Lipid oxidation was monitored in parallel using the thiobarbituric acid reactive substances (TBARS) test. Higher binding of HbI to washed cod mince occurred compared to HbIV, yet HbIV better promoted lipid oxidation. An increase in pH from 5.7 to 6.3 and further to 7.0 lowered both Hb-binding and TBARS development. Addition of NaCl decreased Hb-binding but still did not influence Hb-mediated lipid oxidation. Thus, Hb binding had no consistent effect on lipid oxidation of washed cod mince. Rapid haemin release from the anionic Hb appeared to be a primary facilitator of lipid oxidation, overshadowing the greater binding ability of the cationic Hb. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. 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.

  15. 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

  16. The History of GalaFLEX P4HB Scaffold.

    PubMed

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

    2016-11-01

    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. © 2016 The American Society for Aesthetic Plastic Surgery, Inc.

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. 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.

  3. Prenatal diagnosis of HbE-Lepore and Hb Lepore-β-thalassemia: the importance of accurate genotyping of the couple at risk.

    PubMed

    Italia, Khushnooma; Sheth, Jayesh; Sawant, Pratibha; Nadkarni, Anita; Ghosh, Kanjaksha; Colah, Roshan

    2012-07-01

    To accurately define unusual genotypes in compound heterozygotes for hemoglobinopathies before undergoing prenatal diagnosis. The HPLC results showed one of the parents in case A and B and a child in case C to be HbE-beta-thalassemia. However, this finding did not correlate with molecular findings. Further screening of their grandparents and analysis of DNA for HbLepore were performed. The presence of a typical hump in the peak in the HbA(2) window (10-15%) in one of the grandparents led to the suspicion of a large deletion. Further molecular screening for HbLepore concluded that case A was compound heterozygous for HbLepore-Hollandia-(δ22/β50) and HbE, case B for HbLepore-Boston-Washington-(δ287/β116) and IVS-I-5(G >C) and case C for HbLepore-Hollandia-(δ22/β50) and HbE. The fetuses were found to be HbE trait in case A and HbLepore trait in case B and C. Accurate genotyping of the couple at risk referred for prenatal diagnosis is important to identify uncommon genotypic combinations in compound heterozygous cases. Extended family studies are often useful to avoid misdiagnosis of the fetus. © 2012 John Wiley & Sons, Ltd.

  4. Characterization of a Novel Anti-Human HB-EGF Monoclonal Antibody Applicable for Paraffin-Embedded Tissues and Diagnosis of HB-EGF-Related Cancers.

    PubMed

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

    2016-04-01

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

  5. 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.

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

    PubMed Central

    Tangjaidee, Thongchai; Hatairaktham, Suneerat; Charoensakdi, Ratiya; Panichkul, Narumol; Siritanaratkul, Noppadol; Fucharoen, Suthat

    2013-01-01

    β-thalassemia/Hb E is known to cause oxidative stress induced by iron overload. The glutathione system is the major endogenous antioxidant that protects animal cells from oxidative damage. This study aimed to determine the effect of disease state and splenectomy on redox status expressed by whole blood glutathione (GSH)/glutathione disulfide (GSSG) and also to evaluate glutathione-related responses to oxidation in β-thalassemia/Hb E patients. Twenty-seven normal subjects and 25 β-thalassemia/Hb E patients were recruited and blood was collected. The GSH/GSSG ratio, activities of glutathione-related enzymes, hematological parameters, and serum ferritin levels were determined in individuals. Patients had high iron-induced oxidative stress, shown as significantly increased serum ferritin, a decreased GSH/GSSG ratio, and increased activities of glutathione-related enzymes. Splenectomy increased serum ferritin levels and decreased GSH levels concomitant with unchanged glutathione-related enzyme activities. The redox ratio had a positive correlation with hemoglobin levels and negative correlation with levels of serum ferritin. The glutathione system may be the body's first-line defense used against oxidative stress and to maintain redox homeostasis in thalassemic patients based on the significant correlations between the GSH/GSSH ratio and degree of anemia or body iron stores. PMID:24223032

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

    PubMed Central

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

    2011-01-01

    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. PMID:22089616

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. Treating sickle cell disease by targeting HbS polymerization

    PubMed Central

    Bunn, H. Franklin

    2017-01-01

    Although the root cause of sickle cell disease is the polymerization of hemoglobin S (HbS) to form fibers that make red cells less flexible, most drugs currently being assessed in clinical trials are targeting the downstream sequelae of this primary event. Less attention has been devoted to investigation of the multiple ways in which fiber formation can be inhibited. In this article, we describe the molecular rationale for 5 distinct approaches to inhibiting polymerization and also discuss progress with the few antipolymerization drugs currently in clinical trials. PMID:28385699

  17. Effect of Plasmodium falciparum parasitaemia on some haematological parameters in adolescent and adult Nigerian HbAA and HbAS blood genotypes.

    PubMed

    Eteng, M U

    2002-01-01

    To compare the susceptibility of HbAA and HbAS blood genotypes to Plasmodium falciparum in human subjects. Prospective Cross Sectional Study. Department of Biochemistry College of Medical Sciences, University of Calabar, Cross Rivers State, Nigeria. A total of 120 individuals comprising 60 subjects (41 males and 19 females) and 60 patients (33 males and 27 females) aged between 15 and 30 years were enlisted in this study. The susceptibility of the HbAA and HbAS blood genotypes to Plasmodium falciparum in human subjects was based on the frequency of occurrence of parasitaemia and the accompanying haematological changes in each group. Among a sample population of 120 subjects and patients, 86 were HbAA and 34 were HbAS representing 72% and 28% of the sample population. Parasites were detected in the red cells of 15 out of the 34 HbAS subjects i.e. 44% of the group or 13% of the sample population. Compared with the control group, the parasitaemic HbAA group had significantly lower PCV and Hb, and significantly higher serum iron, TIBC and transferrin, but a similar percentage transferrin saturation. All the differences were highly significant (p < 0.001). In the parasitaemic HbAS group, PCV and percentage transferrin saturation were slightly lower while TIBC and transferrin were slightly higher when compared with the control. These differences were not significant. The greater susceptibility of HbAA individuals to Plasmodium falciparum malaria and the enhanced severity of an attack in this group maybe due to low red cell membrane resistance to the invading parasite and a non-hypoxic environment within the red cell which enhances its development.

  18. 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

  19. 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.

  20. 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. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. 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.

  2. Effects of α-Thalassemia on HbA1c Measurement.

    PubMed

    Xu, Anping; Ji, Ling; Chen, Weidong; Xia, Yong; Zhou, Yu

    2016-11-01

    α-Thalassemia is a benign condition that is often present in patients with diabetes mellitus. Here, we evaluated the effects of different genotypes α-thalassemia on HbA1c measurement. A total of 189 samples from nondiabetic patients were analyzed. HbA1c analysis was performed by ion-exchange high-performance liquid chromatography, boronate affinity HPLC, immunoassay, and capillary electrophoresis. Fasting glucose, fructosamin, and HbA2 were also performed. All samples were confirmed by genotyping for thalassemia. In patients with two or three functional α-genes, HbA1c values were not significantly different from those of controls (P > 0.05); however, in individuals with α-thalassemia with one functional α-gene (i.e., HbH disease), HbA1c levels were significantly different from those of controls (P < 0.01). HbA1c values were significantly lower in individuals with HbH disease than in control individuals and patients in the other two α-thalassemia groups. For patients with HbH disease, there were no significant differences in the four HbA1c measurement systems (P > 0.05). In this study, HbA1c values in samples from individuals with two or three functional α-genes basically reflected the normal mean blood glucose level, while those in samples from individuals with one functional α-gene did not. © 2016 Wiley Periodicals, Inc.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. Endogenous PttHb1 and PttTrHb, and heterologous Vitreoscilla vhb haemoglobin gene expression in hybrid aspen roots with ectomycorrhizal interaction

    PubMed Central

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

    2008-01-01

    Present knowledge on plant non-symbiotic class-1 (Hb1) and truncated (TrHb) haemoglobin genes is almost entirely based on herbaceous species while the corresponding tree haemoglobin genes are not well known. The function of these genes has recently been linked with endosymbioses between plants and microbes. In this work, the coding sequences of hybrid aspen (Populus tremula×tremuloides) PttHb1 and PttTrHb were characterized, indicating that the key residues of haem and ligand binding of both genes were conserved in the deduced amino acid sequences. The expression of PttHb1 and PttTrHb was examined in parallel with that of the heterologous Vitreoscilla haemoglobin gene (vhb) during ectomycorrhiza/ectomycorrhizal (ECM) interaction. Both ECM fungi studied, Leccinum populinum and Xerocomus subtomentosus, enhanced root formation and subsequent growth of roots of all hybrid aspen lines, but only L. populinum was able to form mycorrhizas. Real-time PCR results show that the dual culture with the ECM fungus, with or without emergence of symbiotic structures, increased the expression of both PttHb1 and PttTrHb in the roots of non-transgenic hybrid aspens. PttHb1 and PttTrHb had expression peaks 5 h and 2 d after inoculation, respectively, pointing to different functions for these genes during interaction with root growth-improving fungi. In contrast, ECM fungi were not able to enhance the expression of hybrid aspen endogenous haemoglobin genes in the VHb lines, which may be a consequence of the compensating action of heterologous haemoglobin. PMID:18544611

  9. 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.

  10. 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

  11. A Comparison of HbA1c and Fasting Blood Sugar Tests in General Population

    PubMed Central

    Ghazanfari, Zahra; Haghdoost, Ali Akbar; Alizadeh, Sakineh Mohammad; Atapour, Jamileh; Zolala, Farzaneh

    2010-01-01

    Objectives: Early diagnosis of diabetes is crucially important in reduction of the complications. Although HbA1c is an accurate marker for the prediction of complications, less information is available about its accuracy in diagnosis of diabetes. In this study, the association between HbA1c and FBS was assessed through a cross-sectional population-based study. Methods: A random sample of population in Kerman city was selected. The total number was 604 people. Their HbA1c and fasting blood sugar (FBS) were tested. The association between HbA1c and FBS and also their sensitivity, specificity and predictive values in detection of abnormal values of each other were determined. Results: The association of HbA1c with FBS was relatively strong particularly in diabetic subjects. Generally, FBS was a more accurate predictor for HbA1c compared with HbA1c as a predictor of FBS. Although the optimum cutoff point of HbA1c was >6.15%, its precision was comparable with the conventional cutoff point of >6%. Conclusions: In conclusion, FBS sounds more reliable to separate diabetic from non-diabetic subjects than HbA1c. In case of being interested in using HbA1c in screening, the conventional cutoff points of 6% is an acceptable threshold for discrimination of diabetics from non-diabetics. PMID:21566790

  12. [Analysis of clinical phenotypes of compound heterozygotes of Hb J-Bangkok and β-thalassemia].

    PubMed

    Zhao, Ying; Shang, Xuan; Xiong, Fu; Liu, Yan-hui; Lou, Ji-wu; Xu, Xiang-min

    2013-04-01

    To analyze hematological characteristics of compound heterozygotes of Hb J-Bangkok and β-thalassemia, and to explore the influence of Hb J-Bangkok on the phenotype of β-thalassemia. Peripheral blood samples from a patient carrying Hb J-Bangkok and a β-thalassemia mutation, her family members and three sporadic Hb J-Bangkok carriers were collected. RBC analysis and hemoglobin electrophoresis were performed. Genotypes of α- and β-globin genes were analyzed. The father of the proband and the three sporadic cases were single carriers of Hb J-Bangkok. All of them were asymptomatic and have normal hematological parameters except for an abnormal hemoglobin band detected on hemoglobin electrophoresis. The proband was a compound heterozygote for Hb J-Bangkok and β-thalassemia mutation IVS-Ⅱ-654. She presented typical β-thalassemia trait, featuring hypochromic microcytic anemia and increased Hb A₂ level. An abnormal hemoglobin band was also detected. Carriers of Hb J-Bangkok alone are asymptomatic. Co-existence of Hb J-Bangkok and β-thalassemia may not aggravate the phenotype. Therefore, couples with one carrying Hb J-Bangkok and another carrying a β-thalassemia mutation do not require prenatal diagnosis.

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. Neonatal Cyanosis Due to Hemoglobin Variant: Hb F-Sarajevo.

    PubMed

    Lozar-Krivec, Jana; Stepic, Maja; Hovnik, Tinka; Krsnik, Mladen; Paro-Panjan, Darja

    2016-10-01

    Neonatal cyanosis is rarely due to hemoglobin variants with low oxygen affinity. We describe the clinical course and results of molecular genetic analysis of a boy who presented after birth with severe cyanosis. Arterial blood-gas analysis demonstrated a pronounced shift of the oxygen-hemoglobin dissociation curve to the right and molecular genetic analysis revealed a γ-globin variant, Hb F-Sarajevo. The patient presented is the second reported case of neonatal cyanosis due to this mutation, which was first described in 2012 by Zimmermann-Baer and coauthors. With the introduction of universal screening for congenital heart disease, the finding of low oxygen saturation will uncover more neonates with hemoglobinopathies with low oxygen affinity.

  18. Expression of a truncated form of hHb1 hair keratin in human breast carcinomas.

    PubMed Central

    Régnier, C. H.; Boulay, A.; Asch, P. H.; Wendling, C.; Chenard, M. P.; Tomasetto, C.; Rio, M. C.

    1998-01-01

    Human hHb1 belongs to the type II hard keratin family and is physiologically expressed in hair shafts. In the present study, using specific 3' and 5' probes for hHb1, we established that breast carcinomas ectopically express a hHb1 5'-truncated mRNA, and that this transcript is restricted to malignant epithelial cells. Furthermore, an in vitro study indicated that it could be translated. We concluded that, in breast carcinomas, expression of truncated hHb1 is related to epithelial cell transformation. Because the hHb1 gene maps to 12q11-q13, a chromosome region known to present several breakpoints in solid tumours, we propose that the hHb1 gene might represent a target for such alterations. Images Figure 2 Figure 3 Figure 4 Figure 5 PMID:9862577

  19. 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.

  20. 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.

  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. 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.

  3. Interaction of Hb Grey Lynn (Vientiane) [α91(FG3)Leu>Phe (α1)] with Hb E [β26(B8) Glu>Lys] and α(+)-thalassemia: Molecular and Hematological Analysis.

    PubMed

    Singha, Kritsada; Fucharoen, Goonnapa; Fucharoen, Supan

    2015-01-01

    Hemoglobin (Hb) Grey Lynn is a Hb variant caused by a mutation at codon 91 of α1-globin gene whereas Hb E is a common β-globin chain variant among Southeast Asian population. We report two hitherto undescribed conditions of Hb Grey Lynn found in Thai individuals. The study was done on two unrelated Thai subjects. Hematological parameters were recorded and Hb analysis was carried out using automated Hb analyzers. Mutations were identified by DNA analysis. Hematological features of the patients were compared with those of various forms of Hb Grey Lynn documented previously. Hb and DNA analyses identified a heterozygous Hb Grey Lynn in one patient and a double heterozygous Hb Grey Lynn and Hb E with α(+)-thalassemia in another. Interaction of α(Grey Lynn) with β(E) chains leads to the formation of a new Hb variant, namely the Hb Grey Lynn E (α(GL)2β(E)2), detectable by liquid chromatography (10.3%) but masked by Hb E on capillary electrophoresis. Interaction of these multiple globin gene defects could lead to complex hemoglobinopathies requiring combined analysis with multiple Hb analyzers followed by DNA testing to provide accurate diagnosis of the cases.

  4. 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).

  5. 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

  6. [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

  7. 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

  8. [Genotypes and clinical features of 595 children with HbH disease in Guangxi, China].

    PubMed

    He, Sheng; Zhang, Qiang; Chen, Bi-Yan; Huang, Peng; Tang, Yan-Qing; Wei, Yuan; Chen, Qiu-Li; Zheng, Chen-Guang

    2015-09-01

    To investigate the genotypes and clinical features of children with HbH disease in Guangxi Zhuang Autonomous Region, China. A total of 595 children from Guangxi were recruited. Single-tube multiplex polymerase chain reaction combined with agarose gel electrophoresis, as well as reverse dot blotting, were performed to detect the three α-globin gene deletion mutations (--(SEA), -α(3.7), and -α(4.2)) and three non-deletion mutations (Hb Westmead, Hb Constant Spring, and Hb Quong Sze) which are common in the Chinese population. Among the 595 cases, five common genotypes were identified, which were --(SEA)/-α(3.7) (232 cases), --(SEA)/α(CS)α (174 cases), --(SEA)/-α(4.2) (122 cases), --(SEA)/α(WS)α (35 cases), and --(SEA)/α(QS)α (24 cases). The genotype of THAI deletion associated with α-thalassemia-2 was detected in eight cases. Six β-mutations including CD41-42, CD17-28, CD26, IVS-II-654, IVS-I-1, and CD27-28 were identified in 23 cases. All children with HbH disease had microcytic hypochromic anemia; children with HbH-CS disease had the most severe anemia, and those with HbH-WS disease had the mildest anemia. Deletional HbH disease is the main type in children with HbH disease in Guangxi, and some patients also have mild beta-thalassemia. Non-deletional HbH disease shows more severe phenotype than deletional HbH disease.

  9. 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

  10. 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.

  11. 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.

  12. 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

  13. Five variants of the beta-globin gene without clinical or hematological effects: Hb Maryland [beta 47(CD6)Asp-->His], Hb Kent [beta 37(C3)Trp-->Cys], Hb Visayan [beta 136(H14)Gly-->Cys], Hb Cutlerville [beta 138(H16)Ala-->Val] and Hb Hornchurch [beta 43(CD2)Glu-->Lys].

    PubMed

    Hoyer, James D; Kaur, Prabhjot; Kozak, Elizabeth A; Lum, Sophia; Alter, David N

    2008-01-01

    We report on five hemoglobin (Hb) beta chain variants that were initially identified either by electrophoretic, chromatographic or isoelectric focusing (IEF) methods. These variants do not appear to be associated with clinical or hematological abnormalities. All variants were confirmed by DNA sequence analysis.

  14. Association of Hb Thailand [α56(E5)Lys→Thr] and Hb Phnom Penh [α117(GH5)-Ile-α118(H1)] with α(0)-thalassemia: molecular and hematological features and differential diagnosis.

    PubMed

    Singha, Kritsada; Srivorakun, Hataichanok; Fucharoen, Goonnapa; Changtrakul, Yossombat; Komwilaisak, Patcharee; Jetsrisuparb, Arunee; Puangplruk, Rawiwan; Fucharoen, Supan

    2013-01-01

    We report the molecular and hematological characteristics of two rare hemoglobin (Hb) variants found in associations with a common α(0)-thalassemia (α(0)-thal) in Thai patients. The first case (P1) was a generally healthy 27-year-old man discovered during our ongoing thalassemia screening program. Hemoglobin and DNA analyses identified a previously undescribed condition of compound heterozygosity for Hb Thailand [α56(E5)Lys→Thr] and α(0)-thal (SEA deletion). The second case (P2) was a 4-year-old boy with hypochromic microcytic anemia. Hemoglobin and DNA analyses also identified a compound heterozygosity for Hb Phnom Penh [α117(GH5)-Ile-α118(H1)] in association with α(0)-thal (SEA deletion). Although Hb H (β(4)) inclusion bodies were observed in both cases, Hb analysis using both high performance liquid chromatography (HPLC) and capillary electrophoresis (CE) did not show Hb H. While the two Hb variants could be recognized on Hb HPLC analysis, their corresponding Hb A(2) derivatives: the Hb A(2)-Thailand and Hb A(2)-Phnom Penh, were clearly observed on CE. Apparently, combination of these two Hb variants with α(0)-thal are not expressed as Hb H disease. The two Hb variants could be confirmed by polymerase chain restriction-restriction fragment length polymorphism (PCR-RFLP) and allele-specific PCR assays.

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

    PubMed

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

    2017-01-01

    Identifying double heterozygosities in Hb E (HBB: c.79 G>A)/- -(SEA) (Southeast Asian) (α-thalassemia-1) (α-thal-1) in patients first diagnosed as carrying Hb E is important in thalassemia control. Low Hb E, mean corpuscular volume (MCV) and mean corpuscular hemoglobin (Hb) (MCH) levels have been observed in this double heterozygosity. However, the cutoff points of these parameters have never been systematically established. Here, we analyzed Hb E and red blood cell (RBC) parameters in 372 Hb E patients grouped by Hb levels, by the status of - -(SEA) and -α(3.7) (α-thal-2; rightward) deletions, to establish the cutoff points. Then, the established cutoff points were evaluated in 184 Hb E patients. It was found that the cutoff points of Hb E, MCV, MCH were significantly dependent on the Hb levels. In the group having Hb levels <10.0 g/dL, the cutoff points of Hb E, MCV and MCH were 21.2%, 64.9 fL and 21.0 pg, respectively, and were 25.6%, 72.8 fL and 23.9 pg, respectively, in the group having Hb levels 10.0-11.9 g/dL. Finally, in the group having Hb levels ≥12.0 g/dL, the cutoff points of Hb E, MCV and MCH were 27.1%, 76.7 fL and 25.3 pg, respectively. Thus, to screen for the double heterozygous Hb E/- -(SEA) anomaly in patients initially diagnosed as carrying Hb E, the Hb levels must be taken into account in choosing the suitable cutoff points of these three parameters.

  16. 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

  17. 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

  18. 75 FR 36152 - Savings Association Holding Company Report H-(b)11

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-24

    ... Office of Thrift Supervision Savings Association Holding Company Report H-(b)11 AGENCY: Office of Thrift... Association Holding Company Report H- (b)11 OMB Number: 1550-0060. Form Number: OTS Form H-(b)11. Regulation... applicable statutes, regulations, and conditions of approval to acquire an insured savings association. Type...

  19. 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.

  20. 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

  1. 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.

  2. 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%…

  3. 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%…

  4. 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

  5. Point mutations which should not be overlooked in Hb H disease.

    PubMed

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

    2016-01-01

    Hb H disease is an alpha-thalassemia (α-thal) syndrome characterized by chronic hemolytic anemia that occurs when three of total four α-globin genes lost their function due to completely deletions or different kind of mutations. We here described 66 patients who have been diagnosed for Hb H disease during the last five years in our center. The genotypes involving point mutations present more severe phenotype than deletional forms that make them of primary important to health management. Hb H subjects carry different α-globin genotypes including deletional and non-deletional mutations showing heterogenous clinical manifestations. The Hb H patients presenting a wide range of phenotype carried different deletional, non-deletional mutations or compound heterozygosity of them. We emphasize the importance of some point mutations responsible for more severe form of Hb H disease in Iranian population and the necessity for consideration of prenatal diagnosis (PND) in high-risk couples.

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

    PubMed Central

    Wang, Lei; Hoffmann, Jana; Watzlawick, Hildegard

    2015-01-01

    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. PMID:26655764

  7. 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. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  8. 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

  9. 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.

  10. Performance of the Hospira Plum A+ (HB) hyperbaric infusion pump.

    PubMed

    Bell, James; Weaver, Lindell K; Deru, Kayla

    2014-01-01

    We evaluated the Hospira Plum A+ (HB) hyperbaric infusion pump under monoplace and multiplace hyperbaric conditions to test pump flow accuracy. Pump flow accuracy was tested in monoplace and multiplace hyperbaric chambers at different rates, fluid viscosities, pressures and volumes. Output was recorded from the pump (programmed) and from graduated cylinders or syringes (actual). The lead acid battery life was recorded for multiplace trials. In monoplace trials to 3.0 atmospheres absolute (atm abs), the pump functioned within the published tolerance of 12.5% at 1 ml/hour (mean deviation +3.3%, range 0.0% to +5.0%) and at faster flow rates (mean deviation -0.4%, range -11.5% to +6.0%). A trial of packed red blood cells (deviation -3.3%) was also within acceptable limits. For all multiplace trials, the pump functioned well within the manufacturer's limits (mean deviation -0.1%, range -0.8% to +0.9%). At the maximum flow rate, the interval to the first battery alarm for two trials was shorter than the duration of a clinical hyperbaric session (first alarm at 82 and 94 minutes). When we examined delivery variances in the compression and decompression phases for monoplace chambers, at 1 ml/hour 25/39 trials (64%) had no measurable infusion volume during compression. Conversely, more than twice the programmed volume was infused during the 10-minute decompression interval (mean 0.40 ml, range 0.32 to 0.60 ml). The tubing compliance effect was also noted, to a lesser degree, in trials at 3 and 5 ml/hour. This infusion pump can be useful in hyperbaric medicine departments that treat patients who need intravenous infusions. Tubing compliance may affect fluid volumes delivered by the pump, especially when delivery rates are low. Careful monitoring of patients with low volume infusions during monoplace chamber compression and decompression is advised.

  11. 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.

  12. 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.

  13. Hb mass measurement suitable to screen for illicit autologous blood transfusions.

    PubMed

    Pottgiesser, Torben; Umhau, Markus; Ahlgrim, Christoph; Ruthardt, Sebastian; Roecker, Kai; Schumacher, Yorck Olaf

    2007-10-01

    An increase of hemoglobin (Hb) mass is the key target of blood doping practices to enhance performance as it is a main determinant of maximal oxygen uptake. Although detection methods exist for doping with recombinant EPO and homologous blood transfusions, autologous transfusions remain virtually undetectable. In this context, the most sensitive parameter would be a determination of Hb mass itself. The purpose therefore was to establish whether Hb mass measurements by the optimized CO-rebreathing method allow screening for the withdrawal and reinfusion of autologous red blood cells. The optimized CO-rebreathing method was used for evaluation of Hb mass in two groups at three time points (duplicate measurements: 1) baseline, 2) after donation, and 3) after reinfusion). Group I (N = 6) was to donate and receive 1 unit of packed red cells (PRC) in contrast to two PRC in group II (N = 4). The time span between withdrawal and reinfusion was 2 d. The mean Hb content of the blood units was 59.0 +/- 3.9 g (group I) and 108.3 +/- 1.3 g (group II). Hb mass decreased significantly after blood withdrawal (-89 +/- 16 g in group I and -120 +/- 14 g in group II) and increased significantly after reinfusion (group I: 70 +/- 16 g; group II: 90 +/- 9 g) but was lower than at baseline (group I: -19 +/- 17 g; group II: -30 +/- 14 g). The total error of measurements for the duplicate measures ranged between 0.8 and 3.1% (Hb mass: 6.4-22.1 g). Hb mass determination with the optimized CO-rebreathing method has sufficient precision to detect the absolute differences in Hb mass induced by blood withdrawal and autologous reinfusion. Thus, it may be suited to screen for artificially induced alterations in Hb mass.

  14. 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.

  15. 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.

  16. 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

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

    PubMed

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

    2016-01-01

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

  18. 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.

  19. 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.

  20. 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%.

  1. Multicenter Evaluation of a New High-Throughput HbA1c Testing Platform.

    PubMed

    Imdahl, R; Roddiger, R; Casis-Saenz, E

    2016-12-01

    This non-interventional, multicenter study with anonymized leftover patient samples was performed to evaluate the reliability and analytical performance of the novel high-throughput HbA1c cobas c 513 analyzer. A performance evaluation was carried out at three sites to validate the overall system functionality, user interaction and analytical performance of the new cobas c 513 analyzer using the Tina-quant® HbA1c Gen. 3 assay. HbA1c applications for both whole blood and hemolysate samples show a high precision using both quality control materials and pools of whole blood or hemolysates. The method comparison of HbA1c Gen. 3 on the cobas c 513 with HbA1c Gen. 2 on the Menarini HA-8180V using 249 whole blood samples shows high concordance. Moreover, analyte concentrations as measured by the cobas c 513 and Tosoh G8 and HbA1c Gen. 2 on COBAS INTEGRA® 800 CTS are comparable. The cobas c 513 has proven to be a reliable system with excellent analytical performance of the Tinaquant® HbA1c Gen. 3 assay in high throughput laboratories.

  2. 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.

  3. 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.

  4. Association Between HbA1c Level and Hearing Impairment in a Nondiabetic Adult Population.

    PubMed

    Kang, Seok Hui; Jung, Da Jung; Cho, Kyu Hyang; Park, Jong Won; Lee, Kyu-Yup; Do, Jun-Young

    2016-03-01

    The aim of this study was to investigate whether glycosylated hemoglobin (HbA1c) level in nondiabetic patients is associated with hearing impairment in the general Korean population. Data from the Korean National Health and Nutrition Examination Survey 2011-2013 were used in the analyses. Participants were excluded from this study for the following reasons: they could not provide data regarding pure tone audiometry, they had ear disease, they had brain disorders, asymmetric sensory neural hearing loss (HL), or they were younger than 40 years or had diabetes mellitus. Finally, 7449 participants were included in this study. The mean HbA1c levels in the low, middle, and high tertiles were 5.3% ± 0.2%, 5.7% ± 0.1%, and 6.1% ± 0.2%, respectively. The numbers of participants in the low, middle, and high tertiles were 2808, 2509, and 2132, respectively. The low-frequency, mid-frequency, high-frequency, and average hearing thresholds were significantly increased with increasing HbA1c tertile. Linear regression analyses showed that HbA1c level in the nondiabetic participants was associated with components of metabolic syndrome. The mean numbers of metabolic syndrome components in the low, middle, and high HbA1c tertiles were 1.22, 1.53, and 2.02, respectively. The participants in the middle and high HbA1c tertiles had a 1.239- and 1.253-fold increased risk of HL, respectively, compared with those in the low HbA1c tertile. HbA1c level was associated with hearing impairment in the nondiabetic participants of this study. Therefore, the participants with high HbA1c levels should be closely monitored for hearing impairment.

  5. Change of HbA1c reporting to the new SI units.

    PubMed

    Jones, Graham R D; Barker, George; Goodall, Ian; Schneider, Hans-Gerhard; Shephard, Mark D S; Twigg, Stephen M

    2011-07-04

    An international consensus statement recommends that dual reporting of haemoglobin A (HbA(1c)) levels--in the current units (percentage) and Système International (SI) units (mmol/mol)--be used as an interim measure for a 2-year transition period before progressing towards the use of SI units only. This recommendation is supported by the Australasian Association of Clinical Biochemists, the Australian Diabetes Educators Association, the Australian Diabetes Society and the Royal College of Pathologists of Australasia. The SI units are a true measure of HbA(1c) and remove potential confusion between HbA(1c) values and blood glucose values.

  6. 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

  7. Diagnosis of diabetes mellitus using HbA1c in Asians: relationship between HbA1c and retinopathy in a multiethnic Asian population.

    PubMed

    Sabanayagam, Charumathi; Khoo, Eric Y H; Lye, Weng Kit; Ikram, M Kamran; Lamoureux, Ecosse L; Cheng, Ching Yu; Tan, Maudrene L S; Salim, Agus; Lee, Jeannette; Lim, Su-Chi; Tavintharan, Subramaniam; Thai, Ah-Chuan; Heng, Derrick; Ma, Stefan; Tai, E Shyong; Wong, Tien Y

    2015-02-01

    Hemoglobin A1c (HbA1c) ≥ 6.5% (47.5 mmol/mol) has recently been included as a criterion for the diagnosis of diabetes mellitus. It is unclear whether this criterion is appropriate in Asians. To examine the relationship between HbA1c and diabetes-specific moderate retinopathy in Asian ethnic groups. Four independent population-based cross-sectional studies (2004-2011) in Singapore representing the three major Asian ethnic groups (n = 13 170 adults aged ≥ 25 y: Chinese, 5834; Malays, 3596; and Indians, 3740). Moderate retinopathy was assessed from digital retinal photographs and defined as a level >43 using the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. Sensitivity, specificity, positive and negative predictive values, and the area under the receiver operating characteristic curve for detecting moderate retinopathy were compared across ethnic groups at different HbA1c cut-points. HbA1c levels were higher in Indians and Malays compared to Chinese (P < .001). The prevalence of moderate retinopathy below HbA1c <6.5% was <1% in all ethnic groups. At HbA1c ≥ 6.5%, the sensitivity for detecting moderate retinopathy was lower in Chinese subjects compared to Indians and Malays (75.8 vs 86.0 and 85.3%), but specificity (89.7 vs 71.9 and 76.3%) was higher; however, positive predictive value and negative predictive value were similar among Chinese, Indians, and Malays (10.5, 12.3, 12.4%; and 99.6, 99.1, 99.2%, respectively). The AUCs were similar across all three ethnic groups (0.861, 0.851, and 0.853). Our study supports the use of HbA1c for diagnosing diabetes in Asians. Despite some interethnic variation in the relationship of HbA1c and retinopathy, a cut-point of 6.5% performs reasonably well in the three major Asian ethnic groups.

  8. 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.

  9. 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.

  10. First observation of Hb D-Ouled Rabah [beta19(B1)Asn>Lys] in the Turkish population.

    PubMed

    Köseler, Aylin; Bahadır, Anzel; Koyuncu, Hasan; Atalay, Ayfer; Atalay, Erol Ömer

    2008-03-05

    Hb D-Ouled Rabah [beta19(B1)Asn>Lys] is a rare hemoglobin (Hb) beta chain variant reported from Tuareg tribes in Algeria and once from China. It was suggested that Hb D-Ouled Rabah might be specific of Berber-speaking populations. Our report describes the first observation of this hemoglobin variant in the Turkish population.

  11. 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

  12. 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.

  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. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. Potential use of cord blood for Hb E hemoglobinopathy screening programme using capillary electrophoresis.

    PubMed

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

    2016-12-01

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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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.

  11. 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.

  12. 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

  13. Hb D-Los Angeles [beta121(GH4)Glu>Gln] and Hb Beograd [beta121(GH4)Glu>Val]: Implications for their laboratory diagnosis and genetic origins.

    PubMed

    Bahadır, Anzel; Köseler, Aylin; Atalay, Ayfer; Koyuncu, Hasan; Akar, Ece; Akar, Nejat; Atalay, Erol Ömer

    2009-03-05

    The aim of this study was to determine the laboratory diagnosis and genetic origins of the hemoglobin (Hb) variants, Hb D-Los Angeles and Hb Beograd observed frequently in our region. Hb variants were investigated in one Hb D-Los Angeles and two Hb Beograd families. These families were unrelated with each other. For the determination of Hb variants, alkaline/acid electrophoresis, HPLC, DE-52 micro-column chromatography procedures were applied. Mutations were determined by non-radioactive fluorescence automated DNA sequencing. Beta globin gene cluster haplotypes were identified by RFLP analysis at seven loci known as ε-Hinc II, Gγ-Hind III, AΨβ-Hind III, 5'Ψβ-Hinc II, 3'Ψβ-Hinc II, β-Ava II ve 3'β-Hinf I. Three novel beta globin gene cluster haplotypes were identified as in relation with Hb D-Los Angeles [--+-+++], Hb Beograd [+----++ and -+-(+/-)(+/-)+(+/-)]. These haplotypes were reported for the first time in the world population Conclusion: In this study we emphasize the importance of DNA seqeuncing and other laboratory procedures for the identification of Hb variants in premarital diagnosis. On the other hand we discuss also the genetic origins of these Hb variants.

  14. 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.

  15. 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.

  16. 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.

  17. HbA1c for diagnosis and prognosis of gestational diabetes mellitus.

    PubMed

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

    2015-10-01

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

  18. 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

  19. 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.

  20. Analytical performances of the D-100TM hemoglobin testing system (Bio-Rad) for HbA1c assay.

    PubMed

    Jaisson, Stéphane; Leroy, Nathalie; Guillard, Emmanuelle; Desmons, Aurore; Gillery, Philippe

    2015-08-01

    Glycated hemoglobin (HbA1c) is widely used for the monitoring of glycemic balance in diabetic patients and has also been proposed as a tool for the diagnostic of diabetes mellitus. Accordingly, HbA1c quantification must be performed using robust, reliable and efficient methods. Here are reported the results of the evaluation of a new high performance liquid chromatography (HPLC) system for HbA1c quantification, the D-100TM system from Bio-Rad Laboratories. The analytical performances of the method as well as the influence of the most frequent interferences regarding HbA1c assays (e.g., labile HbA1c, carbamylated hemoglobin, high HbF) have been tested. Intra- and between-assay CVs were respectively lower than 0.93% and 1.46% (HbA1c results expressed in NGSP units) and lower than 1.67% and 2.27% (HbA1c results expressed in IFCC units). The linearity proved to be excellent from 15 mmol/mol (3.5%) to 184 mmol/mol (19.0%) (r=0.999). The results were well correlated with those obtained by another HPLC method (VARIANTTM II Hemoglobin A1c Program reorder pack 270-2101NU-Bio-Rad): HbA1c[VARIANTTM II, mmol/mol]=1.013×HbA1c[D-100TM, mmol/mol]+0.637 (r=0.993, n=2000). The D-100TM system provided results consistent with IFCC-assigned external quality control samples and the presence of labile HbA1c, carbamylated hemoglobin and HbF did not interfere with HbA1c measurement. The D-100 TM system proved to be a robust and reliable method for HbA1c measurement suitable for routine practice in clinical chemistry laboratories.

  1. HbE/β-Thalassemia and Oxidative Stress: The Key to Pathophysiological Mechanisms and Novel Therapeutics.

    PubMed

    Hirsch, Rhoda Elison; Sibmooh, Nathawut; Fucharoen, Suthat; Friedman, Joel M

    2017-05-10

    Oxidative stress and generation of free radicals are fundamental in initiating pathophysiological mechanisms leading to an inflammatory cascade resulting in high rates of morbidity and death from many inherited point mutation-derived hemoglobinopathies. Hemoglobin (Hb)E is the most common point mutation worldwide. The β(E)-globin gene is found in greatest frequency in Southeast Asia, including Thailand, Malaysia, Indonesia, Vietnam, Cambodia, and Laos. With the wave of worldwide migration, it is entering the gene pool of diverse populations with greater consequences than expected. While HbE by itself presents as a mild anemia and a single gene for β-thalassemia is not serious, it remains unexplained why HbE/β-thalassemia (HbE/β-thal) is a grave disease with high morbidity and mortality. Patients often exhibit defective physical development, severe chronic anemia, and often die of cardiovascular disease and severe infections. Recent Advances: This article presents an overview of HbE/β-thal disease with an emphasis on new findings pointing to pathophysiological mechanisms derived from and initiated by the dysfunctional property of HbE as a reduced nitrite reductase concomitant with excess α-chains exacerbating unstable HbE, leading to a combination of nitric oxide imbalance, oxidative stress, and proinflammatory events. Additionally, we present new therapeutic strategies that are based on the emerging molecular-level understanding of the pathophysiology of this and other hemoglobinopathies. These strategies are designed to short-circuit the inflammatory cascade leading to devastating chronic morbidity and fatal consequences. Antioxid. Redox Signal. 26, 794-813.

  2. A Family with γ-Thalassemia and High Hb A2 Levels.

    PubMed

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

    2016-06-01

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

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

    PubMed

    Simonis-Bik, Annemarie M C; Eekhoff, Elisabeth M W; Diamant, Michaela; Boomsma, Dorret I; Heine, Rob J; Dekker, Jacqueline M; Willemsen, Gonneke; van Leeuwen, Marieke; de Geus, Eco J C

    2008-12-01

    In an extended twin study we estimated the heritability of fasting HbA1c and blood glucose levels. Blood glucose was assessed in different settings (at home and in the clinic). We tested whether the genetic factors influencing fasting blood glucose levels overlapped with those influencing HbA1c and whether the same genetic factors were expressed across different settings. Fasting blood glucose was measured at home and during two visits to the clinic in 77 healthy families with same-sex twins and siblings, aged 20 to 45 years. HbA1c was measured during the first clinic visit. A 4-variate genetic structural equation model was used that estimated the heritability of each trait and the genetic correlations among traits. Heritability explained 75% of the variance in HbA1c. The heritability of fasting blood glucose was estimated at 66% at home and lower in the clinic (57% and 38%). Fasting blood glucose levels were significantly correlated across settings (0.34 < r < 0.54), mostly due to a common set of genes that explained between 53% and 95% of these correlations. Correlations between HbA1c and fasting blood glucoses were low (0.11 < r < 0.23) and genetic factors influencing HbA1c and fasting glucose were uncorrelated. These results suggest that in healthy adults the genes influencing HbA1c and fasting blood glucose reflect different aspects of the glucose metabolism. As a consequence these two glycemic parameters can not be used interchangeably in diagnostic procedures or in studies attempting to find genes for diabetes. Both contribute unique (genetic) information.

  4. 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.

  5. 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.

  6. 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

  7. Recent achievements with a cryogenic ultra-lightweighted HB-Cesic mirror

    NASA Astrophysics Data System (ADS)

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

    2010-07-01

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

  8. 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.

  9. [Assays of HbA1c and Amadori products in human biology].

    PubMed

    Gillery, P

    2014-09-01

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

  10. Investigation of local heterogeneity of hbO2 and hb in working dog heart in situ under isovolemic hemodilution and critical coronary stenosis

    NASA Astrophysics Data System (ADS)

    Krug, Alfons; Kessler, Manfred D.; Khuri, Raja; Lust, Robert; Chitwood, Randolph

    1996-12-01

    A tissue spectrophotometer (EMPHO II) working with 70 micrometer micro lightguide sensors enables recording of spectra in the visible wavelength range (500 - 630 nm). During an initial period arterial hypoxia and hyperoxia were induced on working dog heart by mechanical ventilation with oxygen fractions (fiO2) of 0.1 and 0.5. Under these conditions the effects of low and high fiO2 on oxygenation distribution of intracapillary hemoglobin were investigated. In the second part of the experiment the relation between systemic hematocrit, local hemoglobin concentration, local hemoglobin oxygenation and the oxygen regulation mechanism were studied in detail. In the final part of the experiment the effect of critical coronary stenosis on hb and hbO2 was measured. Critical stenosis was achieved by partial clamping of the left anterior coronary artery (LAD).

  11. 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.

  12. 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

  13. Observation of soft X-ray emission from the supernova remnant HB9

    NASA Technical Reports Server (NTRS)

    Tuohy, I. R.; Clark, D. H.; Garmire, G. P.

    1979-01-01

    The number of known X-ray emitting supernova remnants in our galaxy has significantly grown as a result of the soft X-ray survey by the HEAO-1 spacecraft. The HEAO-1 A-2 experiment has observed soft X-ray emission from the old supernova remnant HB9 which lies close to the previously identified X-ray source, Capella. Spectral data and the low optical obscuration in the direction of the remnant suggest that HB9 is a good candidate for detecting Fe XIV coronal forbidden-line emission. Mapping of the coronal line emission in association with the imaging X-ray data expected from HEAO-2 would allow the temperature profile of the emitting shell to be determined in a manner similar to that used by Tuohy, Nousek, and Garmire (1979) for the Cygnus Loop, which is in a similar evolutionary phase to HB9.

  14. 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.

  15. 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

  16. 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.

  17. Glycated hemoglobin (HbA1c): old dogmas, a new perspective?

    PubMed

    Lippi, Giuseppe; Targher, Giovanni

    2010-05-01

    The hemoglobin A1c (HbA1c) assay provides a reliable measure of chronic glycemia and correlates well with the risk of long-term diabetes complications, so that it is currently considered the test of choice for monitoring and chronic management of diabetes. Recently, HbA1c testing has been included within the diagnostic criteria recommended for diagnosis of diabetes in nonpregnant individuals by the American Diabetes Association (ADA). The emerging concept that HbA1c can be used rather than blood glucose in the diagnosis of diabetes is highly appealing for a variety of reasons, including less sensitivity to preanalytical variables, lower within subject biological variability, little to null interference from diurnal variations, acute stress and common drugs which are known to influence glucose metabolism, as well as the fact that one single measurement might provide information for both diagnosing diabetes and tracking glycemic control. On the other hand, the use of HbA1c for screening and diagnosing diabetes also carries some limitations, including the worse diagnostic performance in different populations (i.e., pregnancy, elderly and non-Hispanic blacks), the risk of overdiagnosis in subjects with iron deficiency anemia, in subjects genetically predisposed to hyperglycation, and in those with increased red blood cell turnover. There is also a higher risk of misdiagnosis in patients with end-stage renal disease and heavy alcohol consumption. Finally, HbA1c testing might be biased due to the interference from several hemoglobin variants, is characterized by a higher imprecision than blood glucose measurement, and is more expensive. This paper will critically summarize the potential advantages and limitations of HbA1c as a recommended test for diagnosing diabetes.

  18. 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

  19. 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

  20. [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.

  1. Complex interaction of Hb E [beta26(B8)Glu-->Lys], Hb Korle-Bu [beta73(E17)Asp-->Asn] and a deletional alpha-thalassemia-1 in pregnancy.

    PubMed

    Siriratmanawong, Nirut; Chansri, Wichuda; Singsanan, Sanita; Fucharoen, Goonnapa; Fucharoen, Supan

    2009-01-01

    A pregnant Thai woman with mild hypochromic microcytic anemia caused by alpha- and beta- globin defects is described. The proband was a 26-year-old pregnant woman discovered through our ongoing thalassemia screening program. Initial hemoglobin (Hb) high performance liquid chromatography (HPLC) analysis revealed a homozygosity for an unknown variant at the D window, inconsistent with results of family analyses. Further Hb analysis using automated capillary zone electrophoresis identified that the proband was in fact a compound heterozygote for Hb E [beta26(B8)Glu-->Lys, GAG>AAG] and another beta chain variant. DNA analysis demonstrated that she carried the Hb Korle-Bu mutation [beta73(E17)Asp-->Asn (GAT>AAT)] in trans to the Hb E and an alpha-thalassemia-1 (alpha-thal-1) with the Southeast Asian (- -(SEA)) deletion. Family studies identified that her father and sister were double heterozygotes for Hb Korle-Bu and alpha-thal-1, whereas her mother was a double heterozygote for Hb E/Hb Constant Spring [Hb CS; alpha142, Term-->Gln (TAA>CAA in alpha2)]. The genotype-phenotype relationship observed in this Thai family with complex hemoglobinopathies and methods for characterization are presented.

  2. 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

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. The amino acid sequence of the alpha chain of HB 2 completes the primary structure of the hemoglobins of the Antarctic fish Notothenia coriiceps neglecta.

    PubMed

    D'Avino, R; Camardella, L; Carratore, V; di Prisco, G

    1990-01-01

    1. The blood of Notothenia coriiceps neglecta (a cold-adapted notothenioid fish, widely distributed in Antarctic waters, and characterized by a relatively low content of erythrocytes and hemoglobin), contains two hemoglobin components, Hb 1 and Hb 2; the amino acid sequences of the beta chain of Hb 1 and Hb 2 are identical. 2. The amino acid sequence of the alpha chain of Hb 2 has been established, thus completing the elucidation of the primary structure of the two hemoglobins.

  8. Isolation and Characterization of Atrazine Mineralizing Bacillus subtilis Strain HB-6

    PubMed Central

    Wang, Jinhua; Zhu, Lusheng; Wang, Qi; Wang, Jun; Xie, Hui

    2014-01-01

    Atrazine is a widely used herbicide with great environmental concern due to its high potential to contaminate soil and waters. An atrazine-degrading bacterial strain HB-6 was isolated from industrial wastewater and the 16S rRNA gene sequencing identified HB-6 as a Bacillus subtilis. PCR assays indicated that HB-6 contained atrazine-degrading genes trzN, atzB and atzC. The strain HB-6 was capable of utilizing atrazine and cyanuric acid as a sole nitrogen source for growth and even cleaved the s-triazine ring and mineralized atrazine. The strain demonstrated a very high efficiency of atrazine biodegradation with a broad optimum pH and temperature ranges and could be enhanced by cooperating with other bacteria, suggesting its huge potential for remediation of atrazine-contaminated sites. To our knowledge, there are few Bacillus subtilis strains reported that can mineralize atrazine, therefore, the present work might provide some new insights on atrazine remediation. PMID:25238246

  9. 75 FR 10863 - Savings Association Holding Company Report H-(b)11

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-09

    ... Office of Thrift Supervision Savings Association Holding Company Report H-(b)11 AGENCY: Office of Thrift... collection. Title of Proposal: Savings Association Holding Company Report H- (b)11. OMB Number: 1550-0060... of approval to acquire an insured savings association. Type of Review: Revision of a currently...

  10. 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.

  11. 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.

  12. Prevention and control of Hb Bart's disease in Guangxi Zhuang Autonomous Region, China.

    PubMed

    He, Sheng; Zhang, Qiang; Li, Dongming; Chen, Shaoke; Tang, Yanqing; Chen, Qiuli; Zheng, Chenguang

    2014-07-01

    To demonstrate the performance of Hb Bart's Disease prevention in Guangxi Zhuang Autonomous Region, China. A prenatal control program for Hb Bart's disease was conducted from January 2006 to December 2012. A total of 17,555 pregnant women were screened for α-thalassemia in our prenatal screening program. Pregnancy at-risk for Hb Bart's disease was offered the choice of direct invasive testing or the non-invasive approach with serial ultrasonography. A total of 1425 at-risk couples attended the prenatal diagnosis. Three hundred ninety couples were screened at our own hospital, and the remaining 1035 couples were referred from other hospitals. Two hundred and three pregnant women chose non-invasive approach, and 1122 chose invasive testing. A total of 365 fetuses were diagnosed with Hb Bart's disease. All cases were finally confirmed by fetal DNA analysis. Eighty-two cases (22.4%) were diagnosed by chorionic villous sampling and 194 (53.2%) by amniocentesis samples. The other 89 (24.4%) cases were performed by cordocentesis. All of the affected pregnancies were terminated. Implementation of a prevention and control program accompanying with a referral system for prenatal diagnosis is technically feasible in Guangxi Zhuang Autonomous Region, China. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. Interpretation of HbA1c : association with mean cell volume and haemoglobin concentration.

    PubMed

    Simmons, D; Hlaing, T

    2014-11-01

    The utility of HbA1c in diabetes diagnosis is reduced in settings associated with altered haemoglobin glycation. We have studied whether HbA1c varies with mean cell volume and mean cell haemoglobin concentration as measures of haemoglobin metabolism. Randomly selected adults from rural Victoria, Australia, were invited for biomedical assessment. After excluding patients with known diabetes and/or serum creatinine ≥ 0.12 mmol/l, 1315 adults were included. Demography, arthropometric measurements, oral glucose tolerance test, analyses of full blood count and HbA1c were undertaken. After adjusting for age, sex, ethnicity, BMI, town and socio-economic status, there were no significant differences in haemoglobin, mean cell volume or mean cell haemoglobin concentration by glycaemic status (defined by oral glucose tolerance test). HbA1c was significantly and independently associated with fasting glucose, town, mean cell haemoglobin concentration, ethnicity, age and BMI among men < 50 years (R² = 33.8%); fasting glucose, 2-h glucose, mean cell haemoglobin concentration and town among men ≥ 50 years (R² = 47.9%); fasting glucose, mean cell volume, mean cell haemoglobin concentration, town, 2-h glucose and age among women < 50 years (R² = 46.3%); fasting glucose, mean cell haemoglobin concentration, mean cell volume and 2-h glucose among women ≥ 50 years (R² = 51.6%). A generalized linear model showed a gradient from an adjusted mean HbA1c of 36 (95% CI 34-38) mmol/mol with a mean cell haemoglobin concentration of ≤ 320 g/l to 30 (95% CI 29-31) mmol/mol with a mean cell haemoglobin concentration of > 370 g/l. The gradient across mean cell volume was negative, but only by 1 mmol/mol (0.1%) HbA1c . A mean HbA1c difference of 5 mmol/mol (0.5%) across the mean cell haemoglobin concentration reference range suggests that an accompanying full blood count examination may be required for its use in the diagnosis of diabetes. Further studies are required to confirm this.

  19. [The value of MCV, MCH and HbA(2) in laboratory screening of thalassemia].

    PubMed

    Li, Li-yan; Li, Qiang; Song, Lan-lin; Jin, Wang-jie; Ma, Zhen-hua; Yu, Yan-hong; Zhong, Mei

    2012-02-01

    To explore the roles of mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and hemoglobin A(2) (HbA(2)) in the laboratory screening of thalassemia, and to find optimal screening modality for different conditions. From September 2008 to May 2011, 1384 subjects underwent thalassemia screening at Department of Obstetrics and Gynecology of Nanfang Hospital. Of them, 1036 cases were diagnosed with thalassemia (408 α-thalassemia, 608 β-thalassemia, and 20 αβ compound thalassemia, thalassemia group) and 348 without thalassemia, non-thalassemia group. All subjects were screened respectively for MCV, MCH and HbA(2). Analyses were performed in all subjects to assess the sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy respectively associated with MCV, MCH and HbA(2) alone, combination of MCV and MCH, and combination of MCV, MCH and HbA(2). (1) In the thalassemia group, the sensitivity of MCV alone was 92.9% (379/408) for α thalassemia, 99.3% (604/608) for β thalassemia and 100.0% (20/20) for αβ compound thalassemia. In the non-thalassemia group, the specificity of MCV alone was 75.0% (261/348). (2) In the thalassemia group, the sensitivity of MCH alone was 92.9% (379/408) in α thalassemia, 99.0% (602/608) in β thalassemia and 100.0% (20/20) in αβ compound thalassemia. In the non-thalassemia group, the specificity of MCH alone was 72.7% (253/348). (3) The sensitivity of Hb A(2) alone was 67.4% (275/408) for α thalassemia, 97.5% (593/608) for β thalassemia, and 100% (20/20) for αβ compound thalassemia while it's specificity was 72.4% (252/348) in the non-thalassemia group. (4) With positive indexes of MCV, MCH and MCV + MCH, when HbA(2) > 3.5% it had a high value in β-thalassemia screening, but when HbA(2) < 2.5% it had little value in α-thalassemia screening. (5) As a single marker, MCV and MCH had better sensitivity, specificity, positive predictive value, negative predictive value and

  20. Association between blood group and susceptibility to malaria and its effects on platelets, TLC, and Hb.

    PubMed

    Burhan, Hira; Hasan, Askari Syed; Mansur-Ul-Haque, Syed; Zaidi, Ghazanfar; Shaikh, Taha; Zia, Aisha

    2016-10-31

    According to the World Health Organization, the estimated number of malaria cases in Pakistan is about 1.5 million. Hematological variables like platelets, total leukocyte count (TLC), and hemoglobin (Hb) need to be evaluated to diagnose malaria in suspects. This study aimed to investigate the association between blood group and susceptibility to malaria and effects on platelets, TLC, and Hb. This was a case-control study with a sample size of 446, of which 224 were malarial cases and 222 were controls. A designated questionnaire was developed to know age, gender, malarial strain, Hb, TLC, platelets, and blood group. Of 224 malarial cases, 213 were P. vivax, and 11 were P. falciparum. There were 58 patients with blood group A, 72 with group B, 69 were O and 23 were AB. There was no significant difference in the blood group of controls compared to malarial patients (p > 0.05). Mean Hb level was 11.5mg/dL in malaria patients and 12.5mg/dL in controls. There was significant difference (p<0.01) in the mean platelet count in malarial (11,7000/μL) and control (24,5000/μL) patients. All blood groups showed similar falls in Hb and platelet levels, showing no significant difference among blood groups (p = 0.79 and p = 0.52, respectively). TLC was not significant between malarial and control groups (p = 0.072). Males were two times susceptible to malaria. There was no significant association between the type of blood group and susceptibility to malaria or developing anemia or thrombocytopenia.

  1. Hb level, iron intake and mortality in Chinese adults: a 10-year follow-up study.

    PubMed

    Shi, Zumin; Zhen, Shiqi; Zhou, Yonglin; Taylor, Anne W

    2017-02-01

    Anaemia is prevalent in developing countries and is commonly Fe deficiency related. We aimed to assess the association between Fe status, Fe intake and mortality among Chinese adults. We prospectively studied 8291 adults aged 20-98 years with a mean follow-up of 9·9 years. All participants were measured for Hb at baseline in 2002. Food intake, measured by 3-d weighed food record (n 2832), and fasting serum ferritin were measured. We documented 491 deaths (including 192 CVD and 165 cancer deaths) during 81 527 person-years of follow-up. There was a U-shaped association between Hb levels and all-cause mortality. Compared with the second quartile of Hb (121 g/l), the first (105) and fourth quartile (144) had hazard ratios (HR) of 2·29 (95 % CI 1·51, 3·48) and 2·31 (95 % CI 1·46, 3·64) for all-cause mortality in women. In men, compared with third quartile of Hb (143 g/l), first (122) and fourth quartiles (154) had 61 and 65 % increased risk of all-cause mortality. Anaemia was associated with an increased risk of all-cause and CVD mortality in men but not in women after adjusting for potential confounders. Low and high Fe intake as percentage of Chinese recommended nutrient intake (RNI) were positively associated with all-cause mortality in women but not in men. In women, across quartiles of relative Fe intake, HR for all-cause mortality were 2·55 (95 % CI 0·99, 6·57), 1·00, 3·12 (95 % CI 1·35, 7·18) and 2·78 (95 % CI 1·02, 7·58). Both low and high Hb levels are related to increased risk of all-cause mortality. Both low and high intake of Fe as percentage of RNI was positively associated with mortality in women.

  2. 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.

  3. K2-EDTA and K3-EDTA Greiner Tubes for HbA1c Measurement.

    PubMed

    Vrtaric, Alen; Filipi, Petra; Hemar, Marina; Nikolac, Nora; Simundic, Ana-Maria

    2016-02-01

    To determine whether K2-ethylenediaminetetraacetic acid (EDTA) and K3-EDTA Greiner tubes could be used interchangeably for glycosylated hemoglobin, type A1C (HbA1c) measurement via the Abbott Laboratories ARCHITECT chemiluminescent microparticle HbA1c assay on the ARCHITECT i2000SR immunoanalyzer at our university hospital. We drew blood from a total of 45 outpatients into plastic Greiner Vacuette tubes, some of which were lined with K2-EDTA and others with K3-EDTA anticoagulant. Data are presented as median and interquartile range values. We used the Wilcoxon test and Passing-Bablok regression for tube comparison. For K2-EDTA tubes median HbA1c concentration was 54 mmol/mol (41 to 71 mmol/mol) and for K3-EDTA tubes 56 mmol/mol (43 to 69 mmol/mol). There was no statistically significant difference between K2-EDTA and K3-EDTA (bias= -1.29 mmol/mol; P = 0.24). Passing-Bablok regression showed that there is no constant and proportional error: y = -0.23 (95% CI[-3.52 to 0.69]) + 1.00( 95% CI[0.98 to 1.06]) x. In this study, we provide evidence for the lack of any clinically and statistically significant bias between K2-EDTA and K3-EDTA HbA1c measurements. Thus, Greiner tubes lined with K2-EDTA and those lined with K3-EDTA can safely be used interchangeably to measure HbA1c via the Abbott Laboratories ARCHITECT assay. © American Society for Clinical Pathology, 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. 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

  5. Labile glycated haemoglobin and carbamylated haemoglobin are still critical points for HbA1c measurement.

    PubMed

    Desmons, Aurore; Jaisson, Stéphane; Leroy, Nathalie; Gillery, Philippe; Guillard, Emmanuelle

    2017-06-15

    Haemoglobin A1c (HbA1c) is a key analyte for the monitoring of glycemic balance in diabetic patients and is used for diabetes diagnosis in many countries. The potential interference of carbamylated haemoglobin (cHb) and labile glycated haemoglobin (LA1c) on HbA1c assays must remain a matter of vigilance. Such a situation has occurred in our laboratory with a kit replacement on the Bio-Rad Variant™ II testing system, a cation-exchange high performance liquid chromatography (HPLC) system. With this method, LA1c and cHb coeluted in a same peak which may have different consequences on HbA1c values. The influence of increasing LA1c and cHb values on HbA1c results was studied with in vitro glycation and carbamylation of samples. Samples from patients with high and normal blood urea concentrations were assayed by HPLC and immunological assay. We observed that the degree of interference greatly varied depending on the nature of the interfering Hb fractions found under the so-called "LA1c peak". Thus, we have decided to apply a decision tree using "LA1c" thresholds depending on: (i) the retention time, (ii) the shape of the peak, (iii) other analytes, like urea. If the peak recognized as "LA1c" is mainly formed by LA1c, we consider that there is no interference until 4%. If the peak is mainly formed by cHb, we consider an interference threshold equal to 2%. This situation reminds that cHb and LA1c remain critical issues in chromatography-based HbA1c assays and that adapted criteria must be set up for result interpretation.

  6. 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.

  7. Red cell life span heterogeneity in hematologically normal people is sufficient to alter HbA1c.

    PubMed

    Cohen, Robert M; Franco, Robert S; Khera, Paramjit K; Smith, Eric P; Lindsell, Christopher J; Ciraolo, Peter J; Palascak, Mary B; Joiner, Clinton H

    2008-11-15

    Although red blood cell (RBC) life span is a known determinant of percentage hemoglobin A1c (HbA1c), its variation has been considered insufficient to affect clinical decisions in hematologically normal persons. However, an unexplained discordance between HbA1c and other measures of glycemic control can be observed that could be, in part, the result of differences in RBC life span. To explore the hypothesis that variation in RBC life span could alter measured HbA1c sufficiently to explain some of this discordance, we determined RBC life span using a biotin label in 6 people with diabetes and 6 nondiabetic controls. Mean RBC age was calculated from the RBC survival curve for all circulating RBCs and for labeled RBCs at multiple time points as they aged. In addition, HbA1c in magnetically isolated labeled RBCs and in isolated transferrin receptor-positivereticulocytes was used to determine the in vivo synthetic rate of HbA1c. The mean age of circulating RBCs ranged from 39 to 56 days in diabetic subjects and 38 to 60 days in nondiabetic controls. HbA1c synthesis was linear and correlated with mean whole blood HbA1c (R(2) = 0.91). The observed variation in RBC survival was large enough to cause clinically important differences in HbA1c for a given mean blood glucose.

  8. 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.

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

    USDA-ARS?s Scientific Manuscript database

    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...

  10. [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.

  11. 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.

  12. 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.

  13. The relationship between HbA₁c and ultrasound plaque textures in atherosclerotic patients.

    PubMed

    Huang, Xiao-Wei; Zhang, Yan-Ling; Meng, Long; Qian, Ming; Zhou, Wei; Zheng, Rong-Qin; Zheng, Hai-Rong; Niu, Li-Li

    2016-07-19

    Diabetes mellitus (DM) is associated to the morphological and componential characteristics of atheromatous plaques. It has proven that plaque textures are related to plaque components and beneficial for atherosclerotic risk stratification. The aim of this study is to compare plaque textures in patients with and without DM, and examine the relationship between HbA1c levels and the ultrasound plaque textures in atherosclerotic patients. A total of 136 participants (among them 66 are diabetic and 70 are non-diabetic) suffering from carotid plaques were included. About 300 texture features were extracted from the ultrasound images of plaques using the algorithms of histogram, absolute gradient, run-length matrix, gray-level co-occurrence matrix, autoregressive model and wavelet transform, respectively. Thirty optimal features were selected by the Fisher coefficient and the mutual information measure. The most discriminating feature (MDF) was obtained from the linear discriminant analysis for the optimal features. Linear regression model was performed to investigate the relationship between HbA1c and MDF. The receiver operating characteristics (ROC) curve was further developed to validate the relation between the estimated HbA1c (models output) and diabetes status. A total of 12 texture features showed statistical difference between patients with and without DM. The MDF was significant higher in non-diabetic patients (0.326 ± 0.049) than diabetic patients (-0.346 ± 0.052) (p < 0.001). The optimal regression model (r = 0.348, p < 0.001) for HbA1c included a constant (p < 0.001) and the MDF (p < 0.001). The areas under ROC curve used to estimate HbA1c was 0.828. The results indicate that there is a quantitative relationship between the HbA1c levels and plaque textures in ultrasonic images of atherosclerotic patients, which may suggest that texture analysis of the ultrasonic image of plaque is a promising method for evaluating the cardiovascular risk caused by DM in

  14. HbA1c and coronary heart disease risk among diabetic patients.

    PubMed

    Zhao, Wenhui; Katzmarzyk, Peter T; Horswell, Ronald; Wang, Yujie; Johnson, Jolene; Hu, Gang

    2014-02-01

    Clinical trials to date have not provided definitive evidence regarding the effects of glucose lowering with coronary heart disease (CHD) risk among diabetic patients. We prospectively investigated the association of HbA1c at baseline and during follow-up with CHD risk among 17,510 African American and 12,592 white patients with type 2 diabetes. During a mean follow-up of 6.0 years, 7,258 incident CHD cases were identified. The multivariable-adjusted hazard ratios of CHD associated with different levels of HbA1c at baseline (<6.0 [reference group], 6.0-6.9, 7.0-7.9, 8.0-8.9, 9.0-9.9, 10.0-10.9, and ≥11.0%) were 1.00, 1.07 (95% CI 0.97-1.18), 1.16 (1.04-1.31), 1.15 (1.01-1.32), 1.26 (1.09-1.45), 1.27 (1.09-1.48), and 1.24 (1.10-1.40) (P trend = 0.002) for African Americans and 1.00, 1.04 (0.94-1.14), 1.15 (1.03-1.28), 1.29 (1.13-1.46), 1.41 (1.22-1.62), 1.34 (1.14-1.57), and 1.44 (1.26-1.65) (P trend <0.001) for white patients, respectively. The graded association of HbA1c during follow-up with CHD risk was observed among both African American and white diabetic patients (all P trend <0.001). Each one percentage increase of HbA1c was associated with a greater increase in CHD risk in white versus African American diabetic patients. When stratified by sex, age, smoking status, use of glucose-lowering agents, and income, this graded association of HbA1c with CHD was still present. The current study in a low-income population suggests a graded positive association between HbA1c at baseline and during follow-up with the risk of CHD among both African American and white diabetic patients with low socioeconomic status.

  15. A novel α(0) -thalassemia deletion in a Greek patient with HbH disease and β-thalassemia trait.

    PubMed

    Phylipsen, Marion; Traeger-Synodinos, Jan; van der Kraan, Martijn; van Delft, Peter; Bakker, Greet; Geerts, Mariska; Kanavakis, Emmanuel; Stamoulakatou, Alexandra; Karagiorga, Markissia; Giordano, Piero C; Harteveld, Cornelis L

    2012-04-01

    To determine the molecular basis in a Greek child suspected of having HbH disease and β-thalassemia trait.   Standard hematology, Hb electrophoresis, and HPLC. Multiplex ligation-dependent probe amplification (MLPA), direct sequencing, and breakpoint characterization by NimbleGen fine-tiling array analysis. The index patient showed a moderate microcytic hypochromic anemia with normal ZPP and elevated HbA(2) , indicative for β-thalassemia trait. However, the moderate microcytic hypochromic anemia along with the observation of HbH inclusions in occasional red blood cells suggested a coexisting α-thalassemia. Molecular analysis indicated that the propositus inherited the β(+) -thalassemia mutation IVS2-745 (c>g) and a novel α(0) -thalassemia deletion from the mother, and the common non-deletion α-thalassemia allele α(2) (-5nt)α from the father. The α(0) -thalassemia deletion, named - -(BGS) , is approximately 131.6 kb in length. It removes the major regulatory elements along with the functional α-globin genes but leaves the theta-gene intact. The compound interaction of a β-thalassemia defect along with a single functional α-globin gene is quite rare. Although patients with HbH/β-thal and simple HbH disease have comparable levels of Hb, the absence of free β-globin chains and thus detectable non-functional HbH means that in HbH/β-thal, the levels of functional Hb are higher, resulting in a better compensated functional anemia. Rare large deletions as the one described here remain undetected by gap-PCR in routine molecular screening. The introduction of MLPA as a diagnostic screening tool may improve laboratory diagnostics for these defects. The use of NimbleGen fine-tiling arrays may give additional information about the precise location of breakpoints. © 2011 John Wiley & Sons A/S.

  16. 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

  17. 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.

  18. Ultra-lightweighted HB-Cesic one-meter mirror demonstrator

    NASA Astrophysics Data System (ADS)

    Krödel, Matthias R.; Hofbauer, Peter

    2010-07-01

    Future space missions, such as SPICA and DARWIN, require large, light-weighted, and stiff mirrors with excellent stability. During the past years, ECM fabricated a number of light-weighted mirrors. However, future large missions require further advances with light-weighting, pushing this technology to the limit possible with recently developed composite materials, new fabrication processes, and innovative designs. In 2009, ECM took steps in this direction by fabricating successfully an ultra-lightweighted HB-Cesic® mirror demonstrator 1 m in size. We demonstrated that HB-Cesic®, due to its extreme light-weighting capability and manufacturing versatility, combined with high stiffness, high mechanical strength, and low CTE at cryogenic temperatures, is able to fully meet the requirements of future large cryogenic space mirrors. In this paper we describe the fabrication process of this demonstrator and its physical characteristics.

  19. HbM methaemoglobinaemia as a rare case of early neonatal benign cyanosis.

    PubMed

    Elboraee, Mohamed Sabry; Clarke, Gwen; Belletrutti, Mark J; Escoredo, Sandra

    2015-10-22

    Early neonatal central cyanosis that is unrelated to cardiopulmonary causes, alerts clinicians to possibility of methaemoglobinaemia. Congenital methaemoglobinaemia due to haemoglobin M is an autosomal dominant disorder characterised by lifelong cyanosis. We report a case presentation and review of diagnostic pitfalls of a newborn who presented with central cyanosis; investigations revealed a low methaemoglobin reductase (2.2 IU/g Hb), with normal maternal levels (9.1 IU/g Hb). Therefore, haemoglobinopathy investigations were completed on the mother and her baby, which showed an α-globin variant in both. The maternal α2 globin gene sequencing showed heterozygosity for haemoglobin M Boston (α58 His → Tyr). 2015 BMJ Publishing Group Ltd.

  20. 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

  1. [Effects of nitrogen and phosphorus fertilizer on atrazine degradation and detoxification by degrading strain HB-5].

    PubMed

    Su, Jun; Zhu, Lu-Sheng; Li, Xu-Hua; Wang, Jun; Xie, Hui; Wang, Jin-Hua; Wang, Qi; Jia, Wen-Tao

    2010-10-01

    An atrazine-degrading strain HB-5 was used as a bacteria for biodegradation. Treatments of soil with nitrogen single, phosphate single and nitrogen phosphate together with HB-5 were carried out for degradation and eco-toxicity test; then, relationship between atrazine degradation rate and soil available nitrogen, available phosphorus were discussed. Atrazine residues were determined by HPLC; available nitrogen was determined with alkaline hydrolysis diffusion method; available phosphorus was determined with 0.5 mol/L-NaHCO3 extraction and molybdenum stibium anti-color method, and toxicity test was carried out with micronucleus test of Vicia faba root tip cells. The results showed that: After separately or together application, nitrogenous and phosphorous fertilizers could significantly accelerate atrazine degradation than soil with HB-5 only. On day 5, the order of atrazine degradation was ANP > AP > AN > A; 7 days later, no statistically significant differences were found between treatments. The available nitrogen and phosphorus level in soil reduced as the degradation rate increased in the soil. The soil of eco-toxicity test results indicated that the eco-toxicity significantly reduced with the degradation of atrazine by HB-5, and the eco-toxicity on treatments of soil with fertilizer were all below the treatments without fertilizer. On day 5, the order of eco-toxicity was ANP < AP < AN < A; 7 days later, all treatments were decreased in control levels. So, adjusting soil nutrient content could not only promote atrazine degradation in soil but also could reduce the soil eco-toxicity effects that atrazine caused. All these results could be keystone of atrazine pollution remediation in contaminated soil in the future.

  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. 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

  4. 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.

  5. Solubilization of tricalcium phosphate by P(3HB) accumulating Azotobacter chroococcum MAL-201.

    PubMed

    Pal Saha, Soma; Bhattacharyya, Swapan; Chakraborty, Hrishikesh

    2014-05-01

    Cells of Azotobacter chroococcum MAL-201 (MTCC 3853) are capable of accumulating the intracellular poly(3-hydroxybutyric acid) [P(3HB)], accounting for 65-71 % of its cell dry weight and also capable of synthesizing the enzyme alkaline phosphatase (APase), when grown in glucose and tricalcium phosphate containing nitrogen-free modified Stockdale medium. The concentration of insoluble phosphate in broth medium was optimized as 0.25 % (w/v) for growth and biosynthesis of APase. However, the suboptimal concentration of phosphate (0.1 %, w/v) appeared as the best suited for accumulation of P(3HB) by the strain. The significant differences were observed in biosynthesis of polymer and APase enzyme under variable phosphate concentrations. Glucose, 3.0 % (w/v) was recorded as the optimum concentration for all of the three parameters. The continuation of APase biosynthesis was observed during the period of significant decline in the cellular content of the polymer in the late phase of growth. In order to study the role of P(3HB), the rate of autodigestion of biopolymer and phosphate solubilization rate (k, mineralization constant) were determined in carbon-free medium under batch cultivation process and the parameters were found to be positively correlated. The maximum phosphate solubilization rate (k = 0.0154) by the strain MAL-201 timed at the 10th hour of incubation when the rate of polymer degradation concomitantly attained its peak corresponding to 87 mg/l/h and then declined gradually. Only a negligible amount of residual polymer remained undigested. These data strongly support the functional role of P(3HB) in response to multinutritional stress condition.

  6. 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.

  7. 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.

  8. 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

  9. FERMI LAT and WMAP observations of the supernova remnant HB 21

    DOE PAGES

    Pivato, Giovanna; Hewitt, John W.; Tibaldo, L.; ...

    2013-12-04

    Here, 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) × 10–11 erg cm–2 s–1. HB 21 is well modeled by a uniform disk centered at l = 88fdg75 ± 0fdg04, b = +4fdg65 ± 0fdg06 with a radius of 1fdg19 ± 0fdg06. 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 withmore » 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 × 1049 erg, while, in a two-zone bremsstrahlung-dominated scenario, the total energy in accelerated particles is ~1 × 1049 erg.« less

  10. Periodontal treatment and HbA1c levels in subjects with diabetes mellitus.

    PubMed

    Altamash, M; Klinge, B; Engström, P-E

    2016-01-01

    It has earlier been reported that individuals with poorly controlled diabetes have severe periodontal disease (PD) compared to well-controlled diabetes. This longitudinal interventional study compared periodontal treatment outcomes with HbA1c level changes in four groups of diabetic and non-diabetic patients with or without PD, respectively. HbA1c, bleeding on probing (BOP), plaque index and periodontal pocket depth (PPD) 4 < 6 mm and ≥6 mm were recorded at baseline to 3 months after non-surgical treatment and 3-6 months for surgical treatment in subjects with or without T2D, and with or without PD. A total of 129 patients were followed from baseline to 6 months. Diabetics with PD and without PD showed reductions in HbA1c levels with a mean value of 0·3% after 3 months and mean values of 1% and 0·8%, respectively, after 6 months. Diabetics with PD showed higher levels of BOP versus non-diabetics without PD (P < 0·01) and versus diabetics without PD (P < 0·05) at baseline. After 6 months, diabetics with PD showed higher number of PPD 4 < 6 mm versus diabetics without PD (P < 0·01) and non-diabetics with PD (P < 0·01). Diabetics without PD showed higher levels of PPD 4 < 6 mm versus non-diabetics without PD (P < 0·01). Surgical and non-surgical periodontal treatment in all groups improved periodontal inflammatory conditions with a decrease in HbA1c levels in a period of three and 6 months. No change was seen in the number of pockets PPD 4 < 6 mm in diabetic subjects with PD after non-surgical and surgical treatment. © 2015 John Wiley & Sons Ltd.

  11. Fermi LAT and WMAP Observations of the Supernova Remnant HB 21

    NASA Astrophysics Data System (ADS)

    Pivato, G.; Hewitt, J. W.; Tibaldo, L.; Acero, F.; Ballet, J.; Brandt, T. J.; de Palma, F.; Giordano, F.; Janssen, G. H.; Jóhannesson, G.; Smith, D. A.

    2013-12-01

    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) × 10-11 erg cm-2 s-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 × 1049 erg, while, in a two-zone bremsstrahlung-dominated scenario, the total energy in accelerated particles is ~1 × 1049 erg.

  12. 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.

  13. 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.

  14. Economic burden of beta-thalassemia/Hb E and beta-thalassemia major in Thai children.

    PubMed

    Riewpaiboon, Arthorn; Nuchprayoon, Issarang; Torcharus, Kitti; Indaratna, Kaemthong; Thavorncharoensap, Montarat; Ubol, Bang-On

    2010-01-30

    Hemoglobin E beta-thalassemia (beta-thalassemia/Hb E) has a variable severity, and the cost of treatment has not been well studied. The aim of this study was to analyze the societal cost of caring for children with beta-thalassemias in Thailand. The study was designed as a prevalence-based cost-of-illness analysis in a societal perspective. Medical records from three public hospitals of children aged 2-18 years with beta-thalassemia/Hb E and homozygous beta-thalassemia were reviewed for direct medical cost determination. For direct non-medical cost and indirect cost, a family member was interviewed. It was found that 201 patients with beta-thalassemia/Hb E (91%) and homozygous beta-thalassemia (9%) were recruited for this study. Ninety-two (46%) were severe thalassemia and 109 (54%) were mild to moderate severity. The annual average cost of treatment was US$950; 59% was direct medical cost, 17% direct non-medical cost, and 24% indirect cost. The costs were differentiated by some potential predictors. Significant predictor variables were: hospital, health insurance scheme, blood transfusion pattern, and iron chelation drug use. The average annual cost per patient was calculated, and the cost model was estimated. These would be applied for national planning, economic evaluation of treatment and prevention interventions, and budget impact analysis.

  15. 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.

  16. Gas Generation Testing of Neptunium Oxide Generated Using the HB-Line Phase IIFlowsheet

    SciTech Connect

    Duffey, J

    2003-08-29

    The hydrogen (H{sub 2}) gas generation rate for neptunium dioxide (NpO{sub 2}) samples produced on a laboratory scale using the HB-Line Phase II flowsheet has been measured following exposure to 75% relative humidity (RH). As expected, the observed H{sub 2} generation rates for these samples increase with increasing moisture content. A maximum H{sub 2} generation rate of 1.8 x 10{sup -6} moles per day per kilogram (mol {center_dot} day{sup -1} kg{sup -1}) was observed for NpO{sub 2} samples with approximately one and one-half times (1 1/2 X) the expected specific surface area (SSA) for the HB-Line Phase II product. The SSA of NpO{sub 2} samples calcined at 650 C is similar to plutonium dioxide (PuO{sub 2}) calcined at 950 C according to the Department of Energy (DOE) standard for packaging and storage of PuO{sub 2}. This low SSA of the HB-Line Phase II product limits moisture uptake to less than 0.2 weight percent (wt %) even with extended exposure to 75% RH.

  17. Analytical evaluation of the ADAMS(™) A1c HA 8180 thalassemia mode high-pressure liquid chromatography analyser for the measurement of HbA2 and HbF.

    PubMed

    Urrechaga, E

    2016-12-01

    ADAMS(™) A1cHA-8180T is a HPLC system; within 3.5 min, it quantifies HbF, HbA2 , and HbA0 and flags abnormal peaks. We evaluate its analytical performance for routine estimation of HbA2 and HbF, and critical tests were performed for identifying β-thalassemia carriers. Trueness imprecision, carry over, linearity, and effect of anemia were evaluated according to ICLH, ICLS, or manufacture's guidelines. Comparison (ADAMS(™) A1c HA-8160T) was performed by running 400 samples from healthy subjects, 30 alpha and 80 beta carriers (range: 1.9-5.7 %). Trueness - HbA2 2.7 %, bias 0.81 %; HbA2 5.8 %, bias 0.38 %. HbA2 4.0% is not affected by Hb in the range 221-40 g/L. Carry over was negligible. Within run: normal control - CV 1.5 %, high control - CV 0.9 %.Within laboratory: normal control - total CV% 1.59%; high control - 0.92 %. Linearity - y = 1.034x - 0.17, R(2 ) = 0.998 (range: 2.8-4.8%).Method comparison - y = 0.93x + 0.22, R(2)  = 0.997. HbF imprecision CVs between 0.66 and 1.24% and trueness between 0 and 2.8%. Linearity - y = 1.088x - 0.27, R(2)  = 0.999 (0.1-5.7%). ADAMS(™) A1c HA-8180T provides a rapid and reliable separation of HbA2 . The measurement is accurate and reproducible, which is needed because of the slight difference between normal and pathological values. The gap in HbA2 values between normal subjects and β-thalassemia carriers makes this an appropriate method for rapid screening for carriers. © 2016 John Wiley & Sons Ltd.

  18. 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

  19. Evaluation of the Interference of Hemoglobin Variant J-Bangkok on Glycated Hemoglobin (HbA1c) Measurement by Five Different Methods.

    PubMed

    Wen, Dong-Mei; Xu, Sheng-Nan; Wang, Wei-Jia; Zhang, Xiu-Ming; Suo, Ming-Huan; Zhang, De-Cai

    2017-09-20

    Objective The interference of the hemoglobin variant (Hb J-Bangkok) was evaluated on 4 different glycated hemoglobin assays and compared with a reference immuno assay. Methods An overall test of coincidence of 2 least-squares linear regression lines was performed to determine whether the presence of Hb J-Bangkok caused a statistically significant difference in HbA1c results compared with a reference immuno assay. Statistical analysis was performed on the difference of the estimated average glucose calculated from HbA1c values and fasting plasma glucose in the Hb J-Bangkok variant group using the different detection systems. Deming regression analysis was used to determinate whether Hb J-Bangkok had a significant interference on HbA1c results using an HbA1c±10% relative bias at 6% and 9% HbA1c as evaluation limits. Results Turbidimetric inhibition immunoassay method, and enzymatic methods were not affected by Hb J-Bangkok. However, Hb J-Bangkok showed statistically significant interference to the two ion-exchange high-performance liquid chromatography methods. Conclusion When performing HbA1c tests, clinical laboratory personnel should identify the Hb variant and select the appropriate methods or use alternative indicators. © Georg Thieme Verlag KG Stuttgart · New York.

  20. Screening for common nondeletional α-thalassemias in Chinese newborns by determination of Hb Bart's using the Sebia Capillarys 2 electrophoresis system.

    PubMed

    Tang, Hai-Shen; Zhou, Jian-Ying; Xie, Xing-Mei; Li, Ru; Liao, Can; Li, Dong-Zhi

    2012-01-01

    The interaction of the nondeletional α-thalassemia (α-thal) mutations with the Southeast Asian double α-globin gene deletion results in nondeletional Hb H (β4) disease. Hb Constant Spring (Hb CS, α142, TAA>CAA at α2) and Hb Quong Sze [Hb QS, α125, CTG>CCG (α2)] are the most common nondeletional α-thalassemias in the Chinese population. These α-globin structural variants are unstable and undetectable by routine hemoglobin (Hb) electrophoresis. The amount of Hb Bart's (γ4) in the cord blood of newborns correlates with the number of α-globin genes that are deleted. We determined the quantity of Hb Bart's in cord blood at birth with the Sebia CapillaryS electrophoresis system. Using Hb Bart's levels at 0.1-2.5% as a cut-off range for nondeletional α-thal diagnosis, we detected 154 individuals in 6,525 newborns. Of the 154 samples, 12 were found to be Hb CS carriers, 10 Hb QS carriers, and one Hb Westmead [α122, CAC>CAG (α2)] carrier. We present the first report of the prevalence of Hb QS in our population.

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. 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

  7. Efficacy and safety of canagliflozin by baseline HbA1c and known duration of type 2 diabetes mellitus.

    PubMed

    Wilding, John P H; Blonde, Lawrence; Leiter, Lawrence A; Cerdas, Sonia; Tong, Cindy; Yee, Jacqueline; Meininger, Gary

    2015-04-01

    Canagliflozin, a sodium glucose co-transporter 2 inhibitor, has demonstrated glycemic improvements across studies of patients with type 2 diabetes mellitus (T2DM). The impact of canagliflozin on HbA1c lowering was assessed by baseline HbA1c and known duration of T2DM. This post hoc analysis pooled data from patients with T2DM enrolled in four 26-week, placebo-controlled, Phase 3 studies of canagliflozin (N=2313). Change in HbA1c from baseline to Week 26 was assessed in the overall population and in subgroups by baseline HbA1c (<8.0%, 8.0%-<9.0%, and ≥9.0%) and known duration of T2DM (<5 years, 5-<10 years, and ≥10 years). Relative to placebo, canagliflozin 100 and 300 mg provided greater HbA1c reductions in the overall population. Progressively larger placebo-subtracted reductions in HbA1c with canagliflozin 100 and 300 mg were seen with increasing baseline HbA1c. HbA1c reductions were similar across subgroups based on known duration of T2DM. Both canagliflozin doses were generally well tolerated across subgroups, with a safety and tolerability profile consistent with that seen in Phase 3 studies. Canagliflozin provided glycemic improvements in patients with T2DM across a range of baseline HbA1c and known duration of T2DM. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Benchmarking by HbA1c in a national diabetes quality register--does measurement bias matter?

    PubMed

    Carlsen, Siri; Thue, Geir; Cooper, John Graham; Røraas, Thomas; Gøransson, Lasse Gunnar; Løvaas, Karianne; Sandberg, Sverre

    2015-08-01

    Bias in HbA1c measurement could give a wrong impression of the standard of care when benchmarking diabetes care. The aim of this study was to evaluate how measurement bias in HbA1c results may influence the benchmarking process performed by a national diabetes register. Using data from 2012 from the Norwegian Diabetes Register for Adults, we included HbA1c results from 3584 patients with type 1 diabetes attending 13 hospital clinics, and 1366 patients with type 2 diabetes attending 18 GP offices. Correction factors for HbA1c were obtained by comparing the results of the hospital laboratories'/GP offices' external quality assurance scheme with the target value from a reference method. Compared with the uncorrected yearly median HbA1c values for hospital clinics and GP offices, EQA corrected HbA1c values were within ±0.2% (2 mmol/mol) for all but one hospital clinic whose value was reduced by 0.4% (4 mmol/mol). Three hospital clinics reduced the proportion of patients with poor glycemic control, one by 9% and two by 4%. For most participants in our study, correcting for measurement bias had little effect on the yearly median HbA1c value or the percentage of patients achieving glycemic goals. However, at three hospital clinics correcting for measurement bias had an important effect on HbA1c benchmarking results especially with regard to percentages of patients achieving glycemic targets. The analytical quality of HbA1c should be taken into account when comparing benchmarking results.

  9. Impact of demographics and disease progression on the relationship between glucose and HbA1c.

    PubMed

    Claussen, Anetta; Møller, Jonas B; Kristensen, Niels R; Klim, Søren; Kjellsson, Maria C; Ingwersen, Steen H; Karlsson, Mats O

    2017-06-15

    Several studies have shown that the relationship between mean plasma glucose (MPG) and glycated haemoglobin (HbA1c) may vary across populations. Especially race has previously been referred to shift the regression line that links MPG to HbA1c at steady-state (Herman & Cohen, 2012). To assess the influence of demographic and disease progression-related covariates on the intercept of the estimated linear MPG-HbA1c relationship in a longitudinal model. Longitudinal patient-level data from 16 late-phase trials in type 2 diabetes with a total of 8927 subjects was used to study covariates for the relationship between MPG and HbA1c. The analysed covariates included age group, BMI, gender, race, diabetes duration, and pre-trial treatment. Differences between trials were taken into account by estimating a trial-to-trial variability component. Participants included 47% females and 20% above 65years. 77% were Caucasian, 9% were Asian, 5% were Black and the remaining 9% were analysed together as other races. Estimates of the change in the intercept of the MPG-HbA1c relationship due to the mentioned covariates were determined using a longitudinal model. The analysis showed that pre-trial treatment with insulin had the most pronounced impact associated with a 0.34% higher HbA1c at a given MPG. However, race, diabetes duration and age group also had an impact on the MPG-HbA1c relationship. Our analysis shows that the relationship between MPG and HbA1c is relatively insensitive to covariates, but shows small variations across populations, which may be relevant to take into account when predicting HbA1c response based on MPG measurements in clinical trials. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Evaluation of the HB&L System for the Microbiological Screening of Storage Medium for Organ-Cultured Corneas.

    PubMed

    Camposampiero, D; Grandesso, S; Zanetti, E; Mazzucato, S; Solinas, M; Parekh, M; Frigo, A C; Gion, M; Ponzin, D

    2013-01-01

    Aims. To compare HB&L and BACTEC systems for detecting the microorganisms contaminating the corneal storage liquid preserved at 31°C. Methods. Human donor corneas were stored at 4°C followed by preservation at 31°C. Samples of the storage medium were inoculated in BACTEC Peds Plus/F (aerobic microorganisms), BACTEC Plus Anaerobic/F (anaerobic microorganisms), and HB&L bottles. The tests were performed (a) after six days of storage, (b) end of storage, and (c) after 24 hours of preservation in deturgescent liquid sequentially. 10,655 storage and deturgescent media samples were subjected to microbiological control using BACTEC (6-day incubation) and HB&L (24-hour incubation) systems simultaneously. BACTEC positive/negative refers to both/either aerobic and anaerobic positives/negatives, whereas HB&L can only detect the aerobic microbes, and therefore the positives/negatives depend on the presence/absence of aerobic microorganisms. Results. 147 (1.38%) samples were identified positive with at least one of the two methods. 127 samples (134 identified microorganisms) were positive with both HB&L and BACTEC. 14 HB&L+/BACTEC- and 6 BACTEC+/HB&L- were identified. Sensitivity (95.5%), specificity (99.8%), and positive (90.1%) and negative predictive values (99.9%) were high with HB&L considering a 3.5% annual contamination rate. Conclusion. HB&L is a rapid system for detecting microorganisms in corneal storage medium in addition to the existing methods.

  11. 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.

  12. Hb Dapu (HBA2: c.52G > T): A Novel Nondeletional α-Thalassemia Mutation.

    PubMed

    Yang, Yu; Li, Dong-Zhi; He, Ping

    2016-08-01

    We report a novel mutation on the α2-globin gene, Hb Dapu [α17(A15)Val →Phe (α2); HBA2: c.52G > T] detected in a Chinese family. This mutation gives rise to a previously undescribed hemoglobin (Hb) variant that was undetectable by electrophoretic or chromatographic methods. The combination of this mutation with an in cis deletion of a double α-globin gene resulting in a mild form of Hb H (β4) disease, is consistent with a thalassemic phenotype associated with the novel mutation.

  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. Comparison of HbA1c analysers: Agilent 1100 HPLC using kits produced by Gordion Diagnostic (Turkey) with Premier Hb9210 using kits produced by Trinity Biotech (USA) in different patient groups.

    PubMed

    Arzuhal, A E; Erden, G; Ucar, F; Yavuz Taslipinar, M; Ozcan, N; Guneyk, A; Bulut, E; Ginis, Z; Ozdemir, S

    2016-08-01

    The aim of this study was to compare the performance of Agilent 1100 HPLC analyser using HbA1c kits manufactured by Gordion Diagnostic (Turkey) with that of Premier Hb9210 using the original kits for the measurement of HbA1c in different patient groups. Subjects were divided into four groups: Group 1 included 140 diabetic and non-diabetic subjects with normal urea and haemoglobin levels; Group 2 included 84 diabetic and non-diabetic subjects with high urea levels; Group 3 included 44 diabetic and non-diabetic subjects with iron deficiency anaemia; and Group 4 included 52 diabetic and non-diabetic subjects with high haemoglobin levels. EP Evaluator Release 8 program was used to evaluate the resultant data. According to the comparison results of the two methods in all groups, there was an excellent correlation between the two methods (R>0.98). Moderate-low correlation was found between increased urea concentration and the difference of the two methods (R= -0.374, p = 0.0005). The difference between the methods was found to be increased with increased urea concentrations. This difference, although statistically significant, was within the permitted limits. The observed correlation between the difference of the two methods and the low and high haemoglobin concentrations was statistically non-significant (R = 0.149, p = 0.3343; R = 0.263, p = 0.0594). We found that Agilent 1100 HbA1c analyser and Gordions' HbA1c kit comply with the clinical requirements and are suitable for HbA1c analysis at high levels of urea and Hb and low levels of Hb in diabetic and non-diabetic patients.

  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. 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 Central

    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. PMID:24244560

  17. 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...

  18. 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.

  19. Glycated hemoglobin (HbA1c) measurement in frozen whole blood depends on baseline values of fresh samples.

    PubMed

    Liotta, Luigi; Di Franco, Alessandra; Pazzagli, Mario; Luconi, Michaela

    2013-01-01

    Glycated hemoglobin (HbA1c) has been recently adopted as a diagnostic marker of type 2 diabetes. However, its usage is currently limited to fresh blood samples. To allow retrospective HbA1c measurement in blood banks developed in large epidemic studies, here, we contribute to validate HbA1c assessment in frozen versus fresh blood samples from a cohort of diabetic/nondiabetic adult subjects. HbA1c was measured by HPLC in 237 fresh whole blood samples and on the same samples after a 12-month storage and a further 6-month-refrozen storage. Mean HbA1c ± SD in fresh, frozen, and refrozen samples was 6.9 ± 1.2, 6.6 ± 1.1, and 6.4 ± 1.0% for the Diabetes Control and Complications Trial and 52 ± 13, 49 ± 12, and 46 ± 11 mmol/mol for the International Federation of Clinical Chemistry and Laboratory Medicine reference, respectively. A significant correlation was found between fresh/frozen and fresh/refrozen (R = 0.994 and 0.993, P < 0.001) samples. HbA1c relative error ratio (%RER) between frozen/refrozen and fresh samples significantly correlated with HbA1c and depended on fresh value range, increasing in the five HbA1c classes (<6.0, 6.0-6.5, 6.5-7, 7-8, ≥8%, corresponding to <42, 42-48, 48-53, 53-64, ≥64 mmol/mol, P < 0.001). In particular, the 6.5% (48 mmol/mol) HbA1c diagnostic cutoff of fresh samples identified two classes reflecting significant differences in %RER (2.8 ± 2.0 and 3.3 ± 1.7; P < 0.05) between frozen and fresh samples. In conclusion, our results demonstrate a high correlation between data from fresh and frozen samples, with a very limited %RER between the two measurements, which increases with baseline HbA1c levels. Accordingly, when analyzing biobank frozen specimens for diagnostic purpose, the effect of the HbA1c range should be taken into account.

  20. 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

  1. Interaction of giant extracellular Glossoscolex paulistus hemoglobin (HbGp) with ionic surfactants: a MALDI-TOF-MS study.

    PubMed

    Oliveira, Marilene Silva; Moreira, Leonardo Marmo; Tabak, Marcel

    2008-03-01

    The giant extracellular hemoglobin of Glossoscolex paulistus (HbGp) is constituted by approximately 144 subunits containing heme groups with molecular masses in the range of 16-19kDa forming a monomer (d) and a trimer (abc), and around 36 non-heme structures, named linkers (L). Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF-MS) analysis was performed recently, to obtain directly information on the molecular masses of the different subunits from HbGp in the oxy-form. This technique demonstrated structural similarity between HbGp and the widely studied hemoglobin of Lumbricus terrestris (HbLt). Indeed, two major isoforms (d(1) and d(2)) of identical proportions with masses of 16,355+/-25 and 16,428+/-24Da, respectively, and two minor isoforms (d(3) and d(4)) with masses around 16.6kDa were detected for monomer d of HbGp. In the present work, the effects of anionic sodium dodecyl sulfate (SDS) and cationic cethyltrimethylammonium chloride (CTAC) on the oligomeric structure of HbGp have been studied by MALDI-TOF-MS in order to evaluate the interaction between ionic surfactants and HbGp. The data obtained with this technique show an effective interaction of cationic surfactant CTAC with the two isoforms of monomer d, d(1) and d(2), both in the whole protein as well as in the pure isolated monomer. The results show that up to 10 molecules of CTAC are bound to each isoform of the monomer. Differently, the mass spectra obtained for SDS-HbGp system showed that the addition of the anionic surfactant SDS does not originate any mass increment of the monomeric subunits, indicating that SDS-HbGp interaction is, probably, significantly less effective as compared to CTAC-HbGp one. The acid pI of the protein around 5.5 is, probably, responsible for this behavior. The results of this work suggest also some interaction of both surfactants with linker chains as well as with trimers, as judged from observed mass increments. Our data are consistent with a recent

  2. 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

  3. A new unstable hemoglobin variant Hb Acharnes or [β53(D4) Ala - Thr]: a case report.

    PubMed

    Karmakar, A; Ghosh, S; Ghosh, T K

    2012-04-01

    Hb Acharnes or [β53(D4) Ala - Thr] is a newly discovered unstable hemoglobin variant. It has been reported in very few literatures across the world and no cases have been reported from India till date. Hb Acharnes is known to interact with β°-thalassemia to produce thalassemia intermedia and heterozygotes may present with borderline HbA2 levels. Here we report a rare case discovered during routine screening of thalassemia and hemoglobinopathies in a 19 year old pregnant lady. To emphasize the diagnostic difficulties and importance of detection of a rare hemoglobin variant Hb Acharnes [β53(D4) Ala - Thr] in an asymptomatic patient in West Bengal, India. The 19 year old asymptomatic pregnant lady P1+0, LMP - 21.01.2011 reported in antenatal OPD of Burdwan Medical College & Hospital, Burdwan, West Bengal, India for routine follow up. After proper antenatal check up her blood was collected as a routine screening for Thalassemia, EDTA blood was taken on 5th April 2011 and was subjected to Hemoglobin estimation by Cyanmethemoglobin method, Cell parameters in automated cell counter (SYSMEX KX21) and Hemoglobin analysis by HPLC in BIORAD VARIANT system. The patient was normal with respect to clinical examination and urinalysis. Routine blood counts revealed mild microcytic hypochromic anemia and on HPLC an unknown band (retention time 2.2 minutes, 21.2%, appearing as a shoulder of HbA0 band) of hemoglobin variant was discovered with normal level of HbF and HbA2. Hemoglobin analysis of her mother showed similar pattern while her father and her husband had normal Hb-HPLC pattern. The unknown hemoglobin variant was identified as Hemoglobin Acharnes or [β53 (D4) Ala - Thr] by the Biorad laboratories upon consulting the standard chromatogram patterns for this particular hemoglobin variant. Only Haemoglobin Electrophoresis by conventional gel technique may miss the case and the HPLC pattern may be used as a standard control for identification.

  4. HbA1c in type 2 diabetes diagnostic criteria: addressing the right questions to move the field forwards.

    PubMed

    Sattar, N; Preiss, D

    2012-06-01

    This commentary aims to move the debate regarding the adoption of HbA(1c) for diagnosis of type 2 diabetes forwards by highlighting the need to avoid addressing irrelevant questions, in particular, comparison of individuals diagnosed with different diagnostic criteria. Instead, we provide a list of important future questions, including whether adoption of HbA(1c) as the primary diagnostic test improves uptake of diabetes screening, with resultant earlier diagnosis and improvement in outcomes.

  5. HbA1c in the diagnosis of diabetes and abnormal glucose tolerance in patients with Graves' hyperthyroidism.

    PubMed

    Yang, Liyong; Shen, Ximei; Yan, Sunjie; Yuan, Xin; Lu, Juanjuan; Wei, Wenfeng

    2013-07-01

    To assess the suitability of HbA1c as a criterion for the diagnosis of diabetes in patients with Graves' disease. This study enrolled 310 patients with untreated newly diagnosed Graves' disease, 208 patients with euthyroid goiter and 329 age-matched (control) subjects without thyroid disease from Fuzhou, China. The performance of HbA1c against the OGTT for diagnosing diabetes was determined. The Framingham risk score was used to assess general cardiovascular disease (CVD) risk. The percentage of patients with abnormal glucose metabolism as classified by HbA1c levels was lower than by OGTT criteria in patients with Graves' disease-33.2% vs. 41.3% for pre-diabetes and 4.5% vs. 11.3% for diabetes, respectively. The sensitivity of HbA1c for diagnosing diabetes in patients with Graves' disease was lower than in patients with euthyroid goiter and subjects without thyroid disease (34.9%, 63.2% and 60.6% respectively), while the specificity was similar (99.3%, 98.6%, 97.4%). Approximately 7.4% of patients with Graves' disease diagnosed with diabetes according to OGTT criteria were misdiagnosed as not having the disease by HbA1c, much higher than that for the other two groups. Patients with Graves' disease with diabetes not diagnosed with the disease by HbA1c showed a high risk for CVD. The low sensitivity of the HbA1c criterion underestimated the percentage of diabetes in patients with Graves' disease. Patients with diabetes who were misdiagnosed as not having the disease by HbA1c were at high risk for CVD. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  6. 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.

  7. 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.

  8. Dose-response association of physical activity with HbA1c: Intensity and bout length.

    PubMed

    Gay, Jennifer L; Buchner, David M; Schmidt, Michael D

    2016-05-01

    The aims of this study were to characterize the dose-response relationship between moderate-to-vigorous intensity physical activity (MVPA), and light-intensity activity with HbA1c in adults at low, moderate, and high risks of type 2 diabetes, and to compare the relationship of short (1 to 9min) versus long (10+min) bouts of MVPA with HbA1c. Data from 2707 participants from the 2003-2006 National Health And Nutrition Examination Survey were analyzed in 2014-2015. Type 2 diabetes risk was classified into three groups based upon age (<40years; ≥40years) and BMI (<30; ≥30). The relationship between HbA1c and accelerometer-based physical activity variables was assessed using multiple regression models. There was a curvilinear dose-response relationship between HbA1c with total activity and MVPA in adults at moderate or high risk for type 2 diabetes: higher amounts of physical activity were associated with lower HbA1c. The association of physical activity on HbA1c was stronger at lower levels of physical activity. There was no dose-response relationship in adults at low risk for type 2 diabetes. The relationship between short bouts with HbA1c was stronger than for bouts≥10min. In adults at risk for type 2 diabetes, there is a dose-response relationship between physical activity and HbA1c levels such that the relationship: (1) is curvilinear; (2) is stronger when a higher percent of total activity comes from MVPA; and (3) is more potent with short bouts of MVPA. Fractionalized physical activity of at least moderate-intensity may contribute to long-term glucose control. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    PubMed

    Selvin, Elizabeth; Coresh, Josef; Zhu, Hong; Folsom, Aaron; Steffes, Michael W

    2010-06-01

    The aims of the present study were to demonstrate the reliability of HbA1c measurements during two time periods and to compare these measurements with HbA1c distribution in the general US population. HbA1c was measured in 14,069 whole blood samples in the Atherosclerosis Risk in Communities (ARIC) study using different HPLC instruments across two time periods, namely 2003-2004 and 2007-2008. At the time of measurement, samples had been in storage at -70°C for up to 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. 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 vs 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. Measurements of HbA1c from samples stored for up to 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. © 2010 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Blackwell Publishing Asia Pty Ltd.

  10. Capillarys 2 Flex Piercing: Analytical performance assessment according to CLSI protocols for HbA1c quantification.

    PubMed

    Doggui, Radhouene; Abdelhafidh Sahli, Chaïma; Aissa, Wassef Lotfi; Hammami, Maroua; Ben Sedrine, Maha; Mahjoub, Rahma; Zouaoui, Khemais; Daboubi, Rim; Siala, Hajer; Messaoud, Taieb; Bibi, Amina

    2017-09-01

    HbA1c is used for monitoring diabetic balance. In this paper we report an assessment of the analytical performances of Capillarys 2 Flex Piercing (C2FP) for HbA1c measurement using CE (Capillary Electrophoresis). CLSI (Clinical and Laboratory Standard Institute) protocols are used for the evaluation of apparatus performances: precision, linearity, method comparison, trueness and common interferences. HbA1c CVs average in intra-assay was 1.6% between run imprecision CV ranged from 0.1 to 1.8%. The linearity was demonstrated between 4.7 and 15.0%. The comparison study revealed that Bland Altman plot mean difference was equal to -0.03 (CI 95% (-0.05 to -0.0003)) and Passing-Bablok regression intercept was -0.05, CI95%(-0.13 -  -0.05); slope: 1.00, CI95%[1.00-1.01]. A strong correlation (r > 0.99) was proved. No significant effects of hemoglobin variants were seen with CE on HbA1c measurement. No problem related to sample-to-sample carry over was noted. No interferences of LA1c and cHb were observed. CE allowed quantification of HbA1c even at low level of total hemoglobin (40 g/L) in contrast to HPLC. Furthermore, this analyzer offered the opportunity of quantifying the HbA2 simultaneously with HbA1c . This evaluation showed that C2FP is a convenient system for the control of diabetes and the detection of hemoglobinopathies. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. 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.

  12. 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.

  13. 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

  14. Plasma microRNA-451 as a novel hemolytic marker for β0-thalassemia/HbE disease

    PubMed Central

    Leecharoenkiat, Kamonlak; Tanaka, Yuka; Harada, Yasuko; Chaichompoo, Porntip; Sarakul, Orawan; Abe, Yasunobu; Smith, Duncan Richard; Fucharoen, Suthat; Svasti, Saovaros; Umemura, Tsukuru

    2017-01-01

    In Southeast Asia, particularly in Thailand, β0-thalassemia/hemoglobin E (HbE) disease is a common hereditary hematological disease. It is associated with pathophysiological processes, such as the intramedullary destruction of immature erythroid cells and peripheral hemolysis of mature red blood cells. MicroRNA (miR) sequences, which are short non-coding RNA that regulate gene expression in a suppressive manner, serve a crucial role in human erythropoiesis. In the present study, the plasma levels of the erythroid-expressed miRNAs, miR-451 and miR-155, were analyzed in 23 patients with β0-thalassemia/HbE and 16 control subjects. Reverse transcription-quantitative polymerase chain reaction analysis revealed significantly higher levels of plasma miR-451 and miR-155 in β0-thalassemia/HbE patients when compared to the control subjects. Notably, among the β0-thalassemia/HbE patients, a significant increase in miR-451 levels was detected in severe cases when compared with mild cases. The levels of plasma miR-451 correlated with reticulocyte and platelet counts. The results suggest that increased plasma miR-451 levels may be associated with the degree of hemolysis and accelerated erythropoiesis in β0-thalassemia/HbE patients. In conclusion, miR-451 may represent a relevant biomarker for pathological erythropoiesis associated with β0-thalassemia/HbE. PMID:28447765

  15. Misdiagnosis of Hb D-Punjab/β-thalassemia is a potential pitfall in hemoglobinopathy screening programs: a case report.

    PubMed

    Belhoul, Khawla M; Bakir, Maisam L; Abdulrahman, Mahera

    2013-01-01

    Compound heterozygosity for Hb D-Punjab [β121(GH4)Glu→Gln, GAA>CAA] /β-thalassemia (β-thal) must be carefully differentiated from homozygous Hb D-Punjab in premarital screening. This is essential when the partner is a carrier of β-thal trait. The case of a baby born affected with β-thal major (β-TM), from a marriage between a mother with β-thal trait and a father with Hb D-Punjab/β-thal, is presented. The father had been misdiagnozed as homozygous Hb D-Punjab during premarital screening, even though the screening program utilized complete blood counts and high performance liquid chromatography (HPLC). The factors that may have contributed to this midsiagnosis are presented and discussed. It is recommended that cases of Hb D-Punjab, or any other hemoglobin (Hb) variant appearing as homozygous, are carefully evaluated if microcytic hypochromic parameters not associated with α-thal are present. In all cases of suspected hemizygosis, molecular analysis should always be performed, and in particular if one partner is a β-thal carrier.

  16. 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.

  17. 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.

  18. Characterization of Neptunium Oxide Generated Using the HB-Line Phase II Flowsheet

    SciTech Connect

    Duffey, J

    2003-08-29

    Approximately 98 grams of neptunium(IV) oxide (NpO{sub 2}) were produced at the Savannah River Technology Center (SRTC) for use in gas generation tests to support the neptunium stabilization program at the Savannah River Site (SRS). The NpO{sub 2} was produced according to the anticipated HB-Line flowsheet consisting of anion exchange, oxalate precipitation, filtration, and calcination. Characterization of the NpO{sub 2} product to be used in gas generation tests included bulk and tap density measurements, X-ray diffraction, particle size distribution, specific surface area measurements, and moisture analysis.

  19. Self-knowledge of HbA1c in people with Type 2 Diabetes Mellitus and its association with glycaemic control.

    PubMed

    Trivedi, Hina; Gray, Laura J; Seidu, Samuel; Davies, Melanie J; Charpentier, Guillaume; Lindblad, Ulf; Kellner, Christiane; Nolan, John; Pazderska, Agnieszka; Rutten, Guy; Trento, Marina; Khunti, Kamlesh

    2017-10-01

    The aim of this study was to evaluate the prevalence of accurate self-knowledge of a patient's own HbA1c level (HbA1cSK), as a component of structural education (University Hospital's of Leicester (UHL), 2013) and its association with glycaemic control. Data from the GUIDANCE study, a cross-sectional study involving 7597 participants from eight European countries was used. HbA1cSK was evaluated and compared with laboratory measured HbA1c levels (HbA1cLAB), which represented the measure of glycaemic control. Accuracy of the self-reported HbA1c was evaluated by using agreement statistical methods. The prevalence of HbA1cSK was 49.4%. Within this group, 78.3% of the participants had accurately reported HbA1cSK. There was good level of agreement between HbA1cSK and HbA1cLAB (intra-class correlation statistic=0.84, p<0.0001). Participants with accurately reported HbA1cSK were found to have a statistically significantly lower HbA1cLAB compared to participants with inaccurately reported HbA1cSK (7.0% versus 7.3%, p<0.001). Nearly half of the patients had self-knowledge of their own HbA1c level. Moreover, the participants with accurately reported HbA1cSK were found to have associated better glycaemic control. Copyright © 2017 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

  20. 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.

  1. 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.

  2. Low association between fasting and OGTT stimulated glucose levels with HbA1c in overweight children and adolescents.

    PubMed

    Ehehalt, Stefan; Wiegand, Susanna; Körner, Antje; Schweizer, Roland; Liesenkötter, Klaus-Peter; Partsch, Carl-Joachim; Blumenstock, Gunnar; Spielau, Ulrike; Denzer, Christian; Ranke, Michael B; Neu, Andreas; Binder, Gerhard; Wabitsch, Martin; Kiess, Wieland; Reinehr, Thomas

    2016-11-22

    Diabetes and prediabetes are defined based on different methods such as fasting glucose, glucose at 2-hour in oral glucose tolerance test (OGTT), and glycated hemoglobin A1c (HbA1c). These parameters probably describe different deteriorations in glucose metabolism limiting the exchange between each other in definitions of diabetes. To investigate the relationship between OGTT and HbA1c in overweight and obese children and adolescents living in Germany. Study population: Overweight and obese children and adolescents (n = 4848; 2668 female) aged 7 to 17 years without known diabetes. The study population was stratified into the following subgroups: normal glucose tolerance, prediabetes, diabetes according to OGTT and/or HbA1c categories, confirmed diagnosis of diabetes. In the entire study group fasting plasma glucose (FPG) correlated weakly to 2-hour glucose (r = 0.26), FPG correlated weakly to HbA1c (r = 0.18), and 2-hour glucose correlated weakly to HbA1c (r = 0.17, all P < .001). Patients with confirmed diabetes showed a very high correlation between FPG and 2-hour glucose (r = 0.73, n = 50). Moderate correlations could be found for patients with impaired fasting glucose (2-hour glucose vs HbA1c: r = 0.30, n = 436), for patients with diabetes according to OGTT and/or HbA1c (FPG vs 2-hour glucose: r = 0.43; 2-hour glucose vs HbA1c: r = -0.30, n = 115) and for patients with confirmed diabetes (2-hour glucose vs HbA1c: r = -0.47, all P < .001). Because FPG, 2-hour glucose, and HbA1c correlated only weakly we propose that these parameters, particularly in the normal range, might reflect distinct aspects of carbohydrate metabolism. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Baseline HbA1c to Identify High-Risk Gestational Diabetes: Utility in Early vs Standard Gestational Diabetes.

    PubMed

    Sweeting, Arianne N; Ross, Glynis P; Hyett, Jon; Molyneaux, Lynda; Tan, Kris; Constantino, Maria; Harding, Anna Jane; Wong, Jencia

    2017-01-01

    The increasing prevalence of gestational diabetes mellitus (GDM) necessitates risk stratification directing limited antenatal resources to those at greatest risk. Recent evidence demonstrates that an early pregnancy glycated hemoglobin (HbA1c ≥5.9% (41 mmol/mol) predicts adverse pregnancy outcomes. To determine the optimal HbA1c threshold for adverse pregnancy outcomes in GDM in a treated multiethnic cohort and whether this differs in women diagnosed <24 vs ≥24 weeks' gestation (early vs standard GDM). This was a retrospective cohort study undertaken at the Royal Prince Alfred Hospital Diabetes Antenatal Clinic, Australia, between 1991 and 2011. Pregnant women (N = 3098) underwent an HbA1c (single-laboratory) measurement at the time of GDM diagnosis. Maternal clinical and pregnancy outcome data were collected prospectively. The association between baseline HbA1c and adverse pregnancy outcomes in early vs standard GDM. HbA1c was measured at a median of 17.6 ± 3.3 weeks' gestation in early GDM (n = 844) and 29.4 ± 2.6 weeks' gestation in standard GDM (n = 2254). In standard GDM, HbA1c >5.9% (41 mmol/mol) was associated with the greatest risk of large-for-gestational-age (odds ratio [95% confidence interval] = 2.7 [1.5-4.9]), macrosomia (3.5 [1.4-8.6]), cesarean section (3.6 [2.1-6.2]), and hypertensive disorders (2.6 [1.1-5.8]). In early GDM, similar HbA1c associations were seen; however, lower HbA1c correlated with the greatest risk of small-for-gestational-age (P trend = 0.004) and prevalence of neonatal hypoglycemia. Baseline HbA1c >5.9% (41 mmol/mol) identifies an increased risk of large-for-gestational-age, macrosomia, cesarean section, and hypertensive disorders in standard GDM. Although similar associations are seen in early GDM, higher HbA1c levels do not adequately capture risk-limiting utility as a triage tool in this cohort.

  4. Hyperglycemia, assessed according to HbA1c , and future risk of venous thromboembolism: the Tromsø study.

    PubMed

    Lerstad, G; Brodin, E E; Enga, K F; Jorde, R; Schirmer, H; Njølstad, I; Svartberg, J; Braekkan, S K; Hansen, J-B

    2014-01-01

    HbA1c , a marker of average plasma glucose level during the previous 8-12 weeks, is associated with the future risk of cardiovascular disease and all-cause mortality. To examine the association between hyperglycemia, assessed according to HbA1c , and the future risk of venous thromboembolism (VTE) in a population-based cohort. HbA1c was measured in 16 156 unique subjects (25-87 years) who participated in one or more surveys of the Tromsø study (Tromsø 4, 1994-1995; Tromsø 5, 2001-2002; and Tromsø 6, 2007-2008). All subjects were followed, and incident VTE events were recorded up to 31 December 2010. There were 333 validated first VTE events, of which 137 were unprovoked, during a median follow-up of 7.1 years. HbA1c was not associated with the future risk of VTE in analyses treating HbA1c as a continuous variable, or in categorized analyses. The risk of VTE increased by 5% per one standard deviation (0.7%) increase in HbA1c (multivariable-adjusted hazard ratio [HR] 1.05; 95% confidence interval [CI] 0.97-1.14), and subjects with HbA1c  ≥ 6.5% had a 27% higher risk than those with HbA1c  < 5.7% (multivariable-adjusted HR 1.27; 95% CI 0.72-2.26). There was no significant linear trend for an increased risk of VTE across categories of HbA1c (P = 0.27). Serum levels of HbA1c were not associated with the future risk of VTE in multivariable analysis. Our findings suggest that hyperglycemia does not play an important role in the pathogenesis of VTE. © 2013 International Society on Thrombosis and Haemostasis.

  5. 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.

  6. Whole-cell proteome reference maps of an extreme thermophile, Thermus thermophilus HB8.

    PubMed

    Kim, Kwang; Okanishi, Hiroki; Masui, Ryoji; Harada, Akira; Ueyama, Norikazu; Kuramitsu, Seiki

    2012-10-01

    Thermus thermophilus HB8 is a model microorganism for industrial applications because of its thermophilic enzymes, and for basic bacteriology to understand the coordination of the biological functions of the genome-encoded enzymes at the cellular level. Here, we present 2DE reference maps of T. thermophilus HB8 in the pH ranges 4-7 and 6-11 obtained with whole-cell lysates. PMF analysis using MALDI-TOF-MS and MS/MS analysis using nano-scale LC and quadrupole TOF-MS identified 258 different proteins among the 306 protein spots on 2DE gels. Functional classification indicated that 56%, 16%, and 14% of the identified proteins were related to metabolism, genetic information process, and cellular process, respectively. Detailed classification of the metabolism-related proteins suggested that during the exponential phase, amino acid and carbohydrate metabolism are major metabolic processes, whereas nucleotide and lipid metabolism are minor ones. On the other hand, volume quantification analysis revealed that proteins involved in the translational process, nucleotide metabolism, and central carbon metabolism were most abundantly expressed in the exponential phase. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. 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.

  8. 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.

  9. 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. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. 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.

  11. Heparin-binding epidermal growth factor-like growth factor (HB-EGF) and proteolytic processing by a disintegrin and metalloproteinases (ADAM): a regulator of several pathways.

    PubMed

    Taylor, S R; Markesbery, M G; Harding, P A

    2014-04-01

    HB-EGF is a member of the EGF family of ligands that is initially synthesized as a membrane-bound growth factor termed, proHB-EGF. The membrane bound proHB-EGF undergoes extensive proteolytic processing by several metalloproteinases capable of stimulating cellular proliferation. Soluble, mature HB-EGF binds to and activates EGF receptors. HB-EGF is a critical molecular component to a number of normal physiological processes including but not limited to tissue injury and wound healing, reproduction, angiogenesis and recently, adipogenesis. Misexpression of HB-EGF is linked to tumor formation and cancer including hepatocellular, pancreatic, gastric, breast, colon and melanoma, gliomas and glioblastomas. HB-EGF is a likely tool for therapeutic approaches to enhance treatment of injuries as well as a target for prevention of several cancers and obesity. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Molecular mass of Poly-3-hydroxybutyrate (P3HB) produced by Azotobacter vinelandii is influenced by the polymer content in the inoculum.

    PubMed

    Millán, Modesto; Salazar, Miriam; Segura, Daniel; Castillo, Tania; Díaz-Barrera, Álvaro; Peña, Carlos

    2017-10-10

    Poly-3-hydroxybutyrate (P3HB) is a biopolymer produced by Azotobacter vinelandii. The physicochemical properties and applications of P3HB are strongly influenced by its weight-average molecular mass (Mw), and in A. vinelandii, it could be influenced by the culture conditions. The aim of this study was to evaluate the effect of the P3HB content of the inoculum on the Mw of the polymer produced by A. vinelandii OP in bioreactor cultures. A. vinelandii cells containing 20, 50 and 70% of P3HB were used as inoculum. The P3HB content in the inoculum affected the volumetric P3HB productivity (qP3HB) and the Mw of P3HB. Those cultures inoculated with cells containing 20% of P3HB, achieved the highest qP3HB (0.17±0.018gP3HBL(-1)h(-1)); whereas a P3HB content of 70% was reflected as a low qP3HB (0.021±0.002gP3HBL(-1)h(-1)). On the other hand, using an inoculum with 70% of polymer content, the Mw of the biopolymer remained stable at values close to 3200kDa; whereas, when an inoculum with 20% of P3HB was used, the Mw decreased drastically during early stages of cultivation. These results show that manipulating the P3HB content of the inoculum is possible to produce biopolymers with a suitable Mw. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Adrenal insufficiency is prevalent in HbE/β-thalassaemia paediatric patients irrespective of their clinical severity and transfusion requirement.

    PubMed

    Nakavachara, Pairunyar; Viprakasit, Vip

    2013-12-01

    Transfusion dependency is known to cause endocrinopathies in patients with thalassaemia such as adrenal insufficiency, because transfusion-related iron overload is injurious to endocrine organs. Children with HbE/ß-thalassaemia vary greatly in red cell transfusion requirement and some are transfusion dependent (TD), whereas others are nontransfusion dependent (NTD). Because iron overload is thought to be the primary cause of adrenal insufficiency, TD children with HbE/ß-thalassaemia are considered likely candidates for the development of adrenal insufficiency, while the adrenal function of NTD children is generally considered to be normal. As yet, the prevalence of adrenal insufficiency among children with NTD HbE/β-thalassaemia is not known. The present study was performed to (i) assess the prevalence of adrenal insufficiency in children with both TD and NTD HbE/β-thalassaemia and to evaluate whether there is any difference in the prevalence of adrenal insufficiency between both groups and (ii) determine the type of adrenal insufficiency (primary or secondary). We investigated the prevalence of adrenal insufficiency among TD (n = 42) and NTD (n = 43) children with HbE/β-thalassaemia by assessing morning serum cortisol levels, and we distinguished between primary and secondary adrenal insufficiency by assessing the cortisol responses following the 1- and 250-μg ACTH stimulation tests. The prevalence of adrenal insufficiency among TD and NTD children with HbE/β-thalassaemia was 50% and 53·5%, respectively. By using the 250-μg ACTH stimulation test, at least 39% and 23·5% were diagnosed with adrenal gland hypofunction in TD and NTD children, respectively. This is the first study to show that adrenal insufficiency is common among all children with HbE/β-thalassaemia, irrespective of their transfusion history or requirement. Our findings have important implications for the clinical management of these children. © 2013 John Wiley & Sons Ltd.

  14. 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.

  15. 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'.

  16. Both high and low HbA1c predict incident heart failure in type 2 diabetes mellitus.

    PubMed

    Parry, Helen M; Deshmukh, Harshal; Levin, Daniel; Van Zuydam, Natalie; Elder, Douglas H J; Morris, Andrew D; Struthers, Allan D; Palmer, Colin N A; Doney, Alex S F; Lang, Chim C

    2015-03-01

    Type 2 diabetes mellitus is an independent risk factor for heart failure development, but the relationship between incident heart failure and antecedent glycemia has not been evaluated. The Genetics of Diabetes Audit and Research in Tayside Study study holds data for 8683 individuals with type 2 diabetes mellitus. Dispensed prescribing, hospital admission data, and echocardiography reports were linked to extract incident heart failure cases from December 1998 to August 2011. All available HbA1c measures until heart failure development or end of study were used to model HbA1c time-dependently. Individuals were observed from study enrolment until heart failure development or end of study. Proportional hazard regression calculated heart failure development risk associated with specific HbA1c ranges accounting for comorbidities associated with heart failure, including blood pressure, body mass index, and coronary artery disease. Seven hundred and one individuals with type 2 diabetes mellitus (8%) developed heart failure during follow up (mean 5.5 years, ±2.8 years). Time-updated analysis with longitudinal HbA1c showed that both HbA1c <6% (hazard ratio =1.60; 95% confidence interval, 1.38-1.86; P value <0.0001) and HbA1c >10% (hazard ratio =1.80; 95% confidence interval, 1.60-2.16; P value <0.0001) were independently associated with the risk of heart failure. Both high and low HbA1c predicted heart failure development in our cohort, forming a U-shaped relationship. © 2015 American Heart Association, Inc.

  17. 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.

  18. Measurement of HbA1c in Gingival Crevicular Blood Using a High Pressure Liquid Chromatography Procedure

    PubMed Central

    Pesce, Michael A.; Strauss, Shiela M.; Rosedale, Mary; Netterwald, Jane; Wang, Hangli

    2016-01-01

    Objectives To validate an ion exchange high-pressure liquid chromatography (HPLC) method for measuring glycated hemoglobin (HbA1c) in gingival crevicular blood (GCB) spotted on filter paper, for use in screening dental patients for diabetes. Methods We collected the GCB specimens for this study from the oral cavities of patients during dental visits, using rigorous strategies to obtain GCB that was as free of debris as possible. The analytical performance of the HPLC method was determined by measuring the precision, linearity, carryover, stability of HbA1c in GCB, and correlation of HbA1c results in GCB specimens with finger-stick blood (FSB) specimens spotted on filter paper. Results The coefficients of variation (CVs) for the inter- and intrarun precision of the method were less than 2.0%. Linearity ranged between 4.2% and 12.4%; carryover was less than 2.0%, and the stability of the specimen was 6 days at 4°C and as many as 14 days at −70°C. Linear regression analysis comparing the HbA1c results in GCB with FSB yielded a correlation coefficient of 0.993, a slope of 0.981, and an intercept of 0.13. The Bland-Altman plot showed no difference in the HbA1c results from the GCB and FSB specimens at normal, prediabetes, and diabetes HbA1c levels. Conclusion We validated an HPLC method for measuring HbA1c in GCB; this method can be used to screen dental patients for diabetes. PMID:26489673

  19. Measurement of HbA1c in Gingival Crevicular Blood Using a High-Pressure Liquid Chromatography Procedure.

    PubMed

    Pesce, Michael A; Strauss, Shiela M; Rosedale, Mary; Netterwald, Jane; Wang, Hangli

    2015-01-01

    To validate an ion exchange high-pressure liquid chromatography (HPLC) method for measuring glycated hemoglobin (HbA1c) in gingival crevicular blood (GCB) spotted on filter paper, for use in screening dental patients for diabetes. We collected the GCB specimens for this study from the oral cavities of patients during dental visits, using rigorous strategies to obtain GCB that was as free of debris as possible. The analytical performance of the HPLC method was determined by measuring the precision, linearity, carryover, stability of HbA1c in GCB, and correlation of HbA1c results in GCB specimens with finger-stick blood (FSB) specimens spotted on filter paper. The coefficients of variation (CVs) for the inter- and intrarun precision of the method were less than 2.0%. Linearity ranged between 4.2% and 12.4%; carryover was less than 2.0%, and the stability of the specimen was 6 days at 4°C and as many as 14 days at -70°C. Linear regression analysis comparing the HbA1c results in GCB with FSB yielded a correlation coefficient of 0.993, a slope of 0.981, and an intercept of 0.13. The Bland-Altman plot showed no difference in the HbA1c results from the GCB and FSB specimens at normal, prediabetes, and diabetes HbA1c levels. We validated an HPLC method for measuring HbA1c in GCB; this method can be used to screen dental patients for diabetes. Copyright© by the American Society for Clinical Pathology (ASCP).

  20. 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.

  1. Ethnicity modifies the relation between fasting plasma glucose and HbA1c in Indians, Malays and Chinese.

    PubMed

    Venkataraman, K; Kao, S L; Thai, A C; Salim, A; Lee, J J M; Heng, D; Tai, E S; Khoo, E Y H

    2012-07-01

    To study whether HbA(1c) , and its relationship with fasting plasma glucose, was significantly different among Chinese, Malays and Indians in Singapore. A sample of 3895 individuals without known diabetes underwent detailed interview and health examination, including anthropometric and biochemical evaluation, between 2004 and 2007. Pearson's correlation, analysis of variance and multiple linear regression analyses were used to examine the influence of ethnicity on HbA(1c) . As fasting plasma glucose increased, HbA(1c) increased more in Malays and Indians compared with Chinese after adjustment for age, gender, waist circumference, serum cholesterol, serum triglyceride and homeostasis model assessment of insulin resistance (P-interaction < 0.001). This translates to an HbA(1c) difference of 1.1 mmol/mol (0.1%, Indians vs. Chinese), and 0.9 mmol/mol (0.08%, Malays vs. Chinese) at fasting plasma glucose 5.6 mmol/l (the American Diabetes Association criterion for impaired fasting glycaemia); and 2.1 mmol/mol (0.19%, Indians vs. Chinese) and 2.6 mmol/mol (0.24%, Malays vs. Chinese) at fasting plasma glucose 7.0 mmol/l, the diagnostic criterion for diabetes mellitus. Using HbA(1c) in place of fasting plasma glucose will reclassify different proportions of the population in different ethnic groups. This may have implications in interpretation of HbA(1c) results across ethnic groups and the use of HbA(1c) for diagnosing diabetes mellitus. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.

  2. 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.

  3. CNTO 530 Increases Expression of HbA and HbF in Murine Models of β-Thalassemia and Sickle Cell Anemia

    PubMed Central

    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. PMID:23157711

  4. 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

  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. 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

  7. Simple diagnosis of HbA1c using the dual-plasmonic platform integrated with LSPR and SERS

    NASA Astrophysics Data System (ADS)

    Heo, Nam Su; Kwak, Cheol Hwan; Lee, Hoomin; Kim, Dongjoo; Lee, Sunmook; Kim, Gi-bum; Kwon, Soonjo; Kim, Woo Sik; Huh, Yun Suk

    2017-07-01

    A plasmonic active chip was designed with a transparent polymer film self-assembled with gold nanoparticles (AuNPs). In this study, we demonstrated the feasibility and sensitivity of biosensors by employing a plasmonic resonance technique. AuNPs are widely used as biosensing probes because they facilitate stable immobilization of biomolecules. Transparent polymer film facilitated measurement of changes in absorbance via transmitted light and analysis of Raman scattering via scattered light. The cysteine rich protein G and anti-HbA1c were sequentially conjugated to self-assembled AuNPs on the transparent polymer film to detect a target protein. HbA1c, which is used as an indicator for diabetes diagnosis, was selected for target protein detection. We confirmed the linearly increased absorbance values with increasing HbA1c level (3.19-14.0%) by LSPR detection. We also verified the linear increase in SERS intensity as the concentration of anti-Hb increased from 10 ng mL-1 to 1 μg mL-1 by analyzing the SERS spectra of Cy3 labeled anti-Hb added substrates.

  8. 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.

  9. 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.

  10. National Survey on Internal Quality Control for HbA(1c) Analytical Instruments in 331 Hospital Laboratories of China.

    PubMed

    Zeng, Rong; Wang, Wei; Zhao, Haijian; Fei, Yang; Wang, Zhiguo

    2015-01-01

    The narrow gap of HbA1 value of mass fraction between "normal" (< 6.0%) and "diabetes" (≥ 6.5%) necessitates tight control of inter-assay standardization, assay precision, and trueness. This survey was initiated to obtain knowledge of the current situation of internal quality control (IQC) practice for HbA(1c) in China and find out the most appropriate quality specifications. Data of IQC for HbA(1c) in 331 institutions participating in the national proficiency testing (PT) programs in China were evaluated using four levels of quality specifications, and the percentages of laboratories meeting the quality requirement were calculated to find out the most appropriate quality specifications for control materials of HbA(1c) in China. The IQC data varied vastly among 331 clinical laboratories in China. The measurement of control materials covered a wide range from 4.52% to 12.24% (inter-quartile range) and there were significant differences among the CVs of different methods, including LPLC, CE-HPLC, AC-HPLC, immunoturbidimetry, and others. Among the four main methods, CE-HPLC and AC-HPLC achieved a better precision. As we can see, the performance of laboratories for HbA(1c) has yet to be improved. Clinical laboratories in China should improve their performance with a stricter imprecision criteria.

  11. Hb Cibeles [α2 CD25(B6) (Gly → Asp)]: a novel alpha chain variant causing alpha-thalassemia.

    PubMed

    de la Fuente-Gonzalo, Félix; Nieto, Jorge M; Vinuesa, Lara; Sevilla, Julián; Díaz-Mediavilla, Joaquín; Villegas, Ana; González, Fernando A; Ropero, Paloma

    2014-12-01

    Thalassemias are the most frequent monogenic disorders around the world and are a serious health problem in areas with a high incidence. Thalassemias are particularly frequent in Mediterranean countries, the Middle East, Africa, the Indian subcontinent, and in the Southeast Asia. Of these, α-thalassemia is inherited as an autosomal recessive disorder. α-thalassemias are due to a deficiency or absence of hemoglobin (Hb) α-chain synthesis and are characterized by microcytic and hypochromic cells anemia and a clinical phenotype varying from nearly asymptomatic to a lethal hemolytic anemia. Compound heterozygotes and some homozygotes have a moderate to severe form of α-thalassemia called HbH disease. Hb Bart's hydrops fetalis is a lethal form in which no α-globin chain is synthesized. In this study we show a new structural variant of α-chain, Hb Cibeles [alpha 25(B6) Gly → Asp], in heterozygous state, which was undetectable by electrophoretic or chromatographic methods. Hb Cibeles is thus a hyper-unstable hemoglobinopathy. In this new globin chain variant, an apolar amino acid is replaced by a negatively charged amino acid. This change may be responsible for the molecular hyper-instability similar to the mutation in the adjacent residues.

  12. Prevention of Hb Bart's (γ4) Disease Associated with the - -(THAI) α(0)-Thalassemia Deletion in Mainland China.

    PubMed

    Li, Dong-Zhi; Li, Yan; Li, Jian; Li, Shu-Chen; Li, Ru

    2015-01-01

    α-Thalassemia (α-thal) is a common inherited disease in southern China. The severest form is Hb Bart's (γ4) disease, in which the affected fetuses almost always die in utero or shortly after birth, and the mothers are at high risk for severe morbidity. The most common type of α(0)-thalassemia (α(0)-thal) in southern China is Southeast Asian (- -(SEA)) deletion. Occasionally, Hb Bart's disease, caused by a compound heterozygosity for the - -(SEA) and - -(THAI) α(0)-thal deletions, can also be encountered. In this study, we report our experience with the prevention of Hb Bart's disease associated with the - -(THAI) α(0)-thal deletion. A total of 385 couples at risk for Hb Bart's disease, including seven who tested positive for the - -(SEA) deletion in one partner and the - -(THAI) deletion in the other, were found. Different prenatal procedures were offered, depending on the gestational age at presentation. Sixty-six affected fetuses were diagnosed prenatally; among these, two cases of Hb Bart's disease were compound heterozygotes for the - -(SEA) and - -(THAI) deletions. All affected pregnancies were terminated in time. We also presented a diagnostic protocol for identification of α(0)-thal trait that can reduce the number of samples for detection of the - -(THAI) deletion.

  13. 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.

  14. 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. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Chronic cerebral hypoperfusion-induced impairment of Aβ clearance requires HB-EGF-dependent sequential activation of HIF1α and MMP9.

    PubMed

    Ashok, Anushruti; Rai, Nagendra Kumar; Raza, Waseem; Pandey, Rukmani; Bandyopadhyay, Sanghamitra

    2016-11-01

    Chronic cerebral hypoperfusion (CCH) manifests Alzheimer's Disease (AD) neuropathology, marked by increased amyloid beta (Aβ). Besides, hypoxia stimulates Heparin-binding EGF-like growth factor (HB-EGF) mRNA expression in the hippocampus. However, involvement of HB-EGF in CCH-induced Aβ pathology remains unidentified. Here, using Bilateral Common Carotid Artery Occlusion mouse model, we explored the mechanism of HB-EGF regulated Aβ induction in CCH. We found that HB-EGF inhibition suppressed, while exogenous-HB-EGF triggered hippocampal Aβ, proving HB-EGF-dependent Aβ increase. We also detected that HB-EGF affected the expression of primary Aβ transporters, receptor for advanced glycation end-products (RAGE) and lipoprotein receptor-related protein-1 (LRP-1), indicating impaired Aβ clearance across the blood-brain barrier (BBB). An HB-EGF-dependent loss in BBB integrity supported impaired Aβ clearance. The effect of HB-EGF on Amyloid Precursor Protein pathway was relatively insignificant, suggesting a lesser effect on Aβ generation. Delving into BBB disruption mechanism demonstrated HB-EGF-mediated stimulation of Matrix metalloprotease-9 (MMP9), which affected BBB via HB-EGF-ectodomain shedding and epidermal growth factor receptor activation. Examining the intersection of HB-EGF-regulated pathway and hypoxia revealed HB-EGF-dependent increase in transcription factor, Hypoxia-inducible factor-1alpha (HIF1α). Further, via binding to hypoxia-responsive elements in MMP9 gene, HIF1α stimulated MMP9 expression, and therefore appeared as a prominent intermediary in HB-EGF-induced BBB damage. Overall, our study reveals the essential role of HB-EGF in triggering CCH-mediated Aβ accumulation. The proposed mechanism involves an HB-EGF-dependent HIF1α increase, generating MMP9 that stimulates soluble-HB-EGF/EGFR-induced BBB disintegration. Consequently, CCH-mediated hippocampal RAGE and LRP-1 deregulation together with BBB damage impair Aβ transport and clearance

  16. HbA1c values calculated from blood glucose levels using truncated Fourier series and implementation in standard SQL database language.

    PubMed

    Temsch, W; Luger, A; Riedl, M

    2008-01-01

    This article presents a mathematical model to calculate HbA1c values based on self-measured blood glucose and past HbA1c levels, thereby enabling patients to monitor diabetes therapy between scheduled checkups. This method could help physicians to make treatment decisions if implemented in a system where glucose data are transferred to a remote server. The method, however, cannot replace HbA1c measurements; past HbA1c values are needed to gauge the method. The mathematical model of HbA1c formation was developed based on biochemical principles. Unlike an existing HbA1c formula, the new model respects the decreasing contribution of older glucose levels to current HbA1c values. About 12 standard SQL statements embedded in a php program were used to perform Fourier transform. Regression analysis was used to gauge results with previous HbA1c values. The method can be readily implemented in any SQL database. The predicted HbA1c values thus obtained were in accordance with measured values. They also matched the results of the HbA1c formula in the elevated range. By contrast, the formula was too "optimistic" in the range of better glycemic control. Individual analysis of two subjects improved the accuracy of values and reflected the bias introduced by different glucometers and individual measurement habits.

  17. 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

  18. Factors associated with reaching or not reaching target HbA1c after initiation of basal or premixed insulin in patients with type 2 diabetes.

    PubMed

    Scheen, A J; Schmitt, H; Jiang, H H; Ivanyi, T

    2017-02-01

    To evaluate factors associated with reaching or not reaching target glycated haemoglobin (HbA1c) levels by analysing the respective contributions of fasting hyperglycaemia (FHG), also referred to as basal hyperglycaemia, vs postprandial hyperglycaemia (PHG) before and after initiation of a basal or premixed insulin regimen in patients with type 2 diabetes. This post-hoc analysis of insulin-naïve patients in the DURABLE study randomised to receive either insulin glargine or insulin lispro mix 25 evaluated the percentages of patients achieving a target HbA1c of <7.0% (<53mmol/mol) per baseline HbA1c quartiles, and the effect of each insulin regimen on the relative contributions of PHG and FHG to overall hyperglycaemia. Patients had comparable demographic characteristics and similar HbA1c and FHG values at baseline in each HbA1c quartile regardless of whether they reached the target HbA1c. The higher the HbA1c quartile, the greater was the decrease in HbA1c, but also the smaller the percentage of patients achieving the target HbA1c. HbA1c and FHG decreased more in patients reaching the target, resulting in significantly lower values at endpoint in all baseline HbA1c quartiles with either insulin treatment. Patients not achieving the target HbA1c had slightly higher insulin doses, but lower total hypoglycaemia rates. Smaller decreases in FHG were associated with not reaching the target HbA1c, suggesting a need to increase basal or premixed insulin doses to achieve targeted fasting plasma glucose and improve patient response before introducing more intensive prandial insulin regimens. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  19. 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.

  20. Divergence between HbA1c and fasting glucose through childhood: implications for diagnosis of impaired fasting glucose (Early Bird 52).

    PubMed

    Hosking, Joanne; Metcalf, Brad S; Jeffery, Alison N; Streeter, Adam J; Voss, Linda D; Wilkin, Terence J

    2014-05-01

    An HbA1c threshold of ≥ 6.5% has recently been adopted for the diagnosis of diabetes in adults, and of ≥ 5.7% to identify adults at risk. Little,however, is known of HbA1c's behaviour or diagnostic value in youth. Our aim was to describe the course of HbA1c during childhood, and its association with fasting glucose. HbA1c and glucose were measured every year in a cohort of 326 healthy children (162 boys) from 5 to 15 years. Mixed effects modelling was used to establish the determinants of HbA1c and its development over time. ROC analysis was used to determine the diagnostic value of HbA1c in the 55 individuals who showed impaired fasting glucose(IFG – glucose ≥ 5.6 mmol/L). Glucose rose progressively from 4.3 mmol/L at 5 years to 5.1 mmol/Lat 15 years, and although there were positive associations between HbA1c and glucose, from 10 to 13 years, HbA1c fell while glucose continued to rise. IFG developed in 55 children, but HbA1c exceeded 5.7% in only 16 of them. The maximum area under the ROC curve was 0.71 at the age of 14 (p<0.001), and the sensitivity and specificity were optimal at 50 and 80% respectively,corresponding to HbA1c of 5.4%. Although HbA1c retains a positive association with glucose throughout childhood, it is weak, and their trends diverge from 10 years,suggesting that factors other than glycaemia systematically influence the variance of HbA1c in youth. These findings therefore limit the interpretation of HbA1c for the diagnosis of IFG during childhood.

  1. Catalysis of Dioxygen Reduction by Thermus thermophilus Strain HB27 Laccase on Ketjen Black Electrodes

    PubMed Central

    Agbo, Peter; Heath, James R.

    2012-01-01

    We present electrochemical analyses of the catalysis of dioxygen reduction by Thermus thermophilus strain HB27 laccase on ketjen black substrates. Our cathodes reliably produce 0.56 mA cm−2 at 0.0 V vs. Ag|AgCl reference at 30 °C in air-saturated buffer, under conditions of non-limiting O2 flux. We report the electrochemical activity of this laccase as a function of temperature, pH, time, and the efficiency of its conversion of dioxygen to water. We have measured the surface concentration of electrochemically active species, permitting the extraction of electron transfer rates at the enzyme-electrode interface: 1 s−1 for this process at zero driving force at 30 °C and a limiting rate of 23 s−1 at 240 mV overpotential at 50 °C. PMID:23163614

  2. Quality of HbA1c Measurement in the Practice

    PubMed Central

    Freckmann, Guido

    2015-01-01

    Hemoglobin A1c (HbA1c) measurement has come to be a cornerstone in modern diabetes therapy. However, the methodological aspects of this type of measurement have been given little attention lately due to its position as an established method of choice. Nevertheless, quite a number of issues face practical application, such as clinically relevant differences between different measurement methods—both lab-based and point-of-care (POCT) systems will show better or worse diabetes management results after switching methods; and there are a number of possible reasons that need to be known and observed in practice. The aim of this review is to draw attention to these problems from a German point of view and provide suggestions for appropriate measures to improve the situation. PMID:25691655

  3. Rapid and sensitive amino-acid sequencing of cloning Thermus thermophilus HB8 ferredoxin by proteomics.

    PubMed

    Kaneko, Maki; Masui, Ryoji; Ake, Kojiro; Kousumi, Yukihide; Kuramitsu, Seiki; Yamaguchi, Minoru; Kuyama, Hiroki; Ando, Eiji; Norioka, Shigemi; Nakazawa, Takashi; Okamura, Taka-Aki; Yamamoto, Hitoshi; Ueyama, Norikazu

    2004-01-01

    Recombinant holo Thermus thermophilus [7Fe-8S] ferredoxin was synthesized by cloning from Thermus thermophilus HB8 gene. A specific sequence (Pro-His-Val-Ile) at the N-terminus of the recombinant ferredoxin was determined by a rapid and highly sensitive mass spectral method using a novel Ru(II) Edman reagent, [(tpy)Ru(tpy-C6H4-NCS)](PF6)2 (tpy=terpyridine). The formation of the recombinant holoTtFd was established by the characteristic absorptions and CD extrema as [7Fe-8S] ferredoxin. The catalytic electron-transfer reactivity of the [7Fe-8S] ferredoxin between ferredoxin-NADP+ reductase and cytochrome c was recognized.

  4. 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.

  5. 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.

  6. 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].

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. Establishment of a Cell Line From Conjunctival Squamous Cell Carcinoma: PeCa-UkHb-01.

    PubMed

    Thomasen, Henning; Müller, Bettina; Poetsch, Micaela; Steuhl, Klaus-Peter; Meller, Daniel

    2015-07-01

    Until now, no epithelial cell line from conjunctival squamous cell carcinoma (SCC), to our knowledge, has existed; therefore, the establishment of a model cell line would be a useful tool for further studies. In particular, the phenotypic and molecular characterization in comparison to other SCC cells is of high interest because this would enable the development of new treatment options for clinical application in ophthalmic oncology. Epithelial cells were isolated from a bulbar conjunctiva SCC obtained from a 74-year-old male, harvested by stepwise trypsinization and named PeCa-UkHb-01. Cell doubling and the number of passages were determined. Short tandem repeats (STR) and karyotype analyses were performed. Semiquantitative real-time PCR and immunocytochemical fluorescence staining were carried out to detect tumor and epithelial cell markers. The cells had an epithelial and conjunctival phenotype. They grew above passage number 50 in a doubling time at approximately 34.5 hours. Short tandem repeat analyses confirmed the cell origin, although loss of heterozygosity occurred. Karyotype analyses revealed a heterogeneous composition of the cell culture and the karyogram itself showed aberrations and changes in the chromosome numbers. Real-time PCR and immunocytochemical fluorescence staining revealed the expression of the stem cell markers such as ABCG2, p63, OCT4, c-MYC, and SOX2 as well as the conjunctival cytokeratin K19. PeCa-UkHb-01 cells fulfill the criteria of a cell line. They display characteristics of ocular carcinoma cells and therefore the presented cell line might serve for further basic research in ophthalmic oncology.

  12. Medication Adherence and Racial Differences in HbA1c Control

    PubMed Central

    Adams, Alyce S.; Trinacty, Connie Mah; Zhang, Fang; Kleinman, Ken; Grant, Richard W.; Meigs, James B.; Soumerai, Stephen B.; Ross-Degnan, Dennis

    2008-01-01

    Objective The purpose of this study was to examine medication adherence and other self-management practices as potential determinants of higher glycemic risk among black relative to white patients. Research Design and Methods We used a retrospective, longitudinal repeated measures design to model the contribution of medication adherence to black-white differences in HbA1c among Type 2 diabetes patients at a large multi-specialty group practice. We identified 1,806 adult (age 18+ at diagnosis) patients (black=467, white=1339) newly initiated on oral hypoglycemic therapy between 01/01/94 and 12/31/00. Race was identified using an electronic medical record and patient self-reports. Baseline was defined as the 13-months preceding and including the month of therapy initiation. All patients were required to have at least 12 months of follow up. Results At initiation of therapy, black patients had higher average hemoglobin A1c values compared to whites 9.8 vs. 8.9, a difference of 0.88 (p<0.0001). Blacks had lower average medication adherence during the first year on therapy [72% vs. 78%; p<0.0001]. While more frequent medication refills were associated with lower average HbA1c values, adjustment for adherence did not eliminate the black-white gap. Conclusions We found persistent racial differences in hemoglobin A1c that were not explained by differences in medication adherence. Our findings suggest that targeting medication adherence alone is unlikely to reduce disparities in glycemic control in this setting. Further research is needed to explore possible genetic and environmental determinants of higher A1c among blacks at diagnosis, which may represent a critical period for more intensive intervention. PMID:18235050

  13. 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.

  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. Micro-regional mapping of HbO[sub 2] saturations and blood flow following nicotinamide administration

    SciTech Connect

    Fenton, B.M.; Boyce, D.J. )

    1994-06-15

    Although nicotinamide administration has increased the radiosensitivity of experimental tumors, there is a scarcity of data detailing the underlying physiological mechanisms. The current study presents a method for quantifying both microregional distributions of intravascular HbO[sub 2] saturations and the presence or absence of blood flow in adjacent frozen tumor sections. Two murine tumor cell lines, KHT and SCCVII, were implanted and quick-frozen without the use of anesthetics. Nicotinamide was administered IP 1 h prior to freezing, and a fluorescent dye that preferentially stains cells adjacent to blood vessels was injected IV 1 min prior to freezing. To visualize the presence or absence of blood flow, six micron sections were first cut using a cryostat. The remaining frozen tumor block was then analyzed cryospectrophotometrically to determine intravascular HbO[sub 2] levels. While KHT HbO[sub 2] levels increased somewhat predictably following nicotinamide, the response in SCCVII tumors varied with distance from the tumor surface. Near the periphery, SCCVII HbO[sub 2] levels increased, but nearer the tumor center, HbO[sub 2] levels actually decreased. Perfused blood vessels were uniformly distributed throughout the tumor volume except in regions of necrosis. Even vessels containing no measurable oxygen remained perfused, as evidenced by the presence of the fluorescent marker. These results demonstrate that nicotinamide raises intravascular HbO[sub 2] saturations in both KHT and SCCVII tumors. This increase in oxygen delivery is not evenly distributed throughout the tumor volume in spite of a uniform distribution of perfused blood vessels. Blood flow in a substantial proportion of these vessels is most likely not sufficiently rapid to serve a functional purpose in terms of oxygen supply to the surrounding tumor tissue. 15 refs., 4 figs.

  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. HbA1c and Gestational Weight Gain Are Factors that Influence Neonatal Outcome in Mothers with Gestational Diabetes.

    PubMed

    Barquiel, Beatriz; Herranz, Lucrecia; Hillman, Natalia; Burgos, Ma Ángeles; Grande, Cristina; Tukia, Keleni M; Bartha, José Luis; Pallardo, Luis Felipe

    2016-06-01

    Maternal glucose and weight gain are related to neonatal outcome in women with gestational diabetes mellitus (GDM). The aim of this study was to explore the influence of average third-trimester HbA1c and excess gestational weight gain on GDM neonatal complications. This observational study included 2037 Spanish singleton pregnant women with GDM followed in our Diabetes and Pregnancy Unit. The maternal HbA1c level was measured monthly from GDM diagnosis to delivery. Women were compared by average HbA1c level and weight gain categorized into ≤ or > the current Institute of Medicine (IOM) recommendations for body mass index. The differential effects of these factors on large-for-gestational-age birth weight and a composite of neonatal complications were assessed. Women with an average third-trimester HbA1c ≥5.0% (n = 1319) gave birth to 7.3% versus 3.8% (p = 0.005) of large-for-gestational-age neonates and 22.0% versus 16.0% (p = 0.006) of neonates with complications. Women with excess gestational weight gain (n = 299) delivered 12.5% versus 5.2% (p < 0.001) of large-for-gestational-age neonates and 24.7% versus 19.0% (p = 0.022) of neonates with complications. In an adjusted multiple logistic regression analysis among mothers exposed to the respective risk factors, ∼47% and 52% of large-for-gestational-age neonates and 32% and 37% of neonatal complications were potentially preventable by attaining an average third-trimester HbA1c level <5.0% and optimizing gestational weight gain. Average third-trimester HbA1c level ≥5% and gestational weight gain above the IOM recommendation are relevant risk factors for neonatal complications in mothers with gestational diabetes.

  18. 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.

  19. Co-inheritance of compound heterozygous Hb Constant Spring and a single -alpha(3.7) gene deletion with heterozygous deltabeta thalassaemia: a diagnostic challenge.

    PubMed

    Azma, Raja Zahratul; Othman, Ainoon; Azman, Norazlina; Alauddin, Hafiza; Ithnin, Azlin; Yusof, Nurasyikin; Razak, Noor Farisah; Sardi, Nor Hidayati; Hussin, Noor Hamidah

    2012-06-01

    Haemoglobin Constant Spring (Hb CS) mutation and single gene deletions are common underlying genetic abnormalities for alpha thalassaemias. Co-inheritance of deletional and non-deletional alpha (alpha) thalassaemias may result in various thalassaemia syndromes. Concomitant co-inheritance with beta (beta) and delta (delta) gene abnormalities would result in improved clinical phenotype. We report here a 33-year-old male patient who was admitted with dengue haemorrhagic fever, with a background history of Grave's disease, incidentally noted to have mild hypochromic microcytic red cell indices. Physical examination revealed no thalassaemic features or hepatosplenomegaly. His full blood picture showed hypochromic microcytic red cells with normal haemoglobin (Hb) level. Quantitation of Hb using high performance liquid chromatography (HPLC) and capillary electrophoresis (CE) revealed raised Hb F, normal Hb A2 and Hb A levels. There was also small peak of Hb CS noted in CE. H inclusions was negative. Kleihauer test was positive with heterocellular distribution of Hb F among the red cells. DNA analysis for alpha globin gene mutations showed a single -alpha(-3.7) deletion and Hb CS mutation. These findings were suggestive of compound heterozygosity of Hb CS and a single -alpha(-3.7) deletion with a concomitant heterozygous deltabeta thalassaemia. Co-inheritance of Hb CS and a single -alpha(-3.7) deletion is expected to result at the very least in a clinical phenotype similar to that of two alpha genes deletion. However we demonstrate here a phenotypic modification of alpha thalassemia presumptively as a result of co-inheritance with deltabeta chain abnormality as suggested by the high Hb F level.

  20. A Novel Mutation of the α2-Globin Gene Causing α(+)-Thalassemia: Hb Nanning (HBA2: c.369_370delinsGA).

    PubMed

    Chen, Biyan; Lin, Li; Yi, Shang; Chen, Qiuli; Wei, Hongwei; Li, Guojian; Zheng, Chenguang; He, Sheng; Qiu, XiaoXia

    2017-01-01

    We report a novel mutation on the α2-globin gene, Hb Nanning (HBA2:c.369_370delinsGA) detected in a Chinese family. This mutation gives rise to a previously undescribed hemoglobin (Hb) variant that was undetectable by various separation techniques. Both carriers of the mutation have mean corpuscular volume (MCV) and mean corpuscular Hb (MCH) values that are below normal, as would be predicted for an α(+)-thalassemia (α(+)-thal) patient.

  1. Neonatal cyanosis due to a novel fetal hemoglobin: Hb F-Circleville [Ggamma63(E7)His-->Leu, CAT>CTT].

    PubMed

    Dainer, Erin; Shell, Richard; Miller, Randy; Atkin, Joan F; Pastore, Matt; Kutlar, Abdullah; Zhuang, Lina; Holley, Leslie; Davis, Debra H; Kutlar, Ferdane

    2008-01-01

    Neonatal cyanosis can result from a multitude of acquired and inherited causes. Cyanosis resulting from fetal M hemoglobin (Hb) variants is very rare. Only two (G)gamma variants causing methemoglobinemia and cyanosis in the newborn have been reported to date. Here we describe a novel fetal Hb variant, Hb F-Circleville [Ggamma63(E7)His-->Leu], associated with methemoglobinemia and cyanosis in the newborn. The patient's sister also had neonatal cyanosis at birth.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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.…

  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

    ... permit are needed. No effects on the aquatic or terrestrial habitat in the vicinity or the plant, or to... 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, South...

  8. 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.

  9. 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.

  10. 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.

  11. High copy and stable expression of the xylanase XynHB in Saccharomyces cerevisiae by rDNA-mediated integration.

    PubMed

    Fang, Cheng; Wang, Qinhong; Selvaraj, Jonathan Nimal; Zhou, Yuling; Ma, Lixin; Zhang, Guimin; Ma, Yanhe

    2017-08-18

    Xylanase is a widely-used additive in baking industry for enhancing dough and bread quality. Several xylanases used in baking industry were expressed in different systems, but their expression in antibiotic free vector system is highly essential and safe. In the present study, an alternative rDNA-mediated technology was developed to increase the copy number of target gene by integrating it into Saccharomyces cerevisiae genome. A xylanase-encoding gene xynHB from Bacillus sp. was cloned into pHBM367H and integrated into S. cerevisiae genome through rDNA-mediated recombination. Exogenous XynHB expressed by recombinant S. cerevisiae strain A13 exhibited higher degradation activity towards xylan than other transformants. The real-time PCR analysis on A13 genome revealed the presence of 13.64 copies of xynHB gene. Though no antibiotics have been used, the genetic stability and the xylanase activity of xynHB remained stable up to 1,011 generations of cultivation. S. cerevisiae strain A13 expressing xylanase reduced the required kneading time and increased the height and diameter of the dough size, which would be safe and effective in baking industry as no antibiotics-resistance risk. The new effective rDNA-mediated technology without using antibiotics here provides a way to clone other food related industrial enzymes for applications.

  12. 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.

  13. 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.

  14. Perceived weight discrimination amplifies the link between central adiposity and nondiabetic glycemic control (HbA1c).

    PubMed

    Tsenkova, Vera K; Carr, Deborah; Schoeller, Dale A; Ryff, Carol D

    2011-04-01

    While the preclinical development of type 2 diabetes is partly explained by obesity and central adiposity, psychosocial research has shown that chronic stressors such as discrimination have health consequences as well. We investigated the extent to which the well-established effects of obesity and central adiposity on nondiabetic glycemic control (indexed by HbA(1c)) were moderated by a targeted psychosocial stressor linked to weight: perceived weight discrimination. The data came from the nondiabetic subsample (n = 938) of the Midlife in the United States (MIDUS II) survey. Body mass index (BMI), waist-to-hip ratio, and waist circumference were linked to significantly higher HbA(1c) (p < 0.001). Multivariate-adjusted models showed that weight discrimination exacerbated the effects of waist-to-hip ratio on HbA(1c) ( p < 0.05), such that people who had higher waist-to-hip ratios and reported weight discrimination had the highest HbA(1c) levels. Understanding how biological and psychosocial factors interact at nondiabetic levels to increase vulnerability could have important implications for public health and education strategies. Effective strategies may include targeting sources of discrimination rather than solely targeting the health behaviors and practices of overweight and obese persons.

  15. Evaluation of a Methodology for Estimating HbA1c Value by a New Glucose Meter.

    PubMed

    Sieber, Jochen; Flacke, Frank; Dumais, Bonnie; Peters, Casey C; Mallery, Erin B; Taylor, Liz

    2015-05-22

    Accuracy/robustness of HbA1c estimation (eA1c) with an algorithm built into the MyStar Extra blood glucose (BG) meter has been demonstrated by in silico testing. We evaluated the performance and use of eA1c in a clinical setting. Subjects took the BG meter home for 4 months to obtain eA1c in this open-label, single-center study. Laboratory HbA1c values were obtained approximately every 2 weeks and the corresponding eA1c documented. Subjects completed a questionnaire at study end (NCT01885546). There were 133 enrolled subjects (mean [SD] age 60.0 [15.0] years, 69 males, 104 with diabetes, HbA1c 7.0% [1.4]). A total of 1008 pairs of eA1c and laboratory HbA1c values were available. In subjects with diabetes, 97.5% of the eA1c results fell within ± 20% of the laboratory HbA1c, 95.0% within ± 18%, and 90.7% within ± 15%. When results were limited to the reportable HbA1c range of ≥ 6 to ≤ 10%, 99.3% of eA1c values fell within ± 20% of the laboratory HbA1c, 98.5% within ± 18%, and 96.2% within ± 15% Most subjects agreed/strongly agreed that the eA1c section in the user guide and flash cards was easy to follow (72%), they would use the system to track their eA1c (70%), they found the eA1c tool helpful (79%), and the tool may motivate them to manage their diabetes better (83%). Accuracy of the eA1c feature in this clinical setting was similar to the performance in silico. The majority of subjects found this tool helpful and agreed it may motivate to manage their diabetes better. © 2015 Diabetes Technology Society.

  16. 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

  17. 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

  18. 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

  19. Mechanical stretch promotes fetal type II epithelial cell differentiation via shedding of HB-EGF and TGF-α

    PubMed Central

    Wang, Yulian; Maciejewski, Benjamin S; Soto-Reyes, Dariana; Lee, Hyeon-Soo; Warburton, David; Sanchez-Esteban, Juan

    2009-01-01

    The mechanisms by which mechanical forces promote fetal lung development are not fully understood. Here, we investigated differentiation of fetal type II epithelial cells via the epidermal growth factor receptor (EGFR) in response to mechanical strain. First, we showed that incubation of embryonic day (E) 19 fetal type II cells with recombinant heparin-binding EGF-like growth factor (HB-EGF) or transforming growth factor (TGF)-α, but not with amphiregulin (AR), betacellulin (BTC) or epiregulin (EPR), increased fetal type II cell differentiation, as measured by surfactant protein B/C mRNA and protein levels. Next, we demonstrated that 5% cyclic stretch of E19 monolayers transfected with plasmid encoding alkaline phosphatase (AP)-tagged ligands shed mature HB-EGF and TGF-α into the supernatant and promoted type II cell differentiation. Release of these ligands was also observed in E19 cells subjected to higher degrees of cyclic strain, but not in cells exposed to continuous stretch. Interestingly, the addition of fibroblasts to type II cell cultures did not enhance release of HB-EGF. Whereas HB-EGF shedding was also detected in E18 cells exposed to 5% cyclic stretch, release of this ligand after 2.5% sustained stretch was restricted to cells isolated on E18 of gestation. In addition, mechanical stretch released EGF, AR and BTC. We conclude that mechanical stretch promotes fetal type II cell differentiation via ectodomain shedding of HB-EGF and TGF-α. The magnitude of shedding varied depending on gestational age, ligand, and strain protocol. These studies provide novel mechanistic information potentially relevant to fetal lung development and to mechanical ventilation-induced lung injury. PMID:19237431

  20. NGF and HB-EGF: potential biomarkers that reflect the effects of fesoterodine in patients with overactive bladder syndrome.

    PubMed

    Kim, Soo Rim; Moon, Yeo Jung; Kim, Sei Kwang; Bai, Sang Wook

    2015-01-01

    To determine whether levels of nerve growth factor (NGF) and heparin-binding epidermal growth factor-like growth factor (HB-EGF) can be used to objectively assess overactive bladder syndrome (OAB) treatment outcome and to evaluate the effects of fixed-dose fesoterodine on OAB symptoms. This study included 124 participants (62 patients with OAB and 62 controls) in Severance Hospital between 2010 and 2012. In patients with OAB, 4 mg fesoterodine was administered once daily. Repeated evaluations of putative biomarker levels, urine creatinine (Cr) levels, and questionnaire responses, including the Overactive Bladder Symptom Score (OABSS) and the Overactive Bladder Questionnaire (OAB q), were performed from baseline to 16 weeks. Urinary levels of NGF/Cr (OAB: 1.13±0.9 pg/mg; control: 0.5±0.29 pg/mg) and HB-EGF/Cr (OAB: 8.73±6.55 pg/mg; control: 4.45±2.93 pg/mg) were significantly higher in subjects with OAB than in controls (p<0.001). After 16 weeks of fixed-dose fesoterodine treatment, urinary NGF/Cr levels (baseline: 1.13±0.08 pg/mg; 16 weeks: 0.60±0.4 pg/mg; p=0.02) and HB-EGF/Cr levels significantly decreased (baseline: 8.73±6.55 pg/mg; 16 weeks: 4.72±2.69 pg/mg; p=0.03, respectively). Both the OABSS and OAB q scores improved (p<0.001). However, there were no a statistically significant correlations between these urinary markers and symptomatic scores. Urinary levels of NGF and HB-EGF may be potential biomarkers for evaluating outcome of OAB treatment. Fixed-dose fesoterodine improved OAB symptoms. Future studies are needed to further examine the significance of urinary NGF and HB-EGF levels as therapeutic markers for OAB.

  1. 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.

  2. Antiproliferative activity of monastrol in human adenocarcinoma (MCF-7) and non-tumor (HB4a) breast cells.

    PubMed

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

    2016-12-01

    Monastrol is an allosteric inhibitor of the mitotic kinesin Eg5 that exhibits an antiproliferative effect against several cell lines. We investigated the antiproliferative effect of monastrol on human breast adenocarcinoma cells (MCF-7) and mammary epithelial cells (HB4a, non-tumoral). Monastrol treatment decreased cell viability only in MCF-7 tumor cells. Real-time cell growth kinetic analysis showed a decrease in the proliferation of MCF-7 cells exposed to monastrol, while in the HB4a cells, only a concentration of 100 μM was able to induce this effect. In a cell cycle analysis, exposure of MCF-7 cells to monastrol led to an increased population of cells in both the G1 and G2/M phases. In HB4a cells, the proportion of cells in the G2/M phase was increased. Monastrol led to an increased mitotic index in both cell lines. Monastrol was not able to induce cell death by apoptosis in any of the cell lines studied. Gene expression analysis was performed to measure the mRNA levels of cell cycle genes, DNA damage indicator gene, and apoptotic related genes. Treatment with monastrol induced in MCF-7 cells a 5-fold increase in the mRNA levels of the CDKN1A gene, an inhibitor of CDKs related with cell cycle arrest in response a stress stimulus, and a 2-fold decrease in CDKN1C mRNA levels in HB4a cells. These results provide evidence that monastrol has a greater antiproliferative effect on MCF-7 tumor cells compared with non-tumor HB4a cells; however, no selective is observed.

  3. 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.

  4. Bridging Theory and Experiment to Address Structural Properties of Truncated Haemoglobins: Insights from Thermobifida fusca HbO.

    PubMed

    Howes, Barry D; Boechi, Leonardo; Boffi, Alberto; Estrin, Dario E; Smulevich, Giulietta

    2015-01-01

    In this chapter, we will discuss the paradigmatic case of Thermobifida fusca (Tf-trHb) HbO in its ferrous and ferric states and its behaviour towards a battery of possible ligands. This choice was dictated by the fact that it has been one of the most extensively studied truncated haemoglobins, both in terms of spectroscopic and molecular dynamics studies. Tf-trHb typifies the structural properties of group II trHbs, as the active site is characterized by a highly polar distal environment in which TrpG8, TyrCD1, and TyrB10 provide three potential H-bond donors in the distal cavity capable of stabilizing the incoming ligands. The role of these residues in key topological positions, and their interplay with the iron-bound ligands, has been addressed in studies carried out on the CO, F(-), OH(-), CN(-), and HS(-) adducts formed with the wild-type protein and a combinatorial set of mutants, in which the distal polar residues, TrpG8, TyrCD1, and TyrB10, have been singly, doubly, or triply replaced by a Phe residue. In this context, such a complete analysis provides an excellent benchmark for the investigation of the relationship between protein structure and function, allowing one to translate physicochemical properties of the active site into the observed functional behaviour. Tf-trHb will be compared with other members of the group II trHbs and, more generally, with members of the other trHb subgroups. © 2015 Elsevier Ltd. All rights reserved.

  5. 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.

  6. 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.

  7. The Effect of Prolonged Glucosamine Usage on HbA1c Levels and New-Onset Diabetes Mellitus in Overweight and Obese Middle-Aged Women.

    PubMed

    Gommans, Yvonne M M; Runhaar, Jos; Jacobs, Marloes L; Bierma-Zeinstra, Sita M A

    2017-06-01

    The aim of the present study was to evaluate the effect of a 2.5-year glucosamine sulfate intervention on hemoglobin A1c (HbA1c) levels and the incidence of new-onset diabetes mellitus over 6.5 years in middle-aged women with a body mass index ≥27 kg/m(2). In total, 407 women were randomized into either oral crystalline glucosamine sulfate or placebo. At baseline, 1 year, 2.5 years, and 6.5 years, a blood sample for the HbA1c level was drawn and questionnaires were taken. After 6.5 years there were missing data for some variables, therefore, multiple imputation was used. With the imputed data, a generalized estimating equation was performed to analyze the effect of glucosamine sulfate usage over 6.5 years. Finally, these analyses were rerun for the 2 subgroups of participants with and without high HbA1c level (≥42 mmol/mol) at baseline. There was no significant effect of a 2.5-year glucosamine sulfate intervention on mean HbA1c level or on obtaining a high HbA1c level or new-onset diabetes mellitus over 6.5 years. The subgroup analyses of participants with and without high HbA1c level at baseline were also not statistically significant. However, participants with a high HbA1c level at baseline had higher odds ratios compared with the participants with a normal HbA1c at baseline. There was no effect of glucosamine sulfate on mean HbA1c level nor on obtaining a high HbA1c level or new-onset diabetes mellitus over 6.5 years, especially in participants with a normal HbA1c level at baseline. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. 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.

  9. Targeting hepatic heparin-binding EGF-like growth factor (HB-EGF) induces anti-hyperlipidemia leading to reduction of angiotensin II-induced aneurysm development.

    PubMed

    Kim, Seonwook; Yang, Lihua; Kim, Seongu; Lee, Richard G; Graham, Mark J; Berliner, Judith A; Lusis, Aldons J; Cai, Lei; Temel, Ryan E; Rateri, Debra L; Lee, Sangderk

    2017-01-01

    The upregulated expression of heparin binding EGF-like growth factor (HB-EGF) in the vessel and circulation is associated with risk of cardiovascular disease. In this study, we tested the effects of HB-EGF targeting using HB-EGF-specific antisense oligonucleotide (ASO) on the development of aortic aneurysm in a mouse aneurysm model. Low-density lipoprotein receptor (LDLR) deficient mice (male, 16 weeks of age) were injected with control and HB-EGF ASOs for 10 weeks. To induce aneurysm, the mice were fed a high fat diet (22% fat, 0.2% cholesterol; w/w) at 5 week point of ASO administration and infused with angiotensin II (AngII, 1,000ng/kg/min) for the last 4 weeks of ASO administration. We confirmed that the HB-EGF ASO administration significantly downregulated HB-EGF expression in multiple tissues including the liver. Importantly, the HB-EGF ASO administration significantly suppressed development of aortic aneurysms including thoracic and abdominal types. Interestingly, the HB-EGF ASO administration induced a remarkable anti-hyperlipidemic effect by suppressing very low density lipoprotein (VLDL) level in the blood. Mechanistically, the HB-EGF targeting suppressed hepatic VLDL secretion rate without changing heparin-releasable plasma triglyceride (TG) hydrolytic activity or fecal neutral cholesterol excretion rate. This result suggested that the HB-EGF targeting induced protection against aneurysm development through anti-hyperlipidemic effects. Suppression of hepatic VLDL production process appears to be a key mechanism for the anti-hyperlipidemic effects by the HB-EGF targeting.

  10. Targeting hepatic heparin-binding EGF-like growth factor (HB-EGF) induces anti-hyperlipidemia leading to reduction of angiotensin II-induced aneurysm development

    PubMed Central

    Kim, Seonwook; Yang, Lihua; Kim, Seongu; Lee, Richard G.; Graham, Mark J.; Berliner, Judith A.; Lusis, Aldons J.; Cai, Lei; Temel, Ryan E.; Rateri, Debra L.

    2017-01-01

    Objective The upregulated expression of heparin binding EGF-like growth factor (HB-EGF) in the vessel and circulation is associated with risk of cardiovascular disease. In this study, we tested the effects of HB-EGF targeting using HB-EGF-specific antisense oligonucleotide (ASO) on the development of aortic aneurysm in a mouse aneurysm model. Approach and results Low-density lipoprotein receptor (LDLR) deficient mice (male, 16 weeks of age) were injected with control and HB-EGF ASOs for 10 weeks. To induce aneurysm, the mice were fed a high fat diet (22% fat, 0.2% cholesterol; w/w) at 5 week point of ASO administration and infused with angiotensin II (AngII, 1,000ng/kg/min) for the last 4 weeks of ASO administration. We confirmed that the HB-EGF ASO administration significantly downregulated HB-EGF expression in multiple tissues including the liver. Importantly, the HB-EGF ASO administration significantly suppressed development of aortic aneurysms including thoracic and abdominal types. Interestingly, the HB-EGF ASO administration induced a remarkable anti-hyperlipidemic effect by suppressing very low density lipoprotein (VLDL) level in the blood. Mechanistically, the HB-EGF targeting suppressed hepatic VLDL secretion rate without changing heparin-releasable plasma triglyceride (TG) hydrolytic activity or fecal neutral cholesterol excretion rate. Conclusion This result suggested that the HB-EGF targeting induced protection against aneurysm development through anti-hyperlipidemic effects. Suppression of hepatic VLDL production process appears to be a key mechanism for the anti-hyperlipidemic effects by the HB-EGF targeting. PMID:28792970

  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. Features of glycemic variations in drug naïve type 2 diabetic patients with different HbA1c values.

    PubMed

    Li, Feng-Fei; Liu, Bing-Li; Yan, Reng-Na; Zhu, Hong-Hong; Zhou, Pei-Hua; Li, Hui-Qin; Su, Xiao-Fei; Wu, Jin-Dan; Zhang, Dan-Feng; Ye, Lei; Ma, Jian-Hua

    2017-05-08

    To define the features of glycemic variations in drug naïve type 2 diabetic (T2D) patients with different HbA1c values using continuous glucose monitoring (CGM), a total of 195 drug naïve T2D patients were admitted. The subjects were divided into the following groups: lower HbA1c values (≤8%), moderate HbA1c values (>8% and ≤10%), and higher HbA1c values (>10%). The patients underwent oral glucose tolerance tests and were then subjected to 3-day CGM. The primary endpoint was the differences in the 24-hr mean amplitude of glycemic excursions (MAGE) in patients with different HbA1c values. Patients with higher HbA1c values had larger MAGEs than those in the moderate and lower groups (7.44 ± 3.00 vs. 6.30 ± 2.38, P < 0.05, 7.44 ± 3.00 vs. 5.20 ± 2.35, P < 0.01, respectively). The 24-hr mean glucose concentrations increased incrementally in the patients with lower, moderate and higher HbA1c values. Moreover, the patients with higher HbA1c values exhibited higher peak glucose concentrations and prolongation in the time to peak glucose. Patients with higher HbA1c values had larger MAGE compared with those with lower and moderate HbA1c values. Our data indicated patients with higher HbA1c values should receive special therapy aimed at reducing the larger glycemic variations.

  13. Screening and diagnosis of Hb Quong Sze [HBA2: c.377T > C (or HBA1)] in a prenatal control program for thalassemia.

    PubMed

    Yang, Yu; Lou, Ji-Wu; Liu, Yan-Hui; He, Yi; Li, Dong-Zhi

    2014-01-01

    Hb Quong Sze [Hb QS, HBA2: c.377T > C (or HBA1)] is a common nondeletional thalassemia in southern China. It is one of the major alleles causing nondeletional Hb H (β4) disease in the Chinese population. There is no strategy currently in place that aims to screen using hematological index cutoffs for this variant. This study was carried out to evaluate whether it is effective to use mean corpuscular hemoglobin (MCH) <27.0 pg as a screening test in the first step of screening for Hb QS carriers in southern China. The data of hematological testing in the Hb QS carriers obtained from couples who underwent prenatal thalassemia screening, regardless of the red blood cell (RBC) indices, were retrospectively reviewed. A total of 51 Hb QS carriers were identified, giving a prevalence rate of 0.2%; among these, 45 were Hb QS heterozygotes. The values of hemoglobin (Hb), MCV and mean corpuscular Hb (MCH) in the 45 Hb QS heterozygotes were 13.2 ± 1.8 g/dL, 75.2 ± 3.3 fL and 24.5 ± 0.5 pg, respectively. Eight heterozygotes (17.8%) had an MCV value of >80.0 fL, ranging from 80.9 to 84.1 fL, and would not be detected using the cutoff value of MCV <80.0 fL as a criterion for thalassemia screening. However, if screening had been based on the MCH <27.0 pg value, all 45 Hb QS heterozygotes would have been detected. Using a cutoff value of MCH <27.0 pg in nondeletional thalassemia screening would greatly decrease the DNA diagnosis burden.

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

    PubMed

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

    2013-12-06

    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. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. 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.

  16. Report on HbA1c Proficiency Testing in Asia in 2012

    PubMed Central

    Umemoto, Masao; Hoshino, Tadao; Miyashita, Tetsuo; Tani, Wataru

    2015-01-01

    In 2010, the Japan Diabetes Society decided to introduce the National Glycohemoglobin Standardization Program (NGSP) values into clinical practice. Accordingly, NGSP Certification of Japanese manufacturers of HbA1c-related diagnostic reagents and instruments was initiated in February, 2012, through an NGSP network laboratory, the Asian Secondary Reference Laboratory (ASRL) #1. Traceability to the NGSP reference system can be endorsed by manufacturer certification, as well as by the College of American Pathologists (CAP) survey. Nevertheless, only a few manufacturers participate in the CAP survey in Japan. Thus, proficiency testing (PT) was proposed and executed by ASRL #1. Single-donor whole-blood samples were used for the PT. The participated measurement systems were NGSP certified. Twenty-two laboratories obtained certification through ASRL #1; 2 through the Secondary Reference Laboratory (SRL) #8; and 9 through the SRL #9. The combination plots of the bias data in this PT and in the NGSP certification performed in March and May in 2012 were consistent with each other: mean NGSP values at each level agreed well with the target value. In conclusion, PT using whole blood is useful in endorsing NGSP certification. PMID:25932445

  17. 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.

  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. 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.

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

    PubMed Central

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

    2008-01-01

    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 P21212, 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. PMID:18453702

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

    PubMed

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

    2008-05-01

    The beta-ketoacyl-(acyl carrier protein) synthases (beta-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 A resolution. The crystal is orthorhombic, space group P2(1)2(1)2, with unit-cell parameters a = 72.07, b = 185.57, c = 62.52 A, and contains one homodimer in the asymmetric unit. The subunits adopt the well known alpha-beta-alpha-beta-alpha 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.

  3. Oral health behavior and HbA1c in Indian adults with type 2 diabetes.

    PubMed

    Aggarwal, Ashish; Panat, Sunil R

    2012-01-01

    Prevention and treatment of oral diseases and diabetes require persistent daily self-care, as there is a mutual association between periodontitis severity and level of diabetes control. In this questionnaire study, we investigated oral health behavior, attitudes, and knowledge of diabetes-related factors among 500 Indian adults with type 2 diabetes mellitus. The questionnaire asked about oral self-care, dental visits, self-perceived problems, and knowledge of the relationship between diabetes and oral health. The most recent glycosylated hemoglobin (HbA1c) value was obtained from patient medical records. Overall, 22% of participants reported twice-daily toothbrushing; women were more likely than men to brush twice daily (P< 0.001). With respect to age and diabetes control, participants aged 35-44 years with good diabetes control had the highest rate of twice-daily brushing (P< 0.001). Oral self-care and use of dental services were poor among participants. The present results indicate that Indians with type 2 diabetes need further promotion of oral self-care and regular dental checkups to compensate for their increased risk of oral disease.

  4. Homozygous hemoglobin S (HbSS) presenting with bilateral facial nerve palsy: a case report.

    PubMed

    Ogundunmade, Babatunde Gbolahan; Jasper, Unyime Sunday

    2014-10-16

    Bilateral facial nerve palsy is a relatively rare presentation and often points to a serious underlying medical condition. Several studies have reported presentation of bilateral facial nerve palsy in association with Lyme disease, Guillain-Barre syndrome, systemic lupus erythematosus, human immunodeficiency virus, sarcoidosis, diabetes and Hanson disease. While unilateral facial nerve palsy is sometimes associated with hemiplegia in sickle cell patients, no case of bilateral facial nerve palsy have been reported in the literature. A 29-year-old black African woman who is a known homozygous haemoglobin S (HbSS) presented with bilateral facial nerve palsy. She had the said condition 2 months post delivery of her first child and reported for physiotherapy 3 months post incidence. The pre-treatment House Brackmann Facial Grading Scale (HBFGS) Scores were 3 for right side and 4 for left side. This patient was not on any medication for the facial palsy. After 4 sessions of combination therapy consisting of faradism, facial exercises and massage there was remarkable improvement in the neurological status of the facial muscles. The post treatment House Brackmann Facial Grading Scale score was 2 bilaterally. Bilateral facial nerve palsy may be an initial presentation of sickle cell anemia patients in the absence of other overt clinical presentations. Therefore sickle cell anemia should be considered among others, in the differential diagnosis of bilateral facial nerve palsy. Furthermore, this case report has highlighted the important role of physiotherapy in the management of bilateral facial nerve palsy.

  5. 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.

  6. An international registry of survivors with Hb Bart's hydrops fetalis syndrome

    PubMed Central

    2017-01-01

    Hemoglobin (Hb) Bart's hydrops fetalis syndrome (BHFS) resulting from α0-thalassemia is considered a universally fatal disorder. However, over the last 3 decades, improvements in intrauterine interventions and perinatal intensive care have resulted in increasing numbers of BHFS survivors. We have initiated an international registry containing information on 69 patients, of which 31 are previously unpublished. In this perspective, we analyze the available clinical information to document the natural history of BHFS. In the future, once we have accrued sufficient cases, we aim to build on this study and provide information to allow counseling of at-risk couples. To date, 39 patients have survived beyond the age of 5 years, 18 of whom are now older than 10 years. Based on the available cases, we find evidence to suggest that intrauterine therapy provides benefits during the perinatal and neonatal period; however, it may not provide additional benefits to long-term growth and neurodevelopmental outcomes. Growth retardation is a major adverse long-term outcome among BHFS patients with ∼40% being severely affected in terms of weight and ∼50% in terms of height. There is also an increased risk of neurodevelopmental delay as we find 20% (11/55) of BHFS survivors suffer from a serious delay of ≥6 months. Most patients in the registry require lifelong transfusion and often have associated congenital abnormalities and comorbidities. This perspective is a first step in gathering information to allow provision of informed counseling on the predicted outcomes of affected babies. PMID:28057638

  7. 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.

  8. [Hb Burgos (α1 CD64(E13)(Asp→Asn)): a new hemoglobin variant detected during follow-up of diabetic patients].

    PubMed

    de la Fuente-Gonzalo, Félix; Martínez Nieto, Jorge; Torrejón, María José; Mayor, Luis Antonio; Velasco, Diego; González Fernández, Fernando Ataulfo; Ropero Gradilla, Paloma

    2015-01-06

    The glycated hemoglobin (HbA1c) test by high performance liquid chromatography is a useful tool for the follow-up of diabetes mellitus patients. Some structural hemoglobin (Hb) variants are known to cause interference in the analytical measurement of HbA1c. In this study, it has been characterized a new Hb variant in 4 patients during their regular control of HbA1c. Selective α1 gene sequencing showed a mutation GAC>AAC at codon 64 within exon 2. This produces a change of aspartic acid (Asp) by asparagine (Asn) that does not produce any functional alteration so the resultant molecule behaves as a silent hemoglobinopathy. The structural Hb variants can be detected during the analysis of HbA1c and may alter its values. Though rare, this occurrence signals the need to being aware when measuring HbA1c. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  9. 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…

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

    USDA-ARS?s Scientific Manuscript database

    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 ...

  11. 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.

  12. 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.

  13. 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…

  14. 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.

  15. The first observation of Hb D Punjab beta zero thalassaemia in an English family with 22 cases of unsuspected beta zero thalassaemia minor among its members.

    PubMed Central

    Worthington, S; Lehmann, H

    1985-01-01

    A 36 year old local Englishman from Nuneaton was referred to hospital with suspected glandular fever. Relevant tests were negative and the symptoms subsided in due course. The finding of a hypochromic microcytic blood picture without iron deficiency led to the discovery that he was heterozygous for Hb D and beta thalassaemia. Hb D trait was established in the father of the proband and beta thalassaemia in his mother and a brother. The father's ancestors were miners who came to Nuneaton from Monmouthshire in the 19th century. The mother's ancestors have belonged to the indigenous population of Nuneaton and neighbouring Leicestershire since the 18th century. Twenty local members of her wider family also had thalassaemia. All thalassaemias had a low MCH and raised level of Hb A2. The Hb F level, however, was normal in five, demonstrating the independent segregation of genetic factors influencing the Hb F level in beta thalassaemia trait. PMID:4078867

  16. Genetic origin of Hb D-Los Angeles [beta121(GH4)Glu-->Gln, GAA-->CAA] according to the beta-globin gene cluster haplotypes.

    PubMed

    Atalay, Erol O; Atalay, Ayfer; Ustel, Emre; Yildiz, Sanem; Oztürk, Onur; Köseler, Aylin; Bahadir, Anzel

    2007-01-01

    Hb D-Los Angeles (also known as D-Punjab, D-North Carolina, D-Portugal, D-Chicago and Oak Ridge) is an abnormal hemoglobin (Hb) with an amino acid substitution of glutamine for glutamic acid at codon 121 of the beta-globin gene. The origin and spread of Hb D-Los Angeles is not known. This is due to lack of information and remains to be elucidated. According to published reports, the Hb D-Los Angeles mutation is mostly linked with Mediterranean haplotype I [+ - - - - + +]. Besides the Mediterranean haplotype, a novel haplotype was also reported from Thailand [- - + + - - + + +]. Here we report a new haplotype from Turkey [- + -- + + +] that has not been described before. These results suggest that the Hb D-Los Angeles mutation has at least three different genetic origins.

  17. 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.

  18. VizieR Online Data Catalog: Abundances of 9 HB stars in NGC 6352 (Feltzing+, 2009)

    NASA Astrophysics Data System (ADS)

    Feltzing, S.; Primas, F.; Johnson, R. A.

    2008-10-01

    Metal-rich globular clusters provide important tracers of the formation of our Galaxy. Moreover, and not less important, they are very important calibrators for the derivation of properties of extra-galactic metal-rich stellar populations. Nonetheless, only a few of the metal-rich globular clusters in the Milky Way have been studied using high-resolution stellar spectra to derive elemental abundances. Additionally, Rosenberg et al. identified a small group of metal-rich globular clusters that appeared to be about 2 billion years younger than the bulk of the Milky Way globular clusters. However, it is unclear if like is compared with like in this dataset as we do not know the enhancement of alpha-elements in the clusters and the amount of alpha-elements is well known to influence the derivation of ages for globular clusters. We present a study of elemental abundances for alpha and iron-peak elements for nine HB stars in the metal-rich globular cluster NGC 6352. The elemental abundances are based on high-resolution, high signal-to-noise spectra obtained with the UVES spectrograph on VLT. The elemental abundances have been derived using standard LTE calculations and stellar parameters have been derived from the spectra themselves by requiring ionizational as well as excitational equilibrium. We find that NGC 6352 has [Fe/H]=-0.55, is enhanced in the alpha-elements to about +0.2dex for Ca, Si, and Ti relative to Fe. For the iron-peak elements we find solar values. Based on the spectroscopically derived stellar parameters we find that an E(B-V)=0.24 and (m-M). (3 data files).

  19. Structural Basis of Free Reduced Flavin Generation by Flavin Reductase from Thermus thermophilus HB8*

    PubMed Central

    Imagawa, Takahito; Tsurumura, Toshiharu; Sugimoto, Yasushi; Aki, Kenji; Ishidoh, Kazumi; Kuramitsu, Seiki; Tsuge, Hideaki

    2011-01-01

    Free reduced flavins are involved in a variety of biological functions. They are generated from NAD(P)H by flavin reductase via co-factor flavin bound to the enzyme. Although recent findings on the structure and function of flavin reductase provide new information about co-factor FAD and substrate NAD, there have been no reports on the substrate flavin binding site. Here we report the structure of TTHA0420 from Thermus thermophilus HB8, which belongs to flavin reductase, and describe the dual binding mode of the substrate and co-factor flavins. We also report that TTHA0420 has not only the flavin reductase motif GDH but also a specific motif YGG in C terminus as well as Phe-41 and Arg-11, which are conserved in its subclass. From the structure, these motifs are important for the substrate flavin binding. On the contrary, the C terminus is stacked on the NADH binding site, apparently to block NADH binding to the active site. To identify the function of the C-terminal region, we designed and expressed a mutant TTHA0420 enzyme in which the C-terminal five residues were deleted (TTHA0420-ΔC5). Notably, the activity of TTHA0420-ΔC5 was about 10 times higher than that of the wild-type enzyme at 20–40 °C. Our findings suggest that the C-terminal region of TTHA0420 may regulate the alternative binding of NADH and substrate flavin to the enzyme. PMID:22052907

  20. Structural basis of free reduced flavin generation by flavin reductase from Thermus thermophilus HB8.

    PubMed

    Imagawa, Takahito; Tsurumura, Toshiharu; Sugimoto, Yasushi; Aki, Kenji; Ishidoh, Kazumi; Kuramitsu, Seiki; Tsuge, Hideaki

    2011-12-23

    Free reduced flavins are involved in a variety of biological functions. They are generated from NAD(P)H by flavin reductase via co-factor flavin bound to the enzyme. Although recent findings on the structure and function of flavin reductase provide new information about co-factor FAD and substrate NAD, there have been no reports on the substrate flavin binding site. Here we report the structure of TTHA0420 from Thermus thermophilus HB8, which belongs to flavin reductase, and describe the dual binding mode of the substrate and co-factor flavins. We also report that TTHA0420 has not only the flavin reductase motif GDH but also a specific motif YGG in C terminus as well as Phe-41 and Arg-11, which are conserved in its subclass. From the structure, these motifs are important for the substrate flavin binding. On the contrary, the C terminus is stacked on the NADH binding site, apparently to block NADH binding to the active site. To identify the function of the C-terminal region, we designed and expressed a mutant TTHA0420 enzyme in which the C-terminal five residues were deleted (TTHA0420-ΔC5). Notably, the activity of TTHA0420-ΔC5 was about 10 times higher than that of the wild-type enzyme at 20-40 °C. Our findings suggest that the C-terminal region of TTHA0420 may regulate the alternative binding of NADH and substrate flavin to the enzyme.

  1. A Detailed Study of the Structure of the Nested Planetary Nebula, Hb 12, the Matryoshka Nebula

    NASA Astrophysics Data System (ADS)

    Clark, D. M.; López, J. A.; Edwards, M. L.; Winge, C.

    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), H2 (2.1214 μm), and Brγ (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 H2 emission in the core, whereas the core is prominent in the He I and Brγ recombination lines. The H2 emission is concentrated in equatorial arcs of emission surrounding the core and expanding at ~30 km s-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 Brγ 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-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 Brγ emerging within 0.''1 from the core at ~ ± 40 km s-1.

  2. 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.

  3. Properties and Crystal Structure of Methylenetetrahydrofolate Reductase from Thermus thermophilus HB8

    PubMed Central

    Igari, Sayaka; Ohtaki, Akashi; Yamanaka, Yasuaki; Sato, Yuichi; Yohda, Masafumi; Odaka, Masafumi; Noguchi, Keiichi; Yamada, Kazuhiro

    2011-01-01

    Background Methylenetetrahydrofolate reductase (MTHFR) is one of the enzymes involved in homocysteine metabolism. Despite considerable genetic and clinical attention, the reaction mechanism and regulation of this enzyme are not fully understood because of difficult production and poor stability. While recombinant enzymes from thermophilic organisms are often stable and easy to prepare, properties of thermostable MTHFRs have not yet been reported. Methodology/Principal Findings MTHFR from Thermus thermophilus HB8, a homologue of Escherichia coli MetF, has been expressed in E. coli and purified. The purified MTHFR was chiefly obtained as a heterodimer of apo- and holo-subunits, that is, one flavin adenine dinucleotide (FAD) prosthetic group bound per dimer. The crystal structure of the holo-subunit was quite similar to the β8α8 barrel of E. coli MTHFR, while that of the apo-subunit was a previously unobserved closed form. In addition, the intersubunit interface of the dimer in the crystals was different from any of the subunit interfaces of the tetramer of E. coli MTHFR. Free FAD could be incorporated into the apo-subunit of the purified Thermus enzyme after purification, forming a homodimer of holo-subunits. Comparison of the crystal structures of the heterodimer and the homodimer revealed different intersubunit interfaces, indicating a large conformational change upon FAD binding. Most of the biochemical properties of the heterodimer and the homodimer were the same, except that the homodimer showed ≈50% activity per FAD-bound subunit in folate-dependent reactions. Conclusions/Significance The different intersubunit interfaces and rearrangement of subunits of Thermus MTHFR may be related to human enzyme properties, such as the allosteric regulation by S-adenosylmethionine and the enhanced instability of the Ala222Val mutant upon loss of FAD. Whereas E. coli MTHFR was the only structural model for human MTHFR to date, our findings suggest that Thermus MTHFR will

  4. 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.

  5. Does glucose variability influence the relationship between mean plasma glucose and HbA1c levels in type 1 and type 2 diabetic patients?

    PubMed

    Kuenen, Judith C; Borg, Rikke; Kuik, Dirk J; Zheng, Hui; Schoenfeld, David; Diamant, Michaela; Nathan, David M; Heine, Robert J

    2011-08-01

    The A1C-Derived Average Glucose (ADAG) study demonstrated a linear relationship between HbA(1c) and mean plasma glucose (MPG). As glucose variability (GV) may contribute to glycation, we examined the association of several glucose variability indices and the MPG-HbA(1c) relationship. Analyses included 268 patients with type 1 diabetes and 159 with type 2 diabetes. MPG during 3 months was calculated from 7-point self-monitored plasma glucose and continuous glucose monitoring. We calculated three different measures of GV and used a multiple-step regression model to determine the contribution of the respective GV measures to the MPG-HbA(1c) relationship. GV, as reflected by SD and continuous overlapping net glycemic action, had a significant effect on the MPG-HbA(1c) relationship in type 1 diabetic patients so that high GV led to a higher HbA(1c) level for the same MPG. In type 1 diabetes, the impact of confounding and effect modification of a low versus high SD at an MPG level of 160 mg/dL on the HbA(1c) level is 7.02 vs. 7.43 and 6.96 vs. 7.41. All GV measures showed the same tendency. In only type 1 diabetic patients, GV shows a significant interaction with MPG in the association with HbA(1c). This effect is more pronounced at higher HbA(1c) levels. However, the impact of GV on the HbA(1c) level in type 1 diabetes is modest, particularly when HbA(1c) is close to the treatment target of 7%.

  6. 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.

  7. 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.

  8. Enhanced recovery and purification of P(3HB-co-3HHx) from recombinant Cupriavidus necator using alkaline digestion method.

    PubMed

    Anis, Siti Nor Syairah; Nurhezreen, M I; Sudesh, K; Amirul, A A

    2012-06-01

    A simple, efficient and economical method for the recovery of P(3HB-co-3HHx) was developed using various chemicals and parameters. The initial content of P(3HB-co-3HHx) in bacterial cells was 50-60 wt%, whereas the monomer composition of 3HHx used in this experiments was 3-5 mol%. It was found that sodium hydroxide (NaOH) was the most effective chemical for the recovery of biodegradable polymer. High polyhydroxyalkanoate purity and recovery yield both in the range of 80-90 wt% were obtained when 10-30 mg/ml of cells were incubated in NaOH at the concentration of 0.1 M for 60-180 min at 30 °C and polished using 20 % (v/v) of ethanol.

  9. 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.

  10. FERMI LAT discovery of extended gamma-ray emissions in the vicinity of the HB 3 supernova remnant

    DOE PAGES

    Katagiri, H.; Yoshida, K.; Ballet, J.; ...

    2016-02-11

    We report the discovery of extended gamma-ray emission measured by the Large Area Tele- scope (LAT) onboard the Fermi Gamma-ray Space Telescope in the region of the supernova rem- nant (SNR) HB 3 (G132.7+1.3) and the W3 HII complex adjacent to the southeast of the remnant. W3 is spatially associated with bright 12CO (J=1-0) emission. The gamma-ray emission is spatially correlated with this gas and the SNR. We discuss the possibility that gamma rays originate in inter- actions between particles accelerated in the SNR and interstellar gas or radiation fields. The decay of neutral pions produced in nucleon-nucleon interactions betweenmore » accelerated hadrons and interstellar gas provides a reasonable explanation for the gamma-ray emission. The emission fromW3 is consistent with irradiation of the CO clouds by the cosmic rays accelerated in HB 3.« less

  11. 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

  12. 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.

  13. Oxygen supply (HbO2) in beating hearts of 14 coronary patients obtained by tissue monitoring with optical sensors

    NASA Astrophysics Data System (ADS)

    Frank, Klaus H.; Kloevekorn, P.; Zuendorf, J.; Kessler, Manfred D.

    2002-06-01

    Local intra capillary HbO2 was monitored in beating hearts of 14 patients undergoing coronary bypass surgery. The spectra were measured in the epicardium of the left ventricle, supplied by the left coronary artery (LAD). All selected patients suffered form stenosis or occlusion of two to three vessels. The patients suffered from severe angina and showed hypokinesia in the angiography. Micro-light guide fibers with a diameter of 75micrometers were used for monitoring before and after bypass surgery. These light guides were connected to the Erlanger Micro Light guide Spectro Photometer EMPHO for registration. Local measurements were performed in the epicardium of the left ventricle in 25 areas 2.25cm2 each. Integrated gradient fields were plotted for each of the 14 patients before and after bypass surgery. The mean values of HbO2 in the respective areas were calculated and evaluated against the local value distribution.

  14. Purification, crystallization and preliminary X-ray diffraction study on pyrimidine nucleoside phosphorylase TTHA1771 from Thermus thermophilus HB8

    SciTech Connect

    Shimizu, Katsumi; Kunishima, Naoki

    2007-04-01

    The pyrimidine nucleoside phosphorylase TTHA1771 from T. thermophilus HB8 has been overexpressed, purified and crystallized. The crystals diffract X-rays to 1.8 Å resolution using synchrotron radiation. Pyrimidine nucleoside phosphorylase (PYNP) catalyzes the reversible phosphorolysis of pyrimidines in the nucleotide-synthesis salvage pathway. In order to study the structure–thermostability relationship of this enzyme, PYNP from the extreme thermophile Thermus thermophilus HB8 (TTHA1771) has been cloned, overexpressed and purified. The TTHA1771 protein was crystallized at 291 K using the oil-microbatch method with PEG 4000 as a precipitant. A native data set was collected to 1.8 Å resolution using synchrotron radiation. The crystal belongs to the monoclinic space group P2{sub 1}, with unit-cell parameters a = 58.83, b = 76.23, c = 103.86 Å, β = 91.3°.

  15. 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.

  16. Comparison of the gold standard of hemoglobin measurement with the clinical standard (BGA) and noninvasive hemoglobin measurement (SpHb) in small children: a prospective diagnostic observational study.

    PubMed

    Wittenmeier, Eva; Bellosevich, Sophia; Mauff, Susanne; Schmidtmann, Irene; Eli, Michael; Pestel, Gunther; Noppens, Ruediger R

    2015-10-01

    Collecting a blood sample is usually necessary to measure hemoglobin levels in children. Especially in small children, noninvasively measuring the hemoglobin level could be extraordinarily helpful, but its precision and accuracy in the clinical environment remain unclear. In this study, noninvasive hemoglobin measurement and blood gas analysis were compared to hemoglobin measurement in a clinical laboratory. In 60 healthy preoperative children (0.2-7.6 years old), hemoglobin was measured using a noninvasive method (SpHb; Radical-7 Pulse Co-Oximeter), a blood gas analyzer (clinical standard, BGAHb; ABL 800 Flex), and a laboratory hematology analyzer (reference method, labHb; Siemens Advia). Agreement between the results was assessed by Bland-Altman analysis and by determining the percentage of outliers. Sixty SpHb measurements, 60 labHb measurements, and 59 BGAHb measurements were evaluated. In 38% of the children, the location of the SpHb sensor had to be changed more than twice for the signal quality to be sufficient. The bias/limits of agreement between SpHb and labHb were -0.65/-3.4 to 2.1 g·dl(-1) . Forty-four percent of the SpHb values differed from the reference value by more than 1 g·dl(-1) . Age, difficulty of measurement, and the perfusion index (PI) had no influence on the accuracy of SpHb. The bias/limits of agreement between BGAHb and labHb were 1.14/-1.6 to 3.9 g·dl(-1) . Furthermore, 66% of the BGAHb values differed from the reference values by more than 1 g·dl(-1) . The absolute mean difference between SpHb and labHb (1.1 g·dl(-1) ) was smaller than the absolute mean difference between BGAHb and labHb (1.5 g·dl(-1) /P = 0.024). Noninvasive measurement of hemoglobin agrees more with the reference method than the measurement of hemoglobin using a blood gas analyzer. However, both methods can show clinically relevant differences from the reference method (ClinicalTrials.gov: NCT01693016). © 2015 John Wiley & Sons Ltd.

  17. Telmisartan Inhibits Cell Proliferation by Blocking Nuclear Translocation of ProHB-EGF C-Terminal Fragment in Colon Cancer Cells

    PubMed Central

    Ozeki, Keiji; Tanida, Satoshi; Morimoto, Chie; Inoue, Yoshimasa; Mizoshita, Tsutomu; Tsukamoto, Hironobu; Shimura, Takaya; Kataoka, Hiromi; Kamiya, Takeshi; Nishiwaki, Eiji; Ishiguro, Hiroshi; Higashiyama, Shigeki; Joh, Takashi

    2013-01-01

    Background & Aims Current treatment target toward advanced colorectal cancers is mainly focused on the epidermal growth factor receptor (EGFR) signaling, but its additive effects with chemotherapy are still limited. A disintegrin and metalloproteinase (ADAM) cleaves the proheparin-binding epidermal growth factor like growth factor (proHB-EGF). And soluble HB-EGF activates EGFR. In parallel, the carboxy-terminal fragment of proHB-EGF (HB-EGF-CTF) translocates into the inner nuclear membrane, and subsequently exerts on the regulation of cell proliferation by binding nuclear promyelocytic leukemia zinc finger (PLZF) protein, a transcriptional repressor, thereby causing its nuclear export. We hypothesized that the inhibition of HB-EGF-CTF nuclear translocation may be a new strategy in preventing cell proliferation. Methods 12-O-tetradecanoylphorbor-13-acetate (TPA) was treated to activate ADAM. Nine-thousand chemical compounds were screened for their efficacies in blocking the binding of HB-EGF-CTF to promyelocytic leukemia zinc finger (PLZF) with Alphascreen system. The obtained candidates were then used to block the binding of HB-EGF-CTF to PLZF in colon cancer cells, HT29 and HCT116. Cell proliferation was investigated with a growth curve assay. The intracellular localization, and association between HB-EGF-CTF and PLZF, was assessed with immunofluorescent staining, and immunoprecipitation and Western blotting, respectively. The effects of obtained candidates on EGFR phosphorylation and on nuclear translocation of HB-EGF-CTF and export of PLZF during the angiotensin II type1 receptor (AT1R) knockdown were also investigated. Results Telmisartan and candesartan were found to be potential candidates. Telmisartan inhibited TPA-induced cell proliferation stronger than candesartan. Telmisartan, but not candesartan blocked the nuclear translocation of HB-EGF-CTF, and binding of HB-EGF-CTF to PLZF, during TPA stimulation. Both telmisartan and candesartan did not inhibit TPA

  18. 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.

  19. 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.

  20. Modeling Metabolism and Stage-Specific Growth of Plasmodium falciparum HB3 during the Intraerythrocytic Development Cycle

    DTIC Science & Technology

    2014-01-01

    Wallqvist The human malaria parasite Plasmodium falciparum goes through a complex life cycle, including a roughly 48-hour-long intraerythrocytic...disease warrant basic research into the different mechanisms used by Plasmodium falciparum , the most virulent causative agent of malaria , to survive and...metabolism and stage-specific growth of Plasmodium falciparum HB3 during the intraerythrocytic developmental cycle† Xin Fang, Jaques Reifman* and Anders

  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. 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

  3. 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

  4. FERMI LAT and WMAP observations of the supernova remnant HB 21

    SciTech Connect

    Pivato, Giovanna; Hewitt, John W.; Tibaldo, L.; Acero, F.; Ballet, J.; de Palma, F.; Giordano, F.; Janssen, G. H.; Jóhannesson, G.; Smith, D. A.

    2013-12-04

    Here, 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) × 10–11 erg cm–2 s–1. HB 21 is well modeled by a uniform disk centered at l = 88fdg75 ± 0fdg04, b = +4fdg65 ± 0fdg06 with a radius of 1fdg19 ± 0fdg06. 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 × 1049 erg, while, in a two-zone bremsstrahlung-dominated scenario, the total energy in accelerated particles is ~1 × 1049 erg.

  5. 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.

  6. 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.

  7. HB-EGF Is a Promising Therapeutic Target for Lung Cancer with Secondary Mutation of EGFR(T790M).

    PubMed

    Yotsumoto, Fusanori; Fukagawa, Satoshi; Miyata, Kohei; Nam, Sung Ouk; Katsuda, Takahiro; Miyahara, Daisuke; Odawara, Takashi; Manabe, Sadao; Ishikawa, Toyokazu; Yasunaga, Shin'ichiro; Miyamoto, Shingo

    2017-07-01

    Advanced lung cancer is one of the most lethal malignancies. Many anticancer agents have been developed for lung cancer with epidermal growth factor receptor (EGFR) mutations, but its prognosis remains extremely poor. The development of molecularly-targeted therapies is required for patients with lung cancer with secondary mutation of the EGFR gene. In this study, in order to assess the validity of heparin-binding EGF-like growth factor (HB-EGF) as a therapeutic target for lung cancer with EGFR mutation, we examined the antitumor effects of a specific inhibitor (cross-reacting material 197; CRM197) on lung cancer cells with EGFR mutation. HB-EGF was the most predominantly expressed EGFR ligand in lung cancer cells with EGFR mutation. CRM197 induced significant cell apoptosis and marked suppression of tumorigenicity in lung cancer cells with single or double mutation of EGFR. These results suggest that HB-EGF is a rational target for the treatment of lung cancer with EGFR mutation. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  8. 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.

  9. 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.

  10. NO reactions with sol-gel and solution phase samples of the ferric nitrite derivative of HbA

    PubMed Central

    Roche, Camille J.; Friedman, Joel M.

    2010-01-01

    The reaction of nitric oxide (NO) with the ferric (met) nitrite derivative of human adult hemoglobin Hb is probed for both solution phase and sol-gel encapsulated populations. The evolution of both the Q band absorption spectrum and fitted populations of Hb derivatives are used to show the sequence of events occurring when NO interacts with nitrite bound to a ferric heme in Hb. The sol-gel is used to compare the evolving populations as a function of quaternary state for the starting met nitrite populations. The redox status of intermediates is probed using the CN− anion to trap ferric heme species. The emergent presence of reactive NO species such as N2O3 during the course of the reaction is probed using the fluorescent probe DAF-2 whereas the fluorophore Chemi-fluor is used as an indirect measure of the ability of the reaction to create S-nitrosothiols on glutathione. The results are consistent with the formation of a stable reactive intermediate capable of generating bioactive forms of NO. The patterns observed are consistent with a proposed mechanism whereby NO reacts with the ferric nitrite derivative to generate N2O3. PMID:19919854

  11. 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.

  12. 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).

  13. 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

  14. 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}.

  15. 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

    2017-09-10

    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. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. Modifying effects of maternal Hb concentration on infant birth weight in women receiving prenatal iron-containing supplements: a randomised controlled trial.

    PubMed

    Wang, Linlin; Mei, Zuguo; Li, Hongtian; Zhang, Yali; Liu, Jianmeng; Serdula, Mary K

    2016-02-28

    Concerns have been raised about the benefits of Fe-containing supplements on infant birth weight among women with normal/high Hb levels at baseline. Thus far, no clinical trials have examined whether the effects of prenatal Fe-containing supplements on birth weight vary by maternal Hb levels. We compared the effects of Fe-folic acid (IFA) or multiple micronutrients (MMN) with folic acid (FA) supplements on birth weight among pregnant women with mild/no anaemia or high Hb levels. A double-blind randomised controlled trial was conducted in 2006-2009. In total, 18 775 pregnant women with mild/no anaemia (145 g/l) baseline Hb levels, IFA and MMN supplements increased birth weight by 91·44 (95% CI 3·37, 179·51) g and 107·63 (95% CI 21·98, 193·28) g (P<0·05), respectively, compared with the FA group. No differences were found between the IFA and the MMN group, regardless of maternal Hb concentration. In conclusion, the effects of Fe-containing supplements on birth weight depended on baseline Hb concentrations. The Fe-containing supplements improved birth weight in women with very high Hb levels before 20 weeks of gestation.

  1. Application of Six Sigma Model to Evaluate the Analytical Quality of Four HbA1c Analyzers.

    PubMed

    Maesa, Jos Eacute M; Fern Aacute Ndez-Riejos, Patricia; S Aacute Nchez-Mora, Catalina; Toro-Crespo, Mar Iacute A De; Gonz Aacute Lez-Rodriguez, Concepci Oacute N

    2017-01-01

    The Six Sigma Model is a global quality management system applicable to the determination of glycated hemoglobin (HbA1c). In addition, this model can ensure the three characteristics influencing the patient risk: the correct performance of the analytical method with low inaccuracy and bias, the quality control strategy used by the laboratory, and the necessary quality of the analyte. The aim of this study is to use the Six Sigma Model for evaluating quality criteria in the determination of glycated hemoglobin HbA1c and its application to assess four different HbA1c analyzers. Four HbA1c analyzers were evaluated: HA-8180V®, D-100®, G8®, and Variant II Turbo®. For 20 consecutive days, two levels of quality control (high and low) provided by the manufacturers were measured in each of the instruments. Imprecision (CV), bias, and Sigma values (σ) were calculated with the data obtained and a method decision chart was developed considering a range of quality requirements (allowable total error, TEa). For a TEa = 3%, HA-8180V = 1.54 σ, D-100 = 1.63 σ, G8 = 2.20 σ, and Variant II Turbo = -0.08 σ. For a TEa = 4%, HA-8180V = 2.34 σ, D-100 = 2.32 σ, G8 = 3.74 σ, and Variant II Turbo = 0.16 σ. For a TEa = 10%, HA8180V = 7.12 σ, D-100 = 6.46 σ, G8 = 13.0 σ, and Variant II Turbo = 1.56 σ. Applying the Stockholm consensus and its subsequent Milan review to the results: the maximum level in quality requirements for HbA1c is an allowable total error (TEa) = 3%, G8 is located in region 2 σ (2.20), which is a poor result, and HA-8180V and D-100 are both in region 1 σ (1.54 and 1.63, respectively), which is an unacceptable analytical performance.

  2. NGF and HB-EGF: Potential Biomarkers that Reflect the Effects of Fesoterodine in Patients with Overactive Bladder Syndrome

    PubMed Central

    Kim, Soo Rim; Moon, Yeo Jung; Kim, Sei Kwang

    2015-01-01

    Purpose To determine whether levels of nerve growth factor (NGF) and heparin-binding epidermal growth factor-like growth factor (HB-EGF) can be used to objectively assess overactive bladder syndrome (OAB) treatment outcome and to evaluate the effects of fixed-dose fesoterodine on OAB symptoms. Materials and Methods This study included 124 participants (62 patients with OAB and 62 controls) in Severance Hospital between 2010 and 2012. In patients with OAB, 4 mg fesoterodine was administered once daily. Repeated evaluations of putative biomarker levels, urine creatinine (Cr) levels, and questionnaire responses, including the Overactive Bladder Symptom Score (OABSS) and the Overactive Bladder Questionnaire (OAB q), were performed from baseline to 16 weeks. Results Urinary levels of NGF/Cr (OAB: 1.13±0.9 pg/mg; control: 0.5±0.29 pg/mg) and HB-EGF/Cr (OAB: 8.73±6.55 pg/mg; control: 4.45±2.93 pg/mg) were significantly higher in subjects with OAB than in controls (p<0.001). After 16 weeks of fixed-dose fesoterodine treatment, urinary NGF/Cr levels (baseline: 1.13±0.08 pg/mg; 16 weeks: 0.60±0.4 pg/mg; p=0.02) and HB-EGF/Cr levels significantly decreased (baseline: 8.73±6.55 pg/mg; 16 weeks: 4.72±2.69 pg/mg; p=0.03, respectively). Both the OABSS and OAB q scores improved (p<0.001). However, there were no a statistically significant correlations between these urinary markers and symptomatic scores. Conclusion Urinary levels of NGF and HB-EGF may be potential biomarkers for evaluating outcome of OAB treatment. Fixed-dose fesoterodine improved OAB symptoms. Future studies are needed to further examine the significance of urinary NGF and HB-EGF levels as therapeutic markers for OAB. PMID:25510766

  3. 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

  4. 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.

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

    PubMed

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

    2015-06-01

    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. 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. 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. In patients with type 2 diabetes, canagliflozin provided clinically meaningful body-weight reductions, and the weight loss contributed to reductions in HbA1c and SBP.

  6. Spuriously High Prevalence of Prediabetes Diagnosed by HbA1c in Young Indians Partly Explained by Hematological Factors and Iron Deficiency Anemia

    PubMed Central

    Hardikar, Pallavi S.; Joshi, Suyog M.; Bhat, Dattatray S.; Raut, Deepa A.; Katre, Prachi A.; Lubree, Himangi G.; Jere, Abhay; Pandit, Anand N.; Fall, Caroline H.D.; Yajnik, Chittaranjan S.

    2012-01-01

    OBJECTIVE To examine the influence of glycemic and nonglycemic parameters on HbA1c concentrations in young adults, the majority of whom had normal glucose tolerance. RESEARCH DESIGN AND METHODS We compared the diagnosis of normal glucose tolerance, prediabetes, and diabetes between a standard oral glucose tolerance test (OGTT; World Health Organization 2006 criteria) and HbA1c concentrations (American Diabetes Association [ADA] 2009 criteria) in 116 young adults (average age 21.6 years) from the Pune Children’s Study. We also studied the contribution of glycemic and nonglycemic determinants to HbA1c concentrations. RESULTS The OGTT showed that 7.8% of participants were prediabetic and 2.6% were diabetic. By ADA HbA1c criteria, 23.3% were prediabetic and 2.6% were diabetic. The negative predictive value of HbA1c was 93% and the positive predictive value was 20% (only 20% had prediabetes or diabetes according to the OGTT; this figure was 7% in anemic participants). Of participants, 34% were anemic, 37% were iron deficient (ferritin <15 ng/mL), 40% were vitamin B12 deficient (<150 pmol/L), and 22% were folate deficient (<7 nmol/L). On multiple linear regression analysis, HbA1c was predicted by higher 2-h glucose (R2 = 25.6%) and lower hemoglobin (R2 = 7.7%). When hematological parameters were replaced by ferritin, vitamin B12, and folate, HbA1c was predicted by higher glycemia (R2 = 25.6%) and lower ferritin (R2 = 4.3%). CONCLUSIONS The use of HbA1c to diagnose prediabetes and diabetes in iron-deficient populations may lead to a spuriously exaggerated prevalence. Further investigation is required before using HbA1c as a screening tool in nutritionally compromised populations. PMID:22323413

  7. 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

  8. 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.

  9. HbAHP-25, an In-Silico Designed Peptide, Inhibits HIV-1 Entry by Blocking gp120 Binding to CD4 Receptor

    PubMed Central

    Bashir, Tahir; Patgaonkar, Mandar; Kumar C, Selvaa; Pasi, Achhelal; Reddy, Kudumula Venkata Rami

    2015-01-01

    Human Immunodeficiency Virus (HIV-1) poses a serious threat to the developing world and sexual transmission continues to be the major source of new infections. Therefore, the development of molecules, which prevent new HIV-1 infections, is highly warranted. In the present study, a panel of human hemoglobin (Hb)-α subunit derived peptides and their analogues, with an ability to bind gp120, were designed in-silico and their anti-HIV-1 activity was evaluated. Of these peptides, HbAHP-25, an analogue of Hb-α derived peptide, demonstrated significant anti-HIV-1 activity. HbAHP-25 was found to be active against CCR5-tropic HIV-1 strains (ADA5 and BaL) and CXCR4-tropic HIV-1 strains (IIIB and NL4-3). Surface plasmon resonance (SPR) and ELISA revealed direct interaction between HbAHP-25 and HIV-1 envelope protein, gp120. The peptide prevented binding of CD4 to gp120 and blocked subsequent steps leading to entry and/or fusion or both. Anti-HIV activity of HbAHP-25 appeared to be specific as it failed to inhibit the entry of HIV-1 pseudotyped virus (HIV-1 VSV). Further, HbAHP-25 was found to be non-cytotoxic to TZM-bl cells, VK2/E6E7 cells, CEM-GFP cells and PBMCs, even at higher concentrations. Moreover, HbAHP-25 retained its anti-HIV activity in presence of seminal plasma and vaginal fluid. In brief, the study identified HbAHP-25, a novel anti-HIV peptide, which directly interacts with gp120 and thus has a potential to inhibit early stages of HIV-1 infection. PMID:25915507

  10. Contribution of transcription factor, SP1, to the promotion of HB-EGF expression in defense mechanism against the treatment of irinotecan in ovarian clear cell carcinoma

    PubMed Central

    Miyata, Kohei; Yotsumoto, Fusanori; Nam, Sung Ouk; Odawara, Takashi; Manabe, Sadao; Ishikawa, Toyokazu; Itamochi, Hiroaki; Kigawa, Junzo; Takada, Shuji; Asahara, Hiroshi; Kuroki, Masahide; Miyamoto, Shingo

    2014-01-01

    Ovarian clear cell carcinoma (OCCC) is a worst histological subtype than other ovarian malignant tumor. Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a promising target for ovarian cancer therapy. The aims of this study were to validate the efficacy of HB-EGF–targeted therapy for OCCC and to identify the transcription factor that contributed to the induction of HB-EGF by SN38 treatment in OCCC cells. HB-EGF was highly expressed in OCCC cells, and an increase of HB-EGF was induced by SN38 which had only antitumor effect among conventional anticancer agents on OCCC. A specific inhibitor of HB-EGF, a cross-reacting material 197 (CRM197), led to a synergistic increase in the number of apoptotic OCCC cells with the treatment of SN38. The luciferase assay with 5′-deletion promoter constructs identified a GC-rich element between −125 and −178 (the distal transcription start site was denoted +1) as a cis-regulatory region, and the treatment of SN38 induced luciferase activity in this region. An in silico and chromatin immunoprecipitation analysis estimated that SP1 bound to the cis-regulatory region of HB-EGF in OCCC cells. Real-time PCR and cell viability assays showed that the transfection of a small interfering RNA targeting SP1 suppressed the expression of HB-EGF induced by SN38, resulting in the enhanced sensitivity of SN38. Taken together, these results indicate that induction of HB-EGF expression contributed to defense mechanism against treatment of SN38 through the transcriptional activity of SP1 in OCCC cells. PMID:25060396

  11. 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.

  12. 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

    Giuffrida, Fernando M A; Guedes, Alexis D; Rocco, Eloa R; Mory, Denise B; Dualib, Patricia; Matos, Odelisa S; Chaves-Fonseca, Reine M; Cobas, Roberta A; Negrato, Carlos Antonio; Gomes, Marilia B; Dib, Sergio A

    2012-12-27

    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. 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. 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. 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.

  13. 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

  14. Hb Plasencia [α125(H8)Leu→Arg (α2)] is a frequent cause of α+-thalassemia in the Portuguese population.

    PubMed

    Cunha, Elizabete; Bento, Celeste; Oliveira, Ana; Relvas, Luís; Neves, Joana; Gameiro, Mariline; Barros, Cristina; Araújo, Ana; Macedo, Ana; Rocha, Paula; Costa, Ricardo; Maia, Tabita; Ribeiro, M Letícia

    2013-01-01

    Hb Plasencia is a thalassemic hemoglobin (Hb) mutation caused by a leucine to arginine replacement at residue 125 of the α2-globin chain (HBA2:c.377T>G). This variant was first described in the heterozygous state in association with a very mild α-thalassemic phenotype in three members of a Spanish family from Plasencia, Western Spain. Reviewing the molecular characterization of 308 Portuguese individual suspected of having α-thalassemia (α-thal) we found Hb Plasencia to be the second most frequent mutation after the -α(3.7) deletion.

  15. Impact of HbA1c criterion on the definition of glycemic component of the metabolic syndrome: the China health and nutrition survey 2009.

    PubMed

    Sun, Xingxing; Du, Tingting; Huo, Rui; Yu, Xuefeng; Xu, Lixian

    2013-11-05

    In 2009, a unified definition of metabolic syndrome (MetS) was proposed, of which, the glycemic component is defined on the basis of fasting plasma glucose (FPG) level. Recently, the American Diabetes Association (ADA) recommended the use of glycated hemoglobin (HbA1c) as an alternative to FPG to define prediabetes. Hence, we aim to compare the performance of HbA1c and FPG in the definition of glycemic component of the MetS among Chinese adults. We conducted a cross-sectional analysis of 7641 Chinese participants aged ≥18 years using data from the China Health and Nutrition Survey 2009. MetS was defined according to the consensus criteria in 2009. We compared the use of HbA1c versus FPG in the definition of the glycemic component of MetS. Increased HbA1c value was defined following the criterion of HbA1c cut-off point of ≥5.7% recommended by the ADA. Overall, 1136 (14.9%) had MetS according to FPG ≥ 5.6 mmol/l, and 1640 (21.5%) had MetS according to HbA1c ≥ 5.7%. Compared with individuals with FPG-based diagnosis of MetS, individuals with HbA1c-based diagnosis of MetS were older, had higher levels of LDL-C, magnesium, and transferrin, and lower levels of uric acid. Of those found to have MetS according to either FPG or HbA1c (n = 2008), overlap between HbA1c- and FPG-based diagnosis of MetS was limited (n = 768, 38.2%). The overlap index regarding MetS diagnosed by FPG or HbA1c persisted low in each evaluated subgroup (≤ 50.0%). We note limited