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Sample records for cap alpha thalassemia

  1. Alpha Thalassemia

    Science.gov (United States)

    Alpha Thalassemia Physicians often mistake alpha thalassemia trait for iron deficiency anemia and incorrectly prescribe iron supplements that have no effect 1 on the anemia. αα αα Normal alpha ...

  2. Genetics Home Reference: alpha thalassemia

    Science.gov (United States)

    ... Understand Genetics Home Health Conditions alpha thalassemia alpha thalassemia Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Alpha thalassemia is a blood disorder that reduces the production ...

  3. About Thalassemia

    Science.gov (United States)

    ... I want more information about the Foundation About Thalassemia A Basic Description | Alpha Thalassemia | Beta Thalassemia | Other ... Thalassemia | Downloadable Brochures on Thalassemia and its complications Thalassemia: A Basic Description Thalassemia is the name of ...

  4. Genetics Home Reference: alpha thalassemia X-linked intellectual disability syndrome

    Science.gov (United States)

    ... alpha thalassemia X-linked intellectual disability syndrome alpha thalassemia X-linked intellectual disability syndrome Enable Javascript to ... Download PDF Open All Close All Description Alpha thalassemia X-linked intellectual disability syndrome is an inherited ...

  5. Thalassemia

    Science.gov (United States)

    ... if their spleen has been removed. Slow growth . Children with anemia may grow slowly and have late puberty. Puberty ... by three missing genes or gene changes. Your child may have anemia or develop more serious complications. Alpha thalassemia major , ...

  6. Alpha-thalassemia in northern Thailand. Frequency of deletional types characterized at the DNA level.

    Science.gov (United States)

    Hundrieser, J; Sanguansermsri, T; Papp, T; Flatz, G

    1988-01-01

    The frequency of alpha-thalassemias in northern Thailand was estimated using DNA techniques. Among 106 healthy adult Thais from the Chiangmai area, 28 were shown to carry alpha-globin gene anomalies. There were 19 heterozygotes and 1 homozygote for alpha-thalassemia-2. One of the alpha-thalassemia-2 deletions was of the -alpha 4.2 type and the remaining 20 of the -alpha 3.7 type (subtype I). Deletions of both alpha-globin genes on one chromosome (alpha-thalassemia-1) of the Southeast Asian type were observed in 5 cases, and 3 alpha-globin gene triplications were identified. Compared with a previous report on alpha-thalassemia in northern Thailand which was based on the determination of hemoglobin Bart's in cord blood, the present DNA study reveals a similar frequency of alpha-thalassemia-2 but a considerably lower frequency of alpha-thalassemia-1.

  7. A new alpha(0)-thalassemia deletion found in a Dutch family (--(AW)).

    NARCIS (Netherlands)

    Phylipsen, M.; Vogelaar, I.P.; Schaap, R.A.; Arkesteijn, S.G.; Boxma, G.L.; Helden, W.C. van; Wildschut, I.C.; Bruin-Roest, A.C. de; Giordano, P.C.; Harteveld, C.L.

    2010-01-01

    Alpha-thalassemia is an inherited hemoglobin disorder characterized by a microcytic hypochromic anemia caused by a quantitative reduction of the alpha-globin chain. The majority of the alpha-thalassemias is caused by deletions in the alpha-globin gene cluster. A deletion in the alpha-globin gene clu

  8. Thalassemias

    Science.gov (United States)

    ... page from the NHLBI on Twitter. What Are Thalassemias? Thalassemias (thal-a-SE-me-ahs) are inherited blood ... is passed from parents to children through genes. Thalassemias cause the body to make fewer healthy red ...

  9. Thalassemia

    Science.gov (United States)

    Thalassemias are inherited blood disorders. If you have one, your body makes fewer healthy red blood cells ... oxygen to the body. That leads to anemia. Thalassemias occur most often among people of Italian, Greek, ...

  10. alpha-thalassemia mutations in Khuzestan Province, Southwest Iran.

    Science.gov (United States)

    Zandian, Khodamorad; Nateghi, Jamal; Keikhaie, Bijan; Pedram, Mohammad; Hafezi-Nejad, Nima; Hadavi, Valeh; Oberkanins, Christian; Azarkeivan, Azita; Law, Hai-Yang; Najmabadi, Hossein

    2008-01-01

    Although alpha-thalassemia (alpha-thal) is the most common hereditary hemoglobin (Hb) disorder in Iran, no comprehensive data are so far available on the prevalence of the disease in the province of Khuzestan in Southwest Iran. This study investigates the spectrum of alpha-thal mutations in this region. One hundred and twenty-one subjects from Khuzestan Province, Iran, were initially tested for the three most common Iranian alpha-thal mutations (- alpha3.7, -alpha4.2, and --MED) by gap-polymerase chain reaction (gap-PCR). Reverse hybridization test strips and DNA sequencing were used to identify additional alpha-globin mutations. A total of 131 mutated alpha-globin alleles were identified in these patients. Of the 13 mutations that were detected in Khuzestan Province, Iran, the - alpha3.7 single gene deletion was the most frequently identified variant, representing 62.6% of the total; we also observed significant numbers of individuals with compound heterozygous mutations. On the basis of our results, we strongly recommend screening for the most common mutations to improve the molecular diagnosis of anemia in this region.

  11. Iron metabolism in heterozygotes for hemoglobin E (HbE), alpha-thalassemia1, or beta-thalassemia and in compound heterozygotes for HbE/ beta-thalassemia

    OpenAIRE

    M.B. Zimmermann; Fucharoen, S; Winichagoon, P.; Sirankapracha, P.; Zeder, C.; Gowachirapant, S.; Judprasong, K.; Tanno, T.; Miller, J. L.; Hurrell, R. F.

    2008-01-01

    BACKGROUND: Despite large populations carrying traits for thalassemia in countries implementing universal iron fortification, there are few data on the absorption and utilization of iron in these persons. OBJECTIVE: We aimed to determine whether iron absorption or utilization (or both) in women heterozygous for beta-thalassemia, alpha-thalassemia 1, or hemoglobin E (HbE) differed from that in control subjects and compound HbE/beta-thalassemia heterozygotes. DESIGN: In Thai women (n = 103), re...

  12. Alpha+ -thalassemia protects against anemia associated with asymptomatic malaria: evidence from community-based surveys in Tanzania and Kenya.

    NARCIS (Netherlands)

    Veenemans, J.; Andang'o, P.E.; Mbugi, E.V.; Kraaijenhagen, R.J.; Mwaniki, D.L.; Mockenhaupt, F.P.; Roewer, S.; Olomi, R.M.; Shao, J.F.; Meer, J.W.M. van der; Savelkoul, H.F.; Verhoef, H.

    2008-01-01

    BACKGROUND: In hospital-based studies, alpha(+)-thalassemia has been found to protect against severe, life-threatening falciparum malaria. alpha(+)-Thalassemia does not seem to prevent infection or high parasite densities but rather limits progression to severe disease--in particular, severe malaria

  13. Analysis of alpha hemoglobin stabilizing protein overexpression in murine β-thalassemia.

    Science.gov (United States)

    Nasimuzzaman, Md; Khandros, Eugene; Wang, Xiaomei; Kong, Yi; Zhao, Huifen; Weiss, David; Rivella, Stefano; Weiss, Mitchell J; Persons, Derek A

    2010-10-01

    Excess free alpha-globin is cytotoxic and contributes to the pathophysiology of b-thalassemia. Alpha hemoglobin stabilizing protein (AHSP) is a molecular chaperone that binds free alpha-globin to promote its folding and inhibit its ability to produce damaging reactive oxygen species. Reduced AHSP levels correlate with increased severity of b-thalassemia in some human cohorts, but causal mechanistic relationships are not established for these associations. We used transgenic and lentiviral gene transfer methods to investigate whether supraphysiologic AHSP levels could mitigate the severity of b-thalassemia intermedia by providing an increased sink for the excess pool of alpha-globin chains. We tested wild-type AHSP and two mutant versions with amino acid substitutions that confer 3- or 13-fold higher affinity for alpha-globin. Erythroid overexpression of these AHSP proteins up to 11-fold beyond endogenous levels had no major effects on hematologic parameters in b-thalassemic animals. Our results demonstrate that endogenous AHSP is not limiting for a-globin detoxification in a murine model of b-thalassemia.

  14. Role of alpha-hemoglobin-stabilizing protein in normal erythropoiesis and beta-thalassemia.

    Science.gov (United States)

    Weiss, Mitchell J; Zhou, Suiping; Feng, Liang; Gell, David A; Mackay, Joel P; Shi, Yigong; Gow, Andrew J

    2005-01-01

    Hemoglobin (Hb) synthesis is coordinated by homeostatic mechanisms to limit the accumulation of free alpha or beta subunits, which are cytotoxic. Alpha hemoglobin-stabilizing protein (AHSP) is an abundant erythroid protein that specifically binds free alphaHb, stabilizes its structure, and limits its ability to participate in chemical reactions that generate reactive oxygen species. Gene ablation studies in mice demonstrate that AHSP is required for normal erythropoiesis. AHSP-null erythrocytes are short-lived, contain Hb precipitates, and exhibit signs of oxidative damage. Loss of AHSP exacerbates beta-thalassemia in mice, indicating that altered AHSP expression or function could modify thalassemia phenotypes in humans, a topic that is beginning to be explored in clinical studies. We used biochemical, spectroscopic, and crystallographic methods to examine how AHSP stabilizes alphaHb. AHSP binds the G and H helices of alphaHb on a surface that largely overlaps with the alpha1-beta1 interface of HbA. This result explains previous findings that betaHb can competitively displace AHSP from alphaHb to form HbA tetramer. Remarkably, binding of AHSP to oxygenated alphaHb induces dramatic conformational changes and converts the heme-bound iron to an oxidized hemichrome state in which all six coordinate positions are occupied. This structure limits the reactivity of heme iron, providing a mechanism by which AHSP stabilizes alphaHb. These findings suggest a biochemical pathway through which AHSP might participate in normal Hb synthesis and modulate the severity of thalassemias. Moreover, understanding how AHSP stabilizes alphaHb provides a theoretical basis for new strategies to inhibit the damaging effects of free alphaHb that accumulates in beta-thalassemia.

  15. Limb defects and congenital anomalies of the genitalia in an infant with homozygous alpha-thalassemia.

    Science.gov (United States)

    Abuelo, D N; Forman, E N; Rubin, L P

    1997-01-20

    We describe an infant with homozygous alpha-thalassemia, genital abnormalities, and terminal transverse limb defects, whose limbs demonstrate evidence of loss of tissue and abnormal morphogenesis. We propose these defects were due to either severe fetal anemia or to vascular occlusion by abnormal erythrocytes, resulting in hypoxia of the developing distal limbs and genitalia.

  16. Self-induced vomiting in X-linked {alpha}-thalassemia/mental retardation syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Kurosawa, Kenji; Akatsuka, Akira; Ochiai, Yukikatsu [Jikei Univ. School of Medicine, Tokyo (Japan)] [and others

    1996-06-14

    This report poses the question of whether the vomiting observed in X-linked {alpha}-thalassemia/mental retardation syndrome could be self-induced. The authors present a case history which seems to support this hypothesis. 5 refs., 1 fig.

  17. MFTF-. cap alpha. + T progress report

    Energy Technology Data Exchange (ETDEWEB)

    Nelson, W.D. (ed.)

    1985-04-01

    Early in FY 1983, several upgrades of the Mirror Fusion Test Facility (MFTF-B) at Lawrence Livermore National Laboratory (LLNL) were proposed to the fusion community. The one most favorably received was designated MFTF-..cap alpha..+T. The engineering design of this device, guided by LLNL, has been a principal activity of the Fusion Engineering Design Center during FY 1983. This interim progress report represents a snapshot of the device design, which was begun in FY 1983 and will continue for several years. The report is organized as a complete design description. Because it is an interim report, some parts are incomplete; they will be supplied as the design study proceeds. As described in this report, MFTF-..cap alpha..+T uses existing facilities, many MFTF-B components, and a number of innovations to improve on the physics parameters of MFTF-B. It burns deuterium-tritium and has a central-cell Q of 2, a wall loading GAMMA/sub n/ of 2 MW/m/sup 2/ (with a central-cell insert module), and an availability of 10%. The machine is fully shielded, allows hands-on maintenance of components outside the vacuum vessel 24 h after shutdown, and has provisions for repair of all operating components.

  18. Increased 5. cap alpha. -reductase activity in idiopathic hirsutism

    Energy Technology Data Exchange (ETDEWEB)

    Serafini, P.; Lobo, R.A.

    1985-01-01

    In vitro, genital skin 5..cap alpha..-reductase activity (5..cap alpha..-RA) was measured in ten hirsute women with normal androgen levels (idiopathic hirsutism (IH)) and in ten hirsute women with elevated androgen levels (polycystic ovary syndrome (PCO)) in order to determine the influence of secreted androgens on 5..cap alpha..-RA. In vitro 5..cap alpha..-RA was assessed by incubations of skin with /sup 14/C-testosterone (T) for 2 hours, after which steroids were separated and the radioactivity of dihydrotestosterone (DHT) and 5..cap alpha..-androstane 3..cap alpha..-17..beta..-estradiol (3..cap alpha..-diol) in specific eluates were determined. All androgens were normal in IH with the exception of higher levels of 3..cap alpha..-diol glucuronide which were similar to the levels of PCO. The conversion ratio (CR) of T to DHT in IH and PCO were similar, yet significantly greater than the CR of control subjects. The CR of T to 3..cap alpha..-diol in IH and PCO were similar, yet higher than in control subjects. Serum androgens showed no correlation with 5..cap alpha..-RA, while the CR of T to DHT showed a significant positive correlation with the Ferriman and Gallwey score. The increased 5..cap alpha..-RA in IH appears to be independent of serum androgen levels and is, therefore, an inherent abnormality. The term idiopathic is a misnomer, because hirsutism in these patients may be explained on the basis of increased skin 5..cap alpha..-RA.

  19. Monoclonal antibody based immunoassays to screen for alpha-thalassemia in adults

    Energy Technology Data Exchange (ETDEWEB)

    Epstein, N.; Than, K.A. Culp, K.M. [Isolab, Inc., Akron, OH (United States)] [and others

    1994-09-01

    Alpha-thalassemia (alpha-thal) is characterized by the absence or reduction in synthesis of the alpha-globin chain due to either deletions or other abnormalities involving the alpha-globin genes located on the short arm of chromosome 16. The diploid cells have four alpha chain genes. The deletion of one, two, three or all four of these genes could result in mild to a complete alpha chain deficiency known as the Hydrops fetalis syndrome or alpha-thal-1, which causes fetal death. It is important to develop a sensitive test to detect carriers of alpha-thal-1 trait for genetic counseling. It has recently been observed that the presence of minute amounts of zeta-globin chains (0.01-1%) could serve as a biological marker of alpha-thal carriers. Because high sensitivity is required, we constructed a monoclonal antibody-based immunoassay which can be analyzed either by colorimetric or fluorimetric methods. By testing blood samples from individuals of Southeast Asian ancestry, we were able to show that various forms and combinations of deletions or inactivations of two or three alpha-globin genes results in alpha-thalassemia conditions that have elevated levels of the zeta-chain. Sensitivity achieved in these tests was < 0.1% zeta chain, or as low as 5 ng zeta-chain. Data correlate with results from reversed phase HPLC.

  20. Trafficking of. cap alpha. -L-fucosidase in lymphoid cells

    Energy Technology Data Exchange (ETDEWEB)

    DiCioccio, R.A.; Brown, K.S.

    1987-05-01

    The quantity of ..cap alpha..-L-fucosidase in human serum is determined by heredity. The mechanism controlling levels of the enzyme in serum is unknown. To investigate this, lymphoid cell lines derived from individuals with either low, intermediate or high ..cap alpha..-L-fucosidase in serum were established. Steady state levels of extracellular ..cap alpha..-L-fucosidase protein and activity overlapped among the cell lines. Thus, in vivo serum phenotypes of ..cap alpha..-L-fucosidase are not adequately expressed in this system. ..cap alpha..-L-Fucosidase was also metabolically labelled with /sup 35/S-methionine, immunoprecipitated, and examined by SDS-PAGE. Cells pulse-labelled from 0.25-2 h had a major intracellular form of enzyme (Mr = 58,000). Cells pulsed for 1.5 h and chased for 21 h with unlabeled methionine had an intracellular form of Mr = 60,000 and an extracellular form of Mr = 62,000. Cells treated with chloroquine had only the 58,000-form both intra- and extra-cellularly. Moreover, chloroquine did not effect the quantitative distribution of ..cap alpha..-L-fucosidase between cells and medium. In fibroblasts, chloroquine enhanced the secretion of newly made lysosomal enzymes and blocked the processing of intercellular enzyme forms from a higher to a lower molecular mass. Thus, there are trafficking differences between ..cap alpha..-L-fucosidase in lymphoid cells and lysosomal enzymes in fibroblasts. This suggests that alternative targeting mechanisms for lysosomal enzymes exist in these cells.

  1. Evaluation of Alpha-Thalassemia Mutations in Cases with Hypochromic Microcytic Anemia: The İstanbul Perspective

    Science.gov (United States)

    Karakaş, Zeynep; Koç, Begüm; Temurhan, Sonay; Elgün, Tuğba; Karaman, Serap; Asker, Gamze; Gençay, Genco; Timur, Çetin; Yıldırmak, Zeynep Yıldız; Celkan, Tiraje; Devecioğlu, Ömer; Aydın, Filiz

    2015-01-01

    Objective: Alpha thalassemia syndromes are caused by mutations on one or more of the four α-globin genes. Mutations could be either more commonly deletional or non-deletional. As some deletions (3.7 and 4.2) cause α+-thalassemia, some cause (-20.5, MED, THAI, FIL) α0 -thalassemia. The aim of this study was to determine alpha thalassemia mutations in patients with unsolved hypochromic microcytic anemia and to evaluate types of mutations. Material and Methods: Two hundred six patients with hypochromic microcytic anemia were evaluated for alpha thalassemia. A venous blood sample of 2 mL was drawn from each patient for DNA isolation. The samples were investigated for α-thalassemia mutations by using the Vienna Lab α-Globlin StripAssay TM commercial kit. Results: Fourteen different mutations were determined in 95 (46.1%) patients. The most common mutation was the 3.7 single gene deletion and was found in 37 patients (n=37/95, 39%). Others common mutations were the 20.5 kb double gene deletion (n=20 patients, 21%), MED double gene deletion (n=17 patients, 17.9%), α2 IVS1 (n=10 patients, 10.5%), α2 cd142 Hb Koya Dora (n=6 patients, 6.3%), α2 polyA1 (Saudi type) (n=6 patients, 6.3%), 4.2 single gene deletion (n=4 patients, 4.2%), α1 cd14 (n=2 patients, 2.1%), and -FIL mutation (n=2 patients 2.1%), respectively. Hb Adana, Hb Icaria, α2 init cd and α2 polyA2 (Turkish type) were found in 1% of the patients (n=1). Seven patients (7.4%) had α-thalassemia triplication. In our study, three mutations (Hb Icaria, α1 cd14, α2 init.cd) were determined firstly in Turkey. Seven mutations (-SEA, -THAI, Hb Constant Spring, α2 cd19, α2 cd59, α2 cd125, Hb Paksé) were not determined in this study. Conclusion: Alpha thalassemia should be considered in the differential diagnosis of hypochromic microcytic anemia especially in cases without iron deficiency and b-thalassemia carrier state. Genetic testing should be performed for the suspicious cases. We also recommend that a

  2. Evaluation of Alpha-Thalassemia Mutations in Cases with Hypochromic Microcytic Anemia: The İstanbul Perspective

    Directory of Open Access Journals (Sweden)

    Zeynep Karakaş

    2015-12-01

    Full Text Available INTRODUCTION: Alpha thalassemia syndromes are caused by mutations on one or more of the four α-globin genes. Mutations could be either more commonly deletional or non-deletional. As some deletions (3.7 and 4.2 cause α+-thalassemia, some cause (-20.5, MED, THAI, FIL α0 -thalassemia. The aim of this study was to determine alpha thalassemia mutations in patients with unsolved hypochromic microcytic anemia and to evaluate types of mutations. METHODS: Two hundred six patients with hypochromic microcytic anemia were evaluated for alpha thalassemia. A venous blood sample of 2 mL was drawn from each patient for DNA isolation. The samples were investigated for α-thalassemia mutations by using the Vienna Lab α-Globlin StripAssay TM commercial kit. RESULTS: Fourteen different mutations were determined in 95 (46.1% patients. The most common mutation was the 3.7 single gene deletion and was found in 37 patients (n=37/95, 39%. Others common mutations were the 20.5 kb double gene deletion (n=20 patients, 21%, MED double gene deletion (n=17 patients, 17.9%, α2 IVS1 (n=10 patients, 10.5%, α2 cd142 Hb Koya Dora (n=6 patients, 6.3%, α2 polyA1 (Saudi type (n=6 patients, 6.3%, 4.2 single gene deletion (n=4 patients, 4.2%, α1 cd14 (n=2 patients, 2.1%, and -FIL mutation (n=2 patients 2.1%, respectively. Hb Adana, Hb Icaria, α2 init cd and α2 polyA2 (Turkish type were found in 1% of the patients (n=1. Seven patients (7.4% had α-thalassemia triplication. In our study, three mutations (Hb Icaria, α1 cd14, α2 init.cd were determined firstly in Turkey. Seven mutations (-SEA, -THAI, Hb Constant Spring, α2 cd19, α2 cd59, α2 cd125, Hb Paksé were not determined in this study. DISCUSSION AND CONCLUSION: Alpha thalassemia should be considered in the differential diagnosis of hypochromic microcytic anemia especially in cases without iron deficiency and β-thalassemia carrier state. Genetic testing should be performed for the suspicious cases. We also recommend

  3. Mechanism of radiation graft of methyl-. cap alpha. -fluoroacrylate and. cap alpha. ,. beta. ,. beta. -trifluorostyrene on perfluorinated copolymer. [Cobalt 60

    Energy Technology Data Exchange (ETDEWEB)

    Ivankin, A.N.; Tevlina, A.S.; Zagorets, P.A. (Moskovskij Khimiko-Tekhnologicheskij Inst. (USSR))

    1983-04-01

    The kinetics of radiation-induced graft copolymerization of methyl-..cap alpha..-fluoroacrylate and ..cap alpha.., ..beta.., ..beta..-trifluorostyrene to perfluorinated copolymer of hexafluoropropylene with tetrafluoroethylene has been studied. The orders of the grafting reaction towards the monomer and dose rate as well as the values of rate constants of radiation-induced grafting at various temperatures were determined, the effective activation energy of grafting (20.6 kJ/mol) was calculated. The kinetic scheme of elementary acts of radiation-induced graft copolymerization is discussed.

  4. HB KURDISTAN [ALPHA-47(CE5)ASP-]TYR], A NEW ALPHA-CHAIN VARIANT IN COMBINATION WITH BETA-THALASSEMIA

    NARCIS (Netherlands)

    GIORDANO, PC; HARTEVELD, CL; STRENG, H; Oosterwijk, Jan; HEISTER, JGAM; AMONS, R; BERNINI, LF

    1994-01-01

    We have characterized the structural abnormality of a new alpha chain mutant found in a Kurdish; family. The clinical and hematological investigation of eight individuals have shown that the a variant is associated with a beta degrees-thalassemia mutation (nonsense codon 39). The tryptic peptide map

  5. Protective effect of. cap alpha. -human atrial natriuretic polypeptide (. cap alpha. -hANP) on chemical-induced pulmonary edema

    Energy Technology Data Exchange (ETDEWEB)

    Imamura, T.; Ohnuma, N.; Iwasa, F.; Furuya, M.; Hayashi, Y.; Inomata, N.; Ishihara, T.; Noguchi, T.

    1988-01-01

    It has been established that ..cap alpha..-hANP, the newly discovered peptide extracted from human cardiac atria, has potent natriuretic and hypotensive actions. The authors present investigation is the first to demonstrate that ..cap alpha..-hANP is capable of protecting against pulmonary edema caused by various chemicals, using isolated perfused guinea pig lung system. Lungs were perfused via pulmonary artery with Krebs-Ringer bicarbonate buffer at 5.0 ml/min, and wet weight of lungs and perfusion pressure of pulmonary artery (Pa) were monitored. Bolus injection of Triton-X or CHAPS into cannulated pulmonary artery produced enema as indicated by a massive increase in wet weight and a slight increase in Pa. Constant infusion of ..cap alpha..-hANP through pulmonary artery at 200 ng/ml was effective in causing decrease in wet weight of lung. Perfusion of lung with paraquat or PGF/sub 2..cap alpha..'/, and repeated bolus injection of arachidonic acid or PGE/sub 2/ caused elevation in both wet weight of lung and Pa.

  6. Limb defects in homozygous {alpha}-thalassemia: Report of three cases

    Energy Technology Data Exchange (ETDEWEB)

    Chitayat, D.; Thomas, M.; Silver, M.M. [Univ. of Toronto, Ontario (Canada)] [and others

    1997-01-20

    Homozygosity for the South-Asian {alpha}-thalassemia (--{sup SEA}/) deletion is a serious hematological condition that results, in most cases, in intrauterine or postnatal death due to anemia and severe hypoxia of prenatal onset. A relationship between congenital abnormalities and intrauterine hypoxia has been postulated. However, since homozygosity for the (--{sup SEA}/) deletion is most common in underdeveloped countries where detailed autopsies are lacking, the incidence of congenital abnormalities among these babies has not been well delineated. We report on three newborn infants, homozygous for the (--{sup SEA}/) deletion, who were born with limb defects. We postulate that this combination is the result of prenatal hypoxia which may affect other fetal body organs. This should be taken into consideration when prenatal treatment of affected fetuses, with intrauterine blood transfusion, is suggested. 47 refs., 3 figs.

  7. Complete O(. cap alpha. ) corrections to polarized Compton scattering

    Energy Technology Data Exchange (ETDEWEB)

    Gongora-T, A.; Stuart, R.G.

    1989-04-01

    General expressions for Compton scattering and its O(..cap alpha..) real and virtual corrections are given for electron and photon beams with arbitrary polarization. The expressions obtained are suitable for use in Monte Carlo simulations of Compton polarimeters planned for polarized e/sup +/e/sup -/ colliders. The basis for the calculation are the spinor techniques recently applied to photon and gluon bremsstrahlung. The practical application of these techniques for massive fermions is discussed.

  8. High maltose-producing. cap alpha. -amylase of Penicillium expansum

    Energy Technology Data Exchange (ETDEWEB)

    Doyle, E.M.; Kelly, C.T.; Fogarty, W.M.

    1989-05-01

    An ..cap alpha..-amylase capable of producing exceptionally high levels of maltose (74%) from starch has been identified from a strain of Penicillium expansum. The enzyme is produced extracellularly and was purified to homogeneity by starch adsorption and Sephadex gel filtration chromatography. P. expansum ..cap alpha..-amylase has a pH optimum of 4.5 and is stable in the pH range of 3.6-6.0. Other properties include a temperature optimum of 60/sup 0/C, a molecular weight of 69 000 and and isoelectrtic point of 3.9. The most outstanding feature of the P. expansum enzyme is its ability to yield 14% more maltose and 17.1% less maltotriose than a currently used commercial enzyme. This may be partly explained by the greater affinity of this new enzyme for maltotriose (K/sub m/=0.76 mM) relative to the commercial enzyme, Fungamyl (K/sub m/=2.9 mM). The enzyme reported here is unique among fungal ..cap alpha..-amylases in being able to produce such high levels of maltose and its physicochemical properties suggest that it has potential for commercial development.

  9. Dificuldades na identificação laboratorial da talassemia alfa Difficulty on laboratory identification of alpha thalassemia

    Directory of Open Access Journals (Sweden)

    Karlla Greick Batista Dias-Penna

    2010-04-01

    Full Text Available Introdução: Talassemia alfa é uma síndrome associada à redução da síntese de cadeias de globina do tipo alfa. A gravidade das manifestações clínicas está relacionada com a quantidade de globinas produzida e a estabilidade das cadeias beta presentes em excesso. A talassemia alfa mínima resulta da deleção de apenas um dos quatro genes a (-α/αα. Clinicamente apresenta anemia leve com microcitose ou ausência de anemia, sendo o diagnóstico realizado por meio de visualização da hemoglobina (Hb H por eletroforese alcalina em acetato de celulose ou por identificação de inclusões celulares de Hb H coradas pelo azul de crezil brilhante. Objetivo: Avaliar portadores de talassemia alfa e seus respectivos progenitores, correlacionando perfil hematológico e presença de Hb H, utilizando procedimentos laboratoriais clássicos em três diferentes amostragens. Discussão e conclusão: Os dados obtidos mostram que a presença de Hb H, indicativo de talassemia alfa, pode não ser confirmada em uma análise posterior. Entre os fatores que podem influenciar no não aparecimento de Hb H em pessoa comprovadamente com talassemia alfa está a deficiência de ferro. A talassemia alfa está associada a defeitos envolvendo os genes codificadores da cadeia alfa, mas também pode estar relacionada com desbalanciamento temporário na expressão dos genes globina, diminuição de alfa ou aumento de beta, o que poderia explicar o aparecimento de tetrâmeros de cadeia beta (Hb H, sugerindo diagnóstico de talassemia alfa mínima.Introduction: Alpha thalassemia is a syndrome with associated with the reduction of alpha globin chain synthesis. The severity of clinical manifestations is related to the amount of globins produced and the stability of beta chains that are present in excess. Alpha thalassemia minor is caused by the deletion of one of the four genes a (-α/αα. Clinically, it presents mild anemia with microcytosis or absence of anemia. The

  10. Affinity chromatography of alpha/sub 2/-adrenergic receptors (. cap alpha. /sub 2/AR) from pig cerebral cortex

    Energy Technology Data Exchange (ETDEWEB)

    Repaske, M.G.; Limbird, L.E.

    1986-03-01

    A high capacity, ..cap alpha../sub 2/AR-selective affinity resin (YOH. ag) has been prepared by coupling yohimbinic acid to diaminodipropylamine agarose with 1,3 dicyclohexylcarbodiimide. Unreacted amino groups on the agarose matrix are blocked subsequently by acetylation. One volume of YOH. ag adsorbs 75% of the ..cap alpha../sub 2/AR from 50 volumes of digitonin-solubilized preparation containing 0.2 pmol ..cap alpha../sub 2/AR/mg protein. Digitonin-solubilized preparations are derived from cholate extracts of porcine cerebral cortex containing approx. 0.075 pmol ..cap alpha../sub 2/AR/mg protein. Adsorption of ..cap alpha../sub 2/AR to YOH. ag is selective and thus is blocked by the ..cap alpha..-adrenergic antagonist phentolamine. Adsorbed ..cap alpha../sub 2/AR are eluted with 10 ..mu..M phentolamine (20% yield) after removal of non-related proteins with NaCl gradients. Following hydroxylapatite chromatography to concentrate ..cap alpha..''AR and to remove phentolamine, the ..cap alpha..AR is present at 200-400 pmol/mg protein, assayed using sub-saturating concentrations of (/sup 3/H)-yohimbine. (It is estimated that the specific activity of a homogeneous ..cap alpha../sub 2/AR preparation would be 12,000-16,000 pmol/mg protein.) The availability of large quantities of cortical ..cap alpha../sub 2/AR and a resin easily prepared from commercially-supplied reagents suggests that purification of quantities of ..cap alpha../sub 2/AR sufficient for subsequent biochemical studies is feasible.

  11. Splicing mutation in the ATR-X gene can lead to a dysmorphic mental retardation phenotype without {alpha}-thalassemia

    Energy Technology Data Exchange (ETDEWEB)

    Villard, L.; Lossi, A.M.; Fontes, M. [and others

    1996-03-01

    We have previously reported the isolation of a gene from Xq13 that codes for a putative regulator of transcription (XNP) and has now been shown to be the gene involved in the X-linked {alpha}-thalassemia with mental retardation (ATR-X) syndrome. The widespread expression and numerous domains present in the putative protein suggest that this gene could be involved in other phenotypes. The predominant expression of the gene in the developing brain, as well as its association with neuron differentiation, indicates that mutations of this gene might result in a mental retardation (MR) phenotype. In this paper we present a family with a splice junction mutation in XNP that results in the skipping of an exon and in the introduction of a stop codon in the middle of the XNP-coding sequence. Only the abnormal transcript is expressed in two first cousins presenting the classic ATR-X phenotype (with {alpha}-thalassemia and HbH inclusions). In a distant cousin presenting a similar dysmorphic MR phenotype but not having thalassemia, {approximately}30% of the XNP transcripts are normal. These data demonstrate that the mode of action of the XNP gene product on globin expression is distinct from its mode of action in brain development and facial morphogenesis and suggest that other dysmorphic mental retardation phenotypes, such as Juberg-Marsidi or some sporadic cases of Coffin-Lowry, could be due to mutations in XNP. 20 refs., 5 figs., 2 tabs.

  12. Hb Bronte or alpha93(FG5)Val-->Gly: a new unstable variant of the alpha2-globin gene, associated with a mild alpha(+)-thalassemia phenotype.

    Science.gov (United States)

    Lacerra, Giuseppina; Testa, Rosario; De Angioletti, Maria; Schilirò, Gino; Carestia, Clementina

    2003-08-01

    We report a new unstable variant identified in three carriers of a family from East Sicily; it was named Hb Bronte after the place from which the family originated. DNA sequencing from nucleotides -181 to +894 (alpha1) and to +884 (alpha2) revealed a GTG-->GGG substitution at codon 93 of the alpha2-globin gene. The MCV and MCH values were at the lower end of the normal range in the carriers. On cation exchange high performance liquid chromatography (HPLC), the Hb A2 level was apparently increased to around 6%, and a small abnormal peak (0.3-0.4%) was detected after Hb A2. Two abnormal bands were detected by cellulose acetate electrophoresis: a major band (about 3-4%) migrated between Hb A and Hb F; a minor band (<1%) migrated between Hb A2 and carbonic anhydrase. Normal values of Hb A2 were detected by DEAE microchromatography. On reversed phase HPLC the variant chain was not detected, and most likely it was eluted with the alpha chain peak. The isopropanol stability test was very slightly positive in the carriers. Hemolytic symptoms were absent with the exception of indirect bilirubin, which was at high borderline in 2/3 carriers. In biosynthesis in vitro, the specific activity of the alpha chains was much higher than that of the beta-globin chains, and the alpha/beta biosynthetic ratio in the mother and proband was of the beta-thalassemia (thal) type (2.24 and 2.54, respectively). Time course experiments showed that the increase of the 3H-specific activity of the peak containing normal and variant alpha chains was not linear and was much higher than that of beta chains; moreover, the alpha/beta biosynthetic ratio varied during the 2 hours incubation.

  13. [Rapid development of anemia in a HIV-positive patient with alpha-thalassemia after zidovudine therapy].

    Science.gov (United States)

    Altinbaş, Akif; Ozkaya, Gülşen; Büyükaşik, Yahya; Unal, Serhat

    2007-07-01

    Anemia, which may develop due to direct effect of the virus or indirect effect of zidovudine a widely used antiviral agent for the treatment, is not an uncommon complication in human immundeficiency virus (HIV) infections. In this report, a 26 years old male HIV positive patient who developed rapid anemia in the HAART (Highly active anti-retroviral therapy) protocol including zidovudine, was presented. The patient has been followed since May 2003 without anti-retroviral therapy. He was diagnosed as alpha-thalassemia trait, because of the low mean red blood cell volume (MCV), high red blood cell count and living in an Mediterranian country. However, no treatment for thalassemia had been given in this period, since the other laboratory findings [hemoglobin, hematocrit, red cell distribution width index (RDWI), iron and iron binding capacity, transferrin saturation and ferritin levels] were normal. During the follow-up of patient, HAART protocol with zidovudine, lamivudine and indinavir, was started depending on the findings of low CD4+ T-cell count (443/mm3) and high HIV serum load (1,330,000 copies/ml). In the second month of the therapy the hemoglobin level decreased to 12.9 gr/dL, and then to 9.9 gr/dL in the fourth month, while it was 14.5 gr/dL before anti-retroviral therapy. Although the patient had no hemolysis findings, and his serum folic acid level was normal, folbiol treatment was initiated with the possibility of the presence of folic acid deficiency at cellular level. Anemia resolved with folic acid replacement without discontinuation of zidovudine or a reduction in dosage. It was thought that the presence of alpha-thalassemia co-morbidity has facilitated the development of anti-retroviral-induced anemia in this patient. As a result, it is concluded that thalassemia should be considered in the differential diagnosis of anemia in HIV positive patients, especially for the ones from Mediterranian countries.

  14. Radioimmunoassay determination of decreased amounts of. cap alpha. -L-fucosidase protein in fucosidosis

    Energy Technology Data Exchange (ETDEWEB)

    Andrews-Smith, G.L.; Alhadeff, J.A. (California Univ., San Diego, La Jolla (USA). Dept. of Neurosciences)

    1982-03-15

    Purified human liver ..cap alpha..-L-fucosidase (EC 3.2.1.51) has been radioiodinated by a chloramine-T procedure to a specific activity of 3.7 x 10/sup 6/ dpm/..mu..g protein without altering its apparent Michaelis constant for the 4-methylumbelliferyl substrate. This /sup 125/I-labeled ..cap alpha..-L-fucosidase has been used in development of a competitive binding radioimmunoassay for ..cap alpha..-L-fucosidase which can detect 1-2 ng of enzyme protein and has been employed to quantify the amount of ..cap alpha..-L-fucosidase protein in the liver and spleen from a patient with fucosidosis. Less than 1% of the normal amount of ..cap alpha..-L-fucosidase protein is present suggesting that normal amounts of catalytically inactive ..cap alpha..-L-fucosidase are not found in this disease.

  15. Concept of a (1-. cap alpha. ) performance confidence interval

    Energy Technology Data Exchange (ETDEWEB)

    Leong, H.H.; Johnson, G.R.; Bechtel, T.N.

    1980-01-01

    A multi-input, single-output system is assumed to be represented by some model. The distribution functions of the input and the output variables are considered to be at least obtainable through experimental data. Associated with the computer response of the model corresponding to given inputs, a conditional pseudoresponse set is generated. This response can be constructed by means of the model by using the simulated pseudorandom input variates from a neighborhood defined by a preassigned probability allowance. A pair of such pseudoresponse values can then be computed by a procedure corresponding to a (1-..cap alpha..) probability for the conditional pseudoresponse set. The range defined by such a pair is called a (1-..cap alpha..) performance confidence interval with respect to the model. The application of this concept can allow comparison of the merit of two models describing the same system, or it can detect a system change when the current response is out of the performance interval with respect to the previously identified model. 6 figures.

  16. Hemoglobin A2 values in sickle cell disease patients quantified by high performance liquid chromatography and the influence of alpha thalassemia

    Science.gov (United States)

    da Fonseca, Silvana Fahel; Amorim, Tatiana; Purificação, Antônio; Gonçalves, Marilda; Boa-Sorte, Ney

    2015-01-01

    Background In sickle cell disease, the quantification of Hb A2 is important for the differential diagnosis between sickle cell anemia (Hb SS) and Hb S/β0-thalassemia. Objective To determine Hb A2 levels as quantified by high performance liquid chromatography in patients with sickle cell anemia (Hb SS) and with the SC hemoglobinopathy, with or without concomitant alpha thalassemia. Methods This is a retrospective study of 242 children aged between two and six years with diagnoses of Hb SS or Hb SC. The hemoglobin was evaluated using high performance liquid chromatography and alpha thalassemia [3.7 kb deletion (−α3.7)] was detected by polymerase chain reaction. Patients were classified as homozygous (−α3.7/−α3.7), heterozygous (−α3.7/α), or homozygous wild-type. Analysis of variance was used to compare the mean Hb A2 values between the alpha thalassemia groups. Results The mean (± standard deviation) Hb A2 concentrations in the Hb SS group (n = 135) was 3.68 ± 0.65%. The mean values for individuals with Hb SS and heterozygous (n = 28) or homozygous for alpha thalassemia (n = 3) were 3.98 ± 0.64% and 4.73 ± 0.25%, respectively. The mean Hb A2 of all the Hb SC patients (n = 107) was 4.01 ± 0.507 with 4.29 ± 0.41% and 4.91 ± 0.22% in individuals heterozygous (n = 23) and homozygous for alpha thalassemia (n = 7), respectively. All patients homozygous for alpha thalassemia had Hb A2 levels above 3.5%. However, Hb A2 values above 5.2% were seen in patients with Hb SS and Hb SC, independently of alpha thalassemia. Conclusion Hb A2 levels are elevated in patients with Hb S or Hb C, and are directly influenced by the alpha thalassemia genotypes. PMID:26408362

  17. Improved radioimmunoassay for thymosin. cap alpha. 1 recognizes the N-14 amino terminus

    Energy Technology Data Exchange (ETDEWEB)

    Naylor, P.H.; Goldstein, A.L.

    1986-03-01

    Thymosin ..cap alpha../sub 1/(T..cap alpha../sub 1/) is a biologically active thymic peptide currently undergoing trials as an immunomodulator in cancer patients and patients with immunodeficiencies. Abnormally elevated levels of T..cap alpha../sub 1/ have been found in the serum of individuals with or at risk for AIDS, with T-cell leukemias, and chronic progressive multiple sclerosis. Absorption of the current antibody with a synthetic C-14 fragment of T..cap alpha../sub 1/ results in an antisera specific for the N-14 amino terminus of T..cap alpha../sub 1/, which measures significantly higher levels of T..cap alpha../sub 1/ in serum from normal individuals and significantly increases the sensitivity of the assay. Ongoing studies indicate that this new RIA for T..cap alpha../sub 1/ will be useful in monitoring changes of immunoreactive T..cap alpha../sub 1/ in serum with age and in patients with known or suspected T-cell abnormalities.

  18. Purification and characterization of the human platelet. cap alpha. /sub 2/-adrenergic receptor

    Energy Technology Data Exchange (ETDEWEB)

    Shreeve, S.M.; Kerlavage, A.R.; Fraser, C.M.; Mariani, A.P.; Venter, J.C.

    1986-05-01

    The ..cap alpha../sub 2/-receptor (..cap alpha../sub 2/-R) from human platelets has been purified to homogeneity using a four step process. An affinity column was prepared by coupling p-aminoclonidine to CH-Sepharose 4B via the p-NH/sub 2/ group. Digitonin solubilized ..cap alpha../sub 2/-R bound to the affinity matrix were eluted with 100 ..mu..M phentolamine and directly applied to a DEAE-Sepharose column. Bound receptors were eluted with a linear gradient of 0-500 mM NaCl, pooled and chromatographed on HPLC size exclusion columns. Three peaks of ..cap alpha../sub 2/-R binding were eluted from HPLC columns (t = 33, 42, 47 min). Radioiodination of HPLC eluates and analysis by SDS-PAGE indicated that ..cap alpha../sub 2/-R binding was associated with a 75-85 kDa protein. These data suggest that the ..cap alpha../sub 2/-R may exist in monomeric and oligomeric forms in the purified state and support previous target size data which indicate that the ..cap alpha../sub 2/-R exists as a dimer in the native membrane. The pure radioiodinated ..cap alpha../sub 2/-R (77-85 kDa) is a glycoprotein with terminal sialic acid or N-acetylglucosamine residues and has a pI of 4.1 on column isoelectric focusing. These data are consistent with those previously reported on the partially purified ..cap alpha../sub 2/-R. Electron micrographs confirm the oligomeric nature and size of the pure ..cap alpha../sub 2/-R.

  19. Hemoglobinas AS/alfa talassemia: importância diagnóstica Hemoglobins AS/alpha thalassemia: diagnostic importance

    Directory of Open Access Journals (Sweden)

    Renata Tomé-Alves

    2000-12-01

    , the Sickle Cell beta Thalassemia syndromes, and Hemoglobinopathies in which hemoglobin S is in association with another abnormal hemoglobin, such as hemoglobin S/C. The Sickle Cell trait (hemoglobin AS associated with Alpha Thalassemia presents alterations in the red blood cells morphology, usually absent in the heterozygous for this hemoglobin variant. The interaction between hemoglobin S and alpha Thalassemia has been described as one of the factors responsible for the improvement in the clinical picture of homozygous of hemoglobin S (Sickle Cell Anemia, decreasing the number of episodes of pain. The genetic mechanisms of this influence are evaluated using molecular analyses of the human globin genes. With the objective of verifying the presence of alpha Thalassemia in heterozygous of hemoglobin S, with anemia, sent to the Laboratory of Hemoglobins, Department of Biology, UNESP, São José do Rio Preto, SP, we analyzed 1002 blood samples with Sickle Cell trait, in the period from 1990 to 1998. The samples were picked with EDTA 5% as anticoagulant, after previous authorization of the carriers. Appropriated counseling and management requires definitive diagnosis. For the laboratorial diagnosis the blood samples were submitted to electrophoretic procedures in alkaline and acid pH and cytological evaluation of hemoglobin H. The electrophoretic procedures confirmed the presence of hemoglobin AS. The cytological evaluation evidenced the presence of alpha Thalassemia. Of this total analyzed, 16(1,59% blood samples presented the association between hemoglobin AS and alpha Thalassemia and two individuals belonged of the same family. Our results addressed us to suggest to the routine laboratories, that is important to accomplish the research of alpha Thalassemia among the Sickle Cell trait, with anemia, to verify the interaction with alpha Thalassemia, supplying to the carriers a important information on its hematological profile, genetic pattern of hemoglobinopathies and the

  20. Influence of alpha-thalassemia trait on the prevalence and severity of anemia in pregnancy among women in Kuwait.

    Science.gov (United States)

    Diejomaoh, F M; Haider, M Z; Dalal, H; Abdulaziz, A; D'Souza, T M; Adekile, A D

    2000-01-01

    Alpha-thalassemia is very common in the Kuwaiti population, but its influence on anemia of pregnancy has not been previously investigated. We have screened a group of 59 anemic (Hb or = 11 g/dl) pregnant women was studied for comparison. All the women were in the second or third trimester of pregnancy. Among the 94 women in both groups, 69 (73.4%) had a normal complement of alpha-globin genes (alphaalpha/alphaalpha), 18 (19.1%) were heterozygotes (-alpha/alphaalpha) and 7 (7.4%) were homozygotes (-alpha/-alpha) giving an allele frequency of 17.0%. Among the anemic group, there were 44 (74.6%) individuals with a normal genotype, 9 (15.3%) heterozygotes and 6 (10.2%) homozygotes. In the nonanemic group, the corresponding prevalence figures were 25 (71.4%), 9 (25.7%) and 1 (2.9%), respectively. The difference between these distributions was statistically significant (chi2 = 37.5, p < 0.0001). However, the mean Hb values were similar in heterozygotes, homozygotes and normal individuals. We, therefore, conclude that while the alpha-thal trait affects the prevalence of anemia among pregnant Kuwaiti women, it does not affect its severity.

  1. Subtypes of Alpha Thalassemia Diagnosed at a Medical Center in Jordan

    Directory of Open Access Journals (Sweden)

    Mohammed wael Abu-Ghoush

    2008-10-01

    Full Text Available BACKGROUND: This retrospective analysis study provides the molecular genetics of α-Thalassemia Mutations and identify the genotype of HbH disease in a group of patients at a Medical Center in Jordan. METHODS: A total of 430 subjects were studied. HbH disease was confirmed by Electrophoresis, HPLC and the demonstration of HbH inclusion bodies by supra vital staining. DNA analysis was performed using polymerase chain reaction, restriction enzyme digestion, followed by agarose gel electrophoresis and by reverse- hybridization assay to diagnose and confirm cases suspected α-thalassemia. RESULTS: Four hundred and thirty cases were found to be α-thalassemia trait and this was confirmed by Polymerase Chain Reaction, five different α- thalassemia determinants were observed. Thirty three cases were diagnosed as HbH disease. CONCLUSION: This study helps in the prediction of the phenotype severity by identifying the genotype of HbH patients .The results of the study can be also applied for the genetic counseling to prospective patients with HbH disease, since in severe cases the need may be arise for prenatal diagnosis in population. [TAF Prev Med Bull 2008; 7(5.000: 373-376

  2. Purification and reconstitution of the human platelet. cap alpha. /sub 2/-adrenergic receptor

    Energy Technology Data Exchange (ETDEWEB)

    Regan, J.W.; Cerione, R.A.; Nakata, H.; Benovic, J.L.; DeMarinis, R.M.; Caron, M.G.; Lefkowitz, R.J.

    1986-05-01

    Human platelet ..cap alpha../sub 2/-adrenergic receptors have been purified approx.80,000 fold to apparent homogeneity by a five step chromatographic procedure. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of radioiodinated protein from purified receptor preparations shows a single major band of M/sub r/ 64,000. The competitive binding of ligands to the purified receptor protein shows the proper ..cap alpha../sub 2/-adrenergic specificity. The ..cap alpha../sub 2/-adrenergic receptor contains an essential sulfhydryl residues. Thus, exposure of the purified receptor to the sulfhydryl specific reagent, phenylmercuric chloride (PMC), resulted in a 80% loss of binding activity. This loss of binding activity was prevented when exposure to PMC was done in the presence of ..cap alpha../sub 2/-adrenergic ligands and it was reversed by subsequent exposure to dithiothreitol. Partial proteolysis of purified ..cap alpha../sub 2/-adrenergic receptors was obtained with S. aureus V-8 protease, ..cap alpha..-chymotrypsin and papain. In a comparison with purified ..beta../sub 2/-adrenergic receptors no common partial proteolytic products were found. Partially purified preparations of the ..cap alpha../sub 2/-adrenergic receptor were successfully reconstituted into phospholipid vesicles with the inhibitory guanyl nucleotide-binding regulatory protein, N/sub i/. In these reconstituted preparations, epinephrine could stimulate, and phentolamine could block, the GTPase activity of N/sub i/.

  3. Deletional rearrangement in the human T-cell receptor. cap alpha. -chain locus

    Energy Technology Data Exchange (ETDEWEB)

    de Villartay, J.P.; Lewis, D.; Hockett, R.; Waldmann, T.A.; Korsmeyer, S.J.; Cohen, D.I.

    1987-12-01

    The antigen-specific receptor on the surface of mature T lymphocytes is a heterodimer consisting of polypeptides termed ..cap alpha.. and ..beta... In the course of characterizing human T-cell tumors with an immature (CD4/sup -/, CD8/sup -/) surface phenotype, the authors detected a 2-kilobase ..cap alpha..-related transcript. Analysis of cDNA clones corresponding to this transcript established that a genetic element (which they call TEA, for T early ..cap alpha..) located between the ..cap alpha..-chain variable- and joining-region genes had been spliced to the ..cap alpha.. constant region. The TEA transcript is present early in thymocyte ontogeny, and its expression declines during T-cell maturation. More important, the TEA area functions as an active site for rearrangement within the ..cap alpha.. gene locus. Blot hybridization of restriction enzyme-digested DNA with a TEA probe revealed a narrowly limited pattern of rearrangement in polyclonal thymic DNA, surprisingly different from the pattern expected for the mature ..cap alpha.. gene with its complex diversity. These DNA blots also showed that TEA is generally present in the germ-line configuration in cells expressing the ..gamma..delta heterodimeric receptor and is deleted from mature (..cap alpha beta..-expressing) T-lymphocyte tumors and lines. Moreover, the TEA transcript lacked a long open reading frame for protein but instead possessed multiple copies of a repetitive element resembling those utilized in the heavy-chain class switch of the immunoglobulin genes. The temporal nature of the rearrangements and expression detected by TEA suggests that this recombination could mediate a transition between immature (..gamma..delta-expressing) T cells and mature (..cap alpha beta..-expressing) T cells.

  4. Increased concentration of. cap alpha. - and. gamma. -endorphin in post mortem hypothalamic tissue of schizophrenic patients

    Energy Technology Data Exchange (ETDEWEB)

    Wiegant, V.M.; Verhoef, C.J.; Burbach, J.P.H.; de Wied, D.

    1988-01-01

    The concentrations of ..cap alpha..-, ..beta..- and ..gamma..-endorphin were determined by radioimmunoassay in HPLC fractionated extracts of post mortem hypothalamic tissue obtained from schizophrenic patients and controls. The hypothalamic concentration of ..cap alpha..- and ..gamma..-endorphin was significantly higher in patients than in controls. No difference was found in the concentration of ..beta..-endorphin, the putative precursor of ..cap alpha..- and ..gamma..-endorphins. These results suggest a deviant metabolism of ..beta..-endorphin in the brain of schizophrenic patients. Whether this phenomenon is related to the psychopathology, or is a consequence of ante mortem farmacotherapy, remains to be established.

  5. Crosslinking of. cap alpha. -bungarotoxin to the acetylcholine receptor from Torpedo marmorata by ultraviolet light irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Oswald, R.E. (New York State Veterinary Coll., Ithaca (USA)); Changeux, J.P. (Institut Pasteur, 75 - Paris (France))

    1982-03-22

    The acetylcholine (ACh) receptor purified from the electric organ of Torpedo (sp) is an oligomer composed of 4 different subunits. The ..cap alpha.. subunit is labeled by affinity reagents known to bind to, or in the close vicinity of, the ACh binding site. The ..cap alpha..-toxins from snake venoms behave as competitive antagonists of ACh for its site. The authors have found that ..cap alpha..-/sup 125/I-bungarotoxin (Bgt) can be crosslinked covalently to ACh receptor subunits by simple UV irradiation. This allows the analysis of toxin-receptor crosslinked products without the complication of an intervening 'crosslinking arm'.

  6. Structure of. cap alpha. -phase in two-phase titanium alloys

    Energy Technology Data Exchange (ETDEWEB)

    Gridnev, V.N.; Ivasishin, O.M.; Svechnikov, V.L. (AN Ukrainskoj SSR, Kiev. Inst. Metallofiziki)

    1982-08-01

    The structure of ..cap alpha..-phase in ..beta..-annealed titanium alloys VT 6 and VT 23 and its changes on heating up to ..cap alpha..+..beta.. ..-->.. ..beta.. transformation temperatures with accelerated cooling is studied. An assumption is made that the observed peculiarities of the residual ..cap alpha..-phase structure in alloys after such treatment are the consequence of the relaxation of interphase stresses resulting from a partial polymorphic transformation while the relaxation mechanism is determined by the alloying degree and initial alloy morphology.

  7. Introduction of the human pro. cap alpha. 1(I) collagen gene into pro. cap alpha. 1(I)-deficient Mov-13 mouse cells leads to formation of functional mouse-human hybrid type I collagen

    Energy Technology Data Exchange (ETDEWEB)

    Schnieke, A.; Dziadek, M.; Bateman, J.; Mascara, T.; Harbers, K.; Gelinas, R.; Jaenisch, R.

    1987-02-01

    The Mov-13 mouse strain carries a retroviral insertion in the pro..cap alpha..1(I) collagen gene that prevents transcription of the gene. Cell lines derived from homozygous embryos do not express type I collagen although normal amounts of pro..cap alpha..2 mRNA are synthesized. The authors have introduced genomic clones of either the human or mouse pro..cap alpha..1(I) collagen gene into homozygous cell lines to assess whether the human or mouse pro..cap alpha..1(I) chains can associate with the endogenous mouse pro..cap alpha..2(I) chain to form stable type I collagen. The human gene under control of the simian virus 40 promoter was efficiently transcribed in the transfected cells. Protein analyses revealed that stable heterotrimers consisting of two human ..cap alpha..1 chains and one mouse ..cap alpha..2 chain were formed and that type I collagen was secreted by the transfected cells at normal rates. However, the electrophoretic migration of both ..cap alpha..1(I) and ..cap alpha..2(I) chains in the human-mouse hybrid molecules were retarded, compared to the ..cap alpha..(I) chains in control mouse cells. Inhibition of the posttranslational hydroxylation of lysine and proline resulted in comigration of human and mouse ..cap alpha..1 and ..cap alpha..2 chains, suggesting that increased posttranslational modification caused the altered electrophoretic migration in the human-mouse hybrid molecules. Amino acid sequence differences between the mouse and human ..cap alpha.. chains may interfere with the normal rate of helix formation and increase the degree of posttranslational modifications similar to those observed in patients with lethal perinatal osteogenesis imperfecta. The Mov-13 mouse system should allow the authors to study the effect specific mutations introduced in transfected pro..cap alpha..1(I) genes have on the synthesis, assembly, and function of collagen I.

  8. Synthetic. cap alpha. subunit peptide 125-147 of human nicotinic acetylcholine receptor induces antibodies to native receptor

    Energy Technology Data Exchange (ETDEWEB)

    McCormick, D.J.; Griesmann, G.E.; Huang, Z.; Lennon, V.A.

    1986-03-05

    A synthetic peptide corresponding to residues 125-147 of the Torpedo acetylcholine receptor (AChR) ..cap alpha.. subunit proved to be a major antigenic region of the AChR. Rats inoculated with 50 ..mu..g of peptide (T ..cap alpha.. 125-147) developed T cell immunity and antibodies to native AChR and signs of experimental autoimmune myasthenia gravis. They report the synthesis and preliminary testing of a disulfide-looped peptide comprising residues 125-147 of the human AChR ..cap alpha.. subunit. Peptide H ..cap alpha.. 125-147 differs from T ..cap alpha.. 125-147 at residues 139 (Glu for Gln) and 143 (Ser for Thr). In immunoprecipitation assays, antibodies to Torpedo AChR bound /sup 125/I-labelled H..cap alpha.. 125-147 antibody bound H..cap alpha.. 125-147, but monoclonal antibodies to an immunodominant region of native AChR bound neither H..cap alpha.. 125-147 nor T ..cap alpha.. 125-147. Rats immunized with H ..cap alpha.. 125-147 produced anti-mammalian muscle AChR antibodies that induced modulation of AChRs from cultured human myotubes. Thus, region 125-147 of the human AChR ..cap alpha.. subunit is extracellular in muscle, and is both antigenic and immunogenic. It remains to be determined whether or not autoantibodies to this region may in part cause the weakness or myasthenia gravis in man.

  9. Regulation of the synthesis of barley aleurone. cap alpha. -amylase by gibberellic acid and calcium ions

    Energy Technology Data Exchange (ETDEWEB)

    Jones, R.L.; Carbonell, J.

    1984-09-01

    The effects of gibberellic acid (GA/sub 3/) and calcium ions on the production of ..cap alpha..-amylase and acid phosphatase by isolated aleurone layers of barley (Hordeum vulgare L. cv Himalaya) were studied. Aleurone layers not previously exposed to GA/sub 3/ or CA/sup 2 +/ show qualitative and quantitative changes in hydrolase production following incubation in either GA/sub 3/ or CA/sup 2 +/ or both. In cubation in H/sub 2/O or CA/sup 2 +/ results in the production of low levels of ..cap alpha..-amylase or acid phosphatase. The addition of GA/sub 3/ to the incubation medium causes 10- to 20-fold increase in the amounts of these enzymes released from the tissue, and addition of CA/sup 2 +/ at 10 millimolar causes a further 8- to 9-fold increase in ..cap alpha..-amylase release and a 75% increase in phosphatase release. Production of ..cap alpha..-amylase isoenzymes is also modified by the levels of GA/sub 3/ and CA/sup 2 +/ in the incubation medium. ..cap alpha..-amylase 2 is produced under all conditions of incubation, while ..cap alpha..-amylase 1 appears only when layers are incubated in GA/sub 3/ or GA/sub 3/ plus CA/sup 2 +/. The synthesis of ..cap alpha..-amylases 3 and 4 requires the presence of both GA/sub 3/ and CA/sup 2 +/ in the incubation medium. Laurell rocket immunoelectrophoresis shows that two distinct groups of ..cap alpha..-amylase antigens are present in incubation media of aleurone layers incubated with both GA/sub 3/ and CA/sup 2 +/, while only one group of antigens is found in media of layers incubated in GA/sub 3/ alone. Strontium ions can be substituted for CA/sup 2 +/ in increasing hydrolase production, although higher concentrations of Sr/sup 2 +/ are requried for maximal response. We conclude that GA/sub 3/ is required for the production of ..cap alpha..-amylase 1 and that both GA/sub 3/ and either CA/sup 2 +/ or Sr/sup 2 +/ are required for the production of isoenzymes 3 and 4 of barley aleurone ..cap alpha..-amylase. 22 references, 8

  10. Genetic recombination within the human T-cell receptor. cap alpha. -chain gene complex

    Energy Technology Data Exchange (ETDEWEB)

    Robinson, M.A.; Kindt, T.J.

    1987-12-01

    Genetic analyses of the human T-cell receptor (TCR) ..cap alpha..-chain genes indicate that recombination events may occur frequently within this gene complex. Examination of the inheritance of restriction fragment length polymorphisms (RFLP) detected by using probes for constant or variable region gene segments made it possible to assign TCR..cap alpha.. haplotypes to the 16 parents and 43 offspring of eight families studied. A total of six RFLP, three for the constant region and three for variable region segments, were examined in the present studies. Most enzyme and probe combinations tested revealed no polymorphism and those finally selected for the study showed limited polymorphism in that only two or, in one case, three allelic forms of the gene were seen. In spite of limited variability at this level, extensive heterogeneity was observed for the combinations of markers present in haplotypes, suggesting that frequent recombination events have occurred. Most strikingly, multiple combinations of RFLP occurring in close proximity of the TCR..cap alpha.. constant region gene were observed in this study. A high recombination frequency for the TCR..cap alpha.. gene complex is further supported by the observation that two children, one in each of two families, inherited recombinant TCR..cap alpha.. haplotypes.

  11. Biological activity of 1. cap alpha. -hydroxyvitamin D/sub 2/ in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Reeve, L.E.; Schnoes, H.K.; DeLuca, H.F.

    1978-01-01

    The biological activity of 1..cap alpha..-hydroxyvitamin D/sub 2/ has been determined in vitamin D-deficient rats. In the calcification of the rachitic epiphyseal plate, 1..cap alpha..-hydroxyvitamin D/sub 2/ is more active than 25-hydroxyvitamin D/sub 3/, while it is equally active in stimulating intestinal calcium absorption. On the other hand, it is much less active (one-third to one-fifth) than 25-hydroxyvitamin D/sub 3/ in the mobilization of calcium from bone. In both the intestinal and bone responses, 1..cap alpha..-hydroxyvitamin D/sub 2/ (312 pmol) is active in nephrectomized rats while 15-hydroxyvitamin D/sub 3/ is not.

  12. Beta Thalassemia

    Science.gov (United States)

    Beta thalassemia is found in people of Mediterranean, Middle Eastern, African, South Asian (Indian, Pakistani, etc.), Southeast Asian and Chinese descent. 1 Beta Thalassemia ßß Normal beta globin genes found on chromosomes ...

  13. Transport of. cap alpha. -aminoisobutyric acid into rat parotid after X-irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Bodner, Lipa

    1989-04-01

    Rat parotid gland exposed to 20 Gy X-irradiation exhibits functional alteration 3 days after exposure. The flow rate of saliva and the uptake of ..cap alpha..-aminoisobutyric acid by the gland was reduced to 50% of values for the control non-irradiated glands. When the same gland was studied in an in vitro system it functioned normally. K/sup +/ release and ..cap alpha..-aminoisobutyric acid uptake by the irradiated dispersed acinar cells was comparable to the control. Transport alteration from the circulatory system into the parotid gland may cause the initial radiation-induced damage.

  14. Iron metabolism in heterozygotes for hemoglobin E (HbE), alpha-thalassemia1, or beta-thalassemia and in compound heterozygotes for HbE/ beta-thalassemia

    NARCIS (Netherlands)

    Zimmermann, M.B.; Fucharoen, S.; Winichagoon, P.; Sirankapracha, P.; Zeder, C.; Gowachirapant, S.; Judprasong, K.; Tanno, T.; Miller, J.L.; Hurrell, R.F.

    2008-01-01

    BACKGROUND: Despite large populations carrying traits for thalassemia in countries implementing universal iron fortification, there are few data on the absorption and utilization of iron in these persons. OBJECTIVE: We aimed to determine whether iron absorption or utilization (or both) in women hete

  15. Measurement of the absolute power of subcritical reactors by the Feinman-. cap alpha. method

    Energy Technology Data Exchange (ETDEWEB)

    Sapozhnikov, V.V.; Tyrkich, E.A.; Lukhanin, A.P.; Okhapkin, V.P.

    1974-01-01

    The effect is examined of delay between time intervals on the value of the power measured, using the Feynman-..cap alpha.. method. The absolute power is shown to be practically independent of the delay value at time intervals less than 10/sup -2/ sec.

  16. Effect of heating rate on temperature of titanium alloy (. cap alpha. +. beta. ). -->. beta. transformaton

    Energy Technology Data Exchange (ETDEWEB)

    Gridnev, V.N.; Ivasishin, O.M.; Markovskij, P.E. (AN Ukrainskoj SSR, Kiev. Inst. Metallofiziki)

    1985-01-01

    The effect of doping of two-phase titaniums alloys and morphology of initial structure on the Tsub(t) temperature shift value of (..cap alpha..+..beta..)..--> beta.. transformation depending on heating rate is investigated. It has been found that the Tsub(t) shift occurs in the strictly determined temperature range depending on chemical alloy composition. The Tsub(t) shift is directly proportional to the Ksub(..beta..) coefficient applied as a quantitative alloying characteristic as well as a dimensional factor equal either to the plate thickness or the ..cap alpha..-phase globule diameter depending on the type of initial structure. In the limits of this temperature range the (..cap alpha..+..beta..)..--> beta..-transformation occurs completely according to the diffusion mechanism. The critical heating rate at which maximum permissible Tsub(t) value is attained and above which its stabilization is observed is determined by the same parameters - the alloy doping degree characterized by the Ksub(..beta..) coefficient and the ..cap alpha..-phase crystal dimensions in the initial structure.

  17. Alpha thalassemia/mental retardation syndrome X-linked gene product ATRX is required for proper replication restart and cellular resistance to replication stress.

    Science.gov (United States)

    Leung, Justin Wai-Chung; Ghosal, Gargi; Wang, Wenqi; Shen, Xi; Wang, Jiadong; Li, Lei; Chen, Junjie

    2013-03-01

    Alpha thalassemia/mental retardation syndrome X-linked (ATRX) is a member of the SWI/SNF protein family of DNA-dependent ATPases. It functions as a chromatin remodeler and is classified as an SNF2-like helicase. Here, we showed somatic knock-out of ATRX displayed perturbed S-phase progression as well as hypersensitivity to replication stress. ATRX is recruited to sites of DNA damage, required for efficient checkpoint activation and faithful replication restart. In addition, we identified ATRX as a binding partner of MRE11-RAD50-NBS1 (MRN) complex. Together, these results suggest a non-canonical function of ATRX in guarding genomic stability.

  18. Agonist-promoted desensitization and phosphorylation of. cap alpha. /sub 1/-adrenergic receptors coupled to stimulation of phosphatidylinositol metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Leeb-Lundberg, L.M.F.; Cotecchia, S.; Caron, M.G.; Lefkowitz, R.J.

    1986-03-05

    In the DDT/sub 1/ MF-2 hamster vas deferens smooth muscle cell line the ..cap alpha../sub 1/-adrenergic receptor (..cap alpha../sub 1/-AR) agonist norepinephrine (NE) promotes rapid attenuation of ..cap alpha../sub 1/-AR-mediated phosphatidylinositol (PI) metabolism which is paralleled by rapid phosphorylation of the ..cap alpha../sub 1/-AR. Cells were labeled by incubation with /sup 32/P/sub i/. Coincubation with NE (100 ..mu..M) significantly increases the rate of /sup 32/P-labeling of both PI and phosphatidic acid. Pretreatment of cells with 100 ..mu..M NE (in the presence of 1 ..mu..M propranolol to prevent ..beta..-AR interactions) results in a drastic attenuation of the NE response on PI metabolism. ..cap alpha../sub 1/-AR from labeled cells can be solubilized and purified by affinity chromatography on Affigel-A55414 and wheat germ agglutinin agarose chromatography. SDS-PAGE of purified ..cap alpha../sub 1/-AR shows a NE-promoted increase in phosphorylation of the M/sub r/ 80K ligand binding peptide. Stoichiometry of phosphorylation increases from approx. 1 mol phosphate/mol ..cap alpha../sub 1/-AR in the basal condition to approx. 2.5 after NE treatment. Both desensitization and phosphorylation are rapid being maximal within 10-20 min of agonist exposure. These results together with previous findings that phorbol esters promote rapid ..cap alpha../sub 1/-AR uncoupling and phosphorylation suggest that receptor phosphorylation is an important mechanism of regulation of ..cap alpha../sub 1/-AR receptor responsiveness.

  19. Kinetic model of Bacillus stearothermophilus. cap alpha. -amylase under process conditions

    Energy Technology Data Exchange (ETDEWEB)

    Henderson, W.E.; Teague, W.M.

    1988-11-01

    A model is presented describing starch hydrolysis by Bacillus stearothermophilus ..cap alpha..-amylase at temperatures of 90 to 115/sup 0/C and substrate concentrations of 24 to 36% solids. First order kinetics adequately describe both the enzyme decay and starch hydrolysis reactions. Quantitation of temperature, pH, added calcium and substrate concentration interactive effects on the first order rate constants is aided by applying standard statistical techniques of experimental design and data analysis. A method for determining residual ..cap alpha..-amylase activity in liquefact based on the Phadebas dye release assay, and an osmometry method for determining degree of liquefact hydrolysis are described. Computer implementation of the model allows rapid graphical visualization as well as screening of ideas for improved starch hydrolysis processes.

  20. Radiation electromagnetic effect in germanium crystals under high-energy. cap alpha. -particle irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Kikoin, I.K.; Babichenko, V.S.; Kikoin, L.I.; Lazarev, S.D.; Rzhanov, A.E.; Filippov, V.I.

    1984-05-01

    Results of experimental investigation into radiation electromagnetic effect (REM) in samples of germanium crystals under approximately 40 MeV ..cap alpha..-particle irradiation in a cyclotron are presented. A high level of excitation, volumetric character of generation of non-equilibrium carriers and formation of defects as well as the form of their spatial distribution are shown to result in some peculiarities of the EMF of the REM effect on the particle flux, fluence and sample parameters. Agreement of theoretical calculations, conducted with account of specificity of ..cap alpha..-particle interaction with a crystal, and experimental data is obtained. It is revealed that the REM effect can be applied in obtaining data on spatial distribution of non-equilibrium carrier concentrations along the particle trajectory in the crystal.

  1. Radiation-electromagnetic effect in germanium crystals irradiated with high-energy. cap alpha. particles

    Energy Technology Data Exchange (ETDEWEB)

    Kikoin, I.K.; Babichenko, V.S.; Kikoin, L.I.; Lazarev, S.D.; Rzhanov, A.E.; Filippov, V.I.

    1984-05-01

    An experimental investigation was made of the radiation-electromagnetic effect in germanium crystals irradiated in a cyclotron with ..cap alpha.. particles of energies up to 40 MeV. The high excitation rate, the bulk nature of generation of nonequilibrium carriers and defects, and their spatial distributions gave rise to several special features in the dependence of the emf due to the radiation-electromagnetic effect on the particle flux, fluence, and parameters of samples. Theoretical calculations carried out allowing for the specific nature of the interaction of ..cap alpha.. particles with crystals agreed well with the experimental results. The radiation-electromagnetic effect could be used to obtain information on the nature of the spatial distribution of the density of nonequilibrium carriers along the trajectory of a particle in a crystal.

  2. Factorization of the fragmentation cross sections in relativistic pA and. cap alpha. A interactions

    Energy Technology Data Exchange (ETDEWEB)

    Abashidze, L.I.; Avdeichikov, V.V.; Beznogikh, G.G.; Bogatin, V.I.; Budilov, V.A.; Gorshkov, N.L.; Zlomanchuk, Y.; Zhidkov, N.K.; Lozhkin, O.V.; Mruvchinski, S.

    1985-08-01

    We have experimentally demonstrated the factorization of the cross sections for production of the isotopes /sup 3//sup ,//sup 4/He with kinetic energy T> or approx. =100 MeV emitted at an angle 90/sup 0/ in the lab from the nuclei C, Cu, and Au in bombardment by ..cap alpha.. particles with energy 3.33 GeV/nucleon and by protons with energy 6.6 GeV.

  3. Alpha-thalassemia is associated with a decreased occurrence and a delayed age-at-onset of albuminuria in sickle cell anemia patients.

    Science.gov (United States)

    Nebor, Danitza; Broquere, Cédric; Brudey, Karine; Mougenel, Danielle; Tarer, Vanessa; Connes, Philippe; Elion, Jacques; Romana, Marc

    2010-08-15

    The aim of this study was to identify possible risk factors for albuminuria, an early marker of sickle cell anemia (SCA) glomerulopathy, in a cohort of 189 SCA adult patients followed at the Sickle Cell Center of Guadeloupe, a French Caribbean island. Biological parameters obtained at baseline, alpha-globin gene status, and beta(S) haplotypes were compared in patients stratified accordingly to graded albuminuria. Abnormal albumin excretion rate was detected in half of the studied adult patients and macroalbuminuria occurred in 21.6%. Graded albuminuria was associated with advanced age (p=0.006), systolic blood pressure (p=0.031), and worsened anemia, i.e. low hemoglobin rate (pcell count (phaplotype. Our results strongly suggest a protective effect of alpha-thalassemia against glomerulopathy in SCA adult patients which could be related to a decreased hemolytic rate.

  4. Decreased expression of GRAF1/OPHN-1-L in the X-linked alpha thalassemia mental retardation syndrome

    Directory of Open Access Journals (Sweden)

    Travali Salvatore

    2010-07-01

    Full Text Available Abstract Background ATRX is a severe X-linked disorder characterized by mental retardation, facial dysmorphism, urogenital abnormalities and alpha-thalassemia. The disease is caused by mutations in ATRX gene, which encodes a protein belonging to the SWI/SNF DNA helicase family, a group of proteins involved in the regulation of gene transcription at the chromatin level. In order to identify specific genes involved in the pathogenesis of the disease, we compared, by cDNA microarray, the expression levels of approximately 8500 transcripts between ATRX and normal males of comparable age. Methods cDNA microarray was performed using total RNA from peripheral blood mononuclear cells of ATRX and normal males. Microarray results were validated by quantitative real-time polymerase chain reaction. Results cDNA microarray analysis showed that 35 genes had a lower expression (30-35% of controls while 25 transcripts had a two-fold higher expression in comparison to controls. In the microarray results the probe for oligophrenin-1, a gene known for its involvement in mental retardation, showed a decreased hybridization signal. However, such gene was poorly expressed in blood mononuclear cells and its decrease was not confirmed in the quantitative real-time RT-PCR assay. On the other hand, the expression of an homologous gene, the GTPase regulator associated with the focal adhesion kinase 1/Oligophrenin-1-like (GRAF1/OPHN-1-L, was relatively high in blood mononuclear cells and significantly decreased in ATRX patients. The analysis of the expression pattern of the GRAF1/OPHN-1-L gene in human tissues and organs revealed the predominant brain expression of a novel splicing isoform, called variant-3. Conclusions Our data support the hypothesis of a primary role for altered gene expression in ATRX syndrome and suggest that the GRAF1/OPHN-1-L gene might be involved in the pathogenesis of the mental retardation. Moreover a novel alternative splicing transcript of such

  5. Alpha thalassemia protects sickle cell anemia patients from macro-albuminuria through its effects on red blood cell rheological properties.

    Science.gov (United States)

    Lamarre, Yann; Romana, Marc; Lemonne, Nathalie; Hardy-Dessources, Marie-Dominique; Tarer, Vanessa; Mougenel, Danielle; Waltz, Xavier; Tressières, Benoît; Lalanne-Mistrih, Marie-Laure; Etienne-Julan, Maryse; Connes, Philippe

    2014-01-01

    While chronic hemolysis has been suspected to be involved in the development of glomerulopathy in patients with sickle cell anemia (SCA), no study focused on the implications of blood rheology. Ninety-six adults with SCA at steady state were included in the present cross-sectional study. Three categories were defined: normo-albuminuria (NORMO, n = 41), micro-albuminuria (MICRO, n = 23) and macro-albuminuria (MACRO, n = 32). Blood was sampled to measure hematological and hemorheological parameters, and genomic DNA extraction was performed to detect the presence of α-thalassemia. The prevalence of α-thalassemia was lower in the MACRO group compared with the two other groups. Anemia was more severe in the MACRO compared with the NORMO group leading the former group to exhibit decreased blood viscosity. Red blood cell deformability was lower and red blood cell aggregates strength was greater in the MACRO compared to the two other groups, and this was directly attributed to the lower frequency of α-thalassemia in the former group. Our results show the protective role of α-thalassemia against the development of sickle cell glomerulopathy, and strongly suggest that this protection is mediated through the decrease of anemia, the increase of RBC deformability and the lowering of the RBC aggregates strength.

  6. Accumulation of glycation products in. cap alpha. -H pig lens crystallin and its bearing to diabetic cataract genesis

    Energy Technology Data Exchange (ETDEWEB)

    Vidal, P.; Cabezas-Cerrato, J.

    1988-01-01

    The incorporation of /sup 11/C-glucose in native pig crystalline by in vitro incubation was found, after subsequent dialysis, to affect all 5 classes of crystallin separated by Sepharose CL-6B column chromatography. Though the radioactivity of the ..cap alpha..-H fraction was three times greater than that of any of the others, autoradiographs of SDS-PAGE gels showed /sup 11/C-glucose adducts to be present in all soluble protein subunits, without there being any evidence of preferential glycation of the ..cap alpha..-H subunits. The concentration of stable glycation products in the ..cap alpha..-H chromatographic fraction of soluble crystallins is suggested to be due the addition of glycated material to this fraction as result of glycation-induced hyperaggregation, and not because the ..cap alpha..-H subunits were especially susceptible to glycation.

  7. Estrogen receptor binding radiopharmaceuticals: II. Tissue distribution of 17. cap alpha. -methylestradiol in normal and tumor-bearing rats

    Energy Technology Data Exchange (ETDEWEB)

    Feenstra, A.; Vaalburg, W.; Nolten, G.M.J.; Reiffers, S.; Talma, A.G.; Wiegman, T.; van der Molen, H.D.; Woldring, M.G.

    1983-06-01

    Tritiated 17..cap alpha..-methylestradiol was synthesized to investigate the potential of the carbon-11-labeled analog as an estrogen-receptor-binding radiopharmaceutical. In vitro, 17..cap alpha..-methylestradiol is bound with high affinity to the cytoplasmic estrogen receptor from rabbit uterus (K/sub d/ = 1.96 x 10/sup -10/M), and it sediments as an 8S hormone-receptor complex in sucrose gradients. The compound shows specific uptake in the uterus of the adult rat, within 1 h after injection. In female rats bearing DMBA-induced tumors, specific uterine and tumor uptakes were observed, although at 30 min the tumor uptake was only 23 to 30% of the uptake in the uterus. Tritiated 17..cap alpha..-methylestradiol with a specific activity of 6 Ci/mmole showed a similar tissue distribution. Our results indicate that a 17 ..cap alpha..-methylestradiol is promising as an estrogen-receptor-binding radiopharmaceutical.

  8. Learning about Thalassemia

    Science.gov (United States)

    ... genetic terms used on this page. Learning About Thalassemia What do we know about heredity and thalassemia? ... Information What do we know about heredity and thalassemia? Thalassemia is actually a group of inherited diseases ...

  9. Determination of the M-matrix in d-. cap alpha. elastic scattering from a complete set of experiments

    Energy Technology Data Exchange (ETDEWEB)

    Elsener, K.; Grueebler, W.; Sperisen, F.; Ghazi-Wakili, K.; Koenig, V.; Schmelzbach, P.A.; Vuaridel, B.; Bittcher, M.; Singy, D.; Ulbricht, J.

    1988-05-02

    Six polarization transfer coefficients of the d-..cap alpha.. elastic scattering have been measured at an incident deuteron energy of 11.9 MeV and a scattering angle theta/sub lab/ = 37.3/sup 0/. Together with earlier data on cross section and analyzing powers, a complete set of measurements allows to deduce the d-..cap alpha.. M-matrix directly from experiment.

  10. Control of. cap alpha. -amylase mRNA accumulation by gibberellic acid and calcium in barley aleurone layers

    Energy Technology Data Exchange (ETDEWEB)

    Deikman, J.; Jones, R.L.

    1985-01-01

    Pulse-labeling of barley (Hordeum vulgare L. cv Himalaya) aleurone layers incubated for 13 hours in 2.5 micromolar gibberellic acid (GA/sub 3/) with or without 5 millimolar CaCl/sub 2/ shows that ..cap alpha..-amylase isozymes 3 and 4 are not synthesized in vivo in the absence of Ca/sup 2 +/. No difference was observed in ..cap alpha..-amylase mRNA levels between layers incubated for 12 hours in 2.5 micromolar GA/sub 3/ with 5 millimolar CaCl/sub 2/ and layers incubated in GA/sub 3/ alone. RNA isolated from layers incubated for 12 hours in GA/sub 3/ with and without CA/sup 2 +/. A cDNA clone for ..cap alpha..-amylase was isolated and used to measure ..cap alpha..-amylase mRNA levels in aleurone layers incubated in the presence and absence of Ca/sup 2 +/ was translated in vitro and was found to produce the same complement of translation products regardless of the presence of Ca/sup 2 +/ in the incubation medium. Immunoprecipitation of translation products showed that the RNA for ..cap alpha..-amylase synthesized in Ca/sup 2 +/-deprived aleurone layers was translatable. Ca/sup 2 +/ is required for the synthesis of ..cap alpha..-amylase isozymes 3 and 4 at a step after mRNA accumulation and processing.

  11. Actin capping protein alpha maintains vestigial-expressing cells within the Drosophila wing disc epithelium.

    Science.gov (United States)

    Janody, Florence; Treisman, Jessica E

    2006-09-01

    Tissue patterning must be translated into morphogenesis through cell shape changes mediated by remodeling of the actin cytoskeleton. We have found that Capping protein alpha (Cpa) and Capping protein beta (Cpb), which prevent extension of the barbed ends of actin filaments, are specifically required in the wing blade primordium of the Drosophila wing disc. cpa or cpb mutant cells in this region, but not in the remainder of the wing disc, are extruded from the epithelium and undergo apoptosis. Excessive actin filament polymerization is not sufficient to explain this phenotype, as loss of Cofilin or Cyclase-associated protein does not cause cell extrusion or death. Misexpression of Vestigial, the transcription factor that specifies the wing blade, both increases cpa transcription and makes cells dependent on cpa for their maintenance in the epithelium. Our results suggest that Vestigial specifies the cytoskeletal changes that lead to morphogenesis of the adult wing.

  12. Alpha Thalassemia (For Parents)

    Science.gov (United States)

    ... Development Infections Diseases & Conditions Pregnancy & Baby Nutrition & Fitness Emotions & Behavior School & Family Life First Aid & Safety Doctors & ... molecule that stores the genes that determine hair color, eye color, whether or not a person is ...

  13. Fast diffusion and electrotransport of cobalt, iron and nickel in. cap alpha. -Y

    Energy Technology Data Exchange (ETDEWEB)

    Okafor, I.C.I.; Carlson, O.N. (Ames Lab., IA (USA))

    1982-03-01

    The diffusion and electrotransport properties of cobalt, iron and nickel in ..cap alpha..-Y were determined. Measurements over the temperature range 1290-1600 K showed that all three solutes have high mobilities and that the diffusivities are of the order of 10/sup -5/ - 10/sup -6/ cm/sup 2/ s/sup -1/. Plots of lnD versus 1/T for each solute at several different temperatures gave activation energies for diffusion between 80 and 97 kJ mol/sup -1/. Negative values were obtained for the effective valence of each solute.

  14. Gravimetric determination and radiochemical separation of palladium(II) with ethyl-. cap alpha. -isonitrosoacetoacetate

    Energy Technology Data Exchange (ETDEWEB)

    Manwati, S.J.; Sawant, A.D. (Institute of Science, Bombay (India). Inorganic and Nuclear Chemistry Lab.)

    1984-10-01

    The use of ethyl-..cap alpha..-isonitrosoacetoacetate for the determination of palladium is reported. Pd can be estimated quantitatively from 0.5M to 2M HCl solution. Accurate results are obtained in 1M solution with an accuracy better than 1%. Decontamination values against platinum and other metals usually associated with Pd are greater than 10/sup 5/. The time required for gravimetric determination is about an hour, for radiochemical separation about 25 min and the recovery is better than 90%.

  15. Secondary. cap alpha. -deuterium kinetic isotope effects in solvolyses of ferrocenylmethyl acetate and benzoate in ethanol

    Energy Technology Data Exchange (ETDEWEB)

    Sutic, D. (Univ. of Zagreb, Yugoslavia); Asperger, S.; Borcic, S.

    1982-12-17

    Secondary ..cap alpha..-deuterium kinetic isotope effects (KIE) in solvolyses of ferrocenyldideuteriomethyl acetate and benzoate were determined in 96% (v/v) ethanol, at 25/sup 0/C, as k/sub H//k/sub D/ = 1.24 and 1.26, respectively. The KIEs were also determined in the presence of 0.1 mol dm/sup -3/ lithium perchlorate: the k/sub H//k/ sub D/ values were 1.23 and 1.22 for acetate and benzoate complexes, respectively. The maximum KIE for the C-O bond cleavage of a primary substrate is as large as, or larger than, that of secondary derivatives, which is estimated to be 1.23 per deuterium. The measured KIE of about 12% per D therefore represents a strongly reduced effect relative to its maximum. The solvolyses exhibit ''a special salt effect''. This effect indicates the presence of solvent-separated ion pairs and the return to tight pairs. As the maximum KIE is expected in solvolyses involving transformation of one type of ion pair into another, the strongly reduced ..cap alpha..-D KIE supports the structure involving direct participation of electrons that in the ground state are localized at the iron atom. The alkyl-oxygen cleavage is accompanied by 10-15% acyl-oxygen cleavage.

  16. No effect of 5-fluorouracil on the properties of purified. cap alpha. -amylase from barley half-seeds

    Energy Technology Data Exchange (ETDEWEB)

    Rodaway, S.J.; Kende, H.

    1978-01-01

    Amylase has been purified from de-embryonated seeds of barley (Horedeum vulgare L. cv. Betzes) which have been incubated on 10/sup 6/M gibberellic acid (GA/sub 3/) following 3 days of imbibition in buffer. Incubation of the half-seeds in up to 10/sup -2/ M 5-fluorouracil (5-FU) during the entire incubation period, including imbibition, had no effect on any of the following characteristics of purified ..cap alpha..-amylase: thermal stability in the absence of calcium, molecular weight of the enzyme, isozyme composition, specific activity, or the amount of ..cap alpha..-amylase synthesized by the aleurone tissue. The synthesis of rRNA and tRNA was strongly inhibited by 5-FU, indicating that the analog had entered the aleurone cells. These results are not in agreement with those of Carlson (Nature New Biology 237: 39-41 (1972)) who found that treatment of barley aleurone with 10/sup -4/ M 5-FU to the addition of GA/sub 3/ resulted in decreased thermal stability of GA/sub 3/-induced ..cap alpha..-amylase and who interpreted this as evidence that the mRNA for ..cap alpha..-amylase was synthesized during the imbibition of the aleurone tissue and independently of gibberellin action. Results of the present experiments indicate that the thermal stability of highly purified ..cap alpha..-amylase is not altered by treatment of barley half-seeds with 5-FU, and that 5-FU cannot be used as a probe to examine the timing of ..cap alpha..-amylase mRNA synthesis.

  17. (p,. cap alpha. ) reaction on /sup 98/Mo and /sup 100/Mo. [12. 3 and 15 Mev, angular distributions

    Energy Technology Data Exchange (ETDEWEB)

    Avrigeanu, V.; Bucurescu, D.; Constantinescu, G.; Ivascu, M.; Popescu, D.; Teodorescu, R.

    1975-01-01

    Levels of /sup 95/Nb and /sup 97/Nb were studied with the /sup 98/Mo(p, ..cap alpha..) reaction at 12.3 MeV and the /sup 100/Mo(p, ..cap alpha..) reaction at 15 MeV incident energy, respectively. Angular distributions were determined for the most prominent levels below 2 MeV, and compared with DWBA calculations based on a triton-cluster form factor. The results are compared with level schemes provided by other nuclear reactions. (auth)

  18. K. cap alpha. sup(h) hypersatellite spectrum and K shell double photoionization cross-section for Ar

    Energy Technology Data Exchange (ETDEWEB)

    Mikkola, E.; Ahopelto, J. (Helsinki University of Technology, Espoo (Finland). Lab. of Physics)

    1983-04-01

    The K..cap alpha..sup(h) hypersatellite spectrum of gaseous Ar has been measured in photon excitation with a plane crystal Bragg spectrometer. The experimental energy of K..cap alpha../sub 2/sup(h) line is obtained. The result is in good agreement with available theoretical calculations. The K shell double photoionization cross-section is estimated from the measured hypersatellite intensity and it is compared with existing theoretical calculations based on the shake theory and correlated wave functions.

  19. Determination of the density of states of. cap alpha. -Si:H using the field effect

    Energy Technology Data Exchange (ETDEWEB)

    Goodman, N B; Fritzsche, H; Ozaki, H

    1979-01-01

    A new iterative computer method has been devised for obtaining N(E), the density of gap states, from field effect data without using simplifying approximations. Analysis shows that equally good fits to the data can be obtained over a range of values of the ratio of electron and hole contributions to the conductivity in the bulk and of the field voltage needed to obtain flat bands. The present experimental accuracy is not sufficient to discern detailed structure in N(E). The validity of assuming a parallel shift of the mobility edge with the potential near the interface is being questioned. Field effect data on undoped glow-discharge ..cap alpha..-Si:H subjected to the Staebler-Wronski cycle of illumination and heat treatment are presented and analyzed.

  20. Twisted accretion discs: Pt. 4. Alignment in polytropic discs and low. cap alpha. limit

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, S.

    1988-07-01

    Twisted thin accretion discs are of interest in explaining long-term periodicities in X-ray binaries, the eclipse in Epsilon Aurigae, and perhaps precessing radio jets and possible warped molecular outflows in star-forming regions. Earlier results used isothermal discs to determine the alignment radius, Rsub(a). Now we see how polytropic discs effect earlier results for discs around compact objects and around close binaries. We find that Rsub(a) for polytropic discs can be up to an order of magnitude larger, depending on the polytropic index, the viscosity parameter and the precession mechanism. There is little change in the earlier conclusion that the case for alignment in Her X-1 is marginal, while there is substantial alignment in epsilon Aur. A lower limit is put on ..cap alpha.. for isothermal discs, which is expected to hold for polytropic discs as well. A bound is put on the energy of the perturbed flows.

  1. Bronquite plástica em criança com talassemia alfa Plastic bronchitis in a child with thalassemia alpha

    Directory of Open Access Journals (Sweden)

    Tiago N. Veras

    2005-12-01

    casts and mucous plugging of the tracheobronchial tree. Given that this illness is part of the differential diagnosis of acute respiratory failure, early treatment is important for improved prognosis. The aim of this report is to describe a case of plastic bronchitis in a child with alpha-thalassemia that was treated successfully with endoscopy. DESCRIPTION: A three year old, black, male child, previously healthy, presented with acute respiratory failure and a chest x-ray showing pulmonary atelectasis. There was no evidence of respiratory symptoms or previous allergy state. The diagnosis of plastic bronchitis was made using flexible and rigid bronchoscopy, and confirmed by histopathologic findings. The child progressed well, treatment was based on supportive care and antibiotics were not used. Ten days after discharge, radiographic appearance was normal. Alpha thalassemia was diagnosed through hemoglobin electrophoresis. COMMENTS: Plastic bronchitis is clinically important because has similar presentation to other prevalent diseases, such as foreign body aspiration and asthma. When plastic bronchitis is suspected, endoscopy is indicated in order to confirm diagnosis and define treatment. Plastic bronchitis has been previously described in patients with cystic fibrosis, cardiac surgery and sickle cell disease. In this case, an association with alpha-thalassemia was observed.

  2. Studies on the 1. cap alpha. ,25-dihydroxycholecalciferol-like activity in a calcinagenic plant, Cestrum diurnum, in the chick

    Energy Technology Data Exchange (ETDEWEB)

    Wasserman, R.H. (Cornell Univ., Ithaca, NY); Corradino, R.A.; Krook, L.; Hughes, M.R.; Haussler, M.R.

    1976-04-01

    Cestrum diurnum (day-blooming jessamine) has been proposed to cause calcinosis in horses and cattle in Florida. The present studies investigated some physiological properties of the plant, using the chick as the experimental animal. The inclusion of dried leaf powder in a rachitogenic diet restored intestinal calcium-binding protein synthesis (CaBP) and increased calcium absorption in the cholecalciferol-deficient chick. The estimated level of cholecalciferol-equivalents in the dried leaf was about 30,000 to 35,000 IU/kg. Most of the activity was extractable with methanol : chloroform (2:1), indicating that the major cholecalciferol-like component in C. diurnum was different from the water soluble factor(s) in Solanum malacoxylon. The time course of effect of C. diurnum extract in rachitic chicks was similar to that of 1,25-dihydroxycholecalciferol but the former had a longer lag time. The strontium fed chick, in which the kidney 25-hydroxycholecaliciferol-1..cap alpha..-hydroxylase is inhibited, responded to C. diurnum extract, confirming the 1..cap alpha..,25-dihydroxycholecalciferol-like character of the Cestrum factor. The extract also appeared to interact with the intestinal 1..cap alpha..,25-dihydroxycholecalciferol cytosol receptor although this observation is preliminary. These findings indicate that the 1..cap alpha..,25-dihydroxycholecalciferol-like principle in C. diurnum may cause excessive calcium and phosphate absorption leading to calcinosis.

  3. Effects of thyroid status on presynaptic. cap alpha. 2-adrenoceptor and. beta. -adrenoceptor binding in the rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Atterwill, C.K.; Bunn, S.J.; Atkinson, D.J. (Development Neurobiology Unit, London (UK). Inst. of Neurology); Smith, S.L.; Heal, D.J. (Radcliffe Infirmary, Oxford (UK))

    1984-01-01

    The effect of thyroid status on noradrenergic synaptic function in the mature brain was examined by measuring presynaptic ..cap alpha..2- and postsynaptic ..beta..-adrenoceptors. Repeated triiodothyronine (T/sub 3/) administration to rats (100..mu..g/kg x 14 days hyperthyroid) caused an 18% increase in striatal ..beta..-adrenoceptors as shown by (/sup 3/H)-dihydroalprenolol binding with no change in membranes from cerebral cortex or hypothalamus. In contrast, hypothyroidism (propylthiouracil, PTU x 14 days) produced significant 12% and 30% reductions in striatal and hypothalamic ..beta..-adrenoceptors respectively with no change in the cerebral cortex. Presynaptic ..cap alpha..2-adrenoceptor function was measured in the two dysthyroid states using the clonidine-induced hypoactivity model. Experimental hyperthyroidism increased the degree of clonidine-induced hypoactivity, and suggests increased presynaptic ..cap alpha..2-adrenoceptor function compared with control rats, whereas hypothyroidism suppressed presynaptic ..cap alpha..2-adrenoceptor function. These results show firstly that changes of thyroid status in the mature rat may produce homeostatic alterations at central noradrenergic synapses as reflected by changes in pre- and postsynaptic adrenoceptor function. Secondly, there appear to be T/sub 3/-induced changes in ..beta..-adrenoceptors in the striatum where changes in dopaminergic neuronal activity have previously been demonstrated.

  4. High prevalence of alpha- and beta-thalassemia in the Kadazandusuns in East Malaysia: challenges in providing effective health care for an indigenous group.

    Science.gov (United States)

    Tan, Jin-Ai Mary Anne; Lee, Ping-Chin; Wee, Yong-Chui; Tan, Kim-Lian; Mahali, Noor Fadzlin; George, Elizabeth; Chua, Kek-Heng

    2010-01-01

    Thalassemia can lead to severe transfusion-dependent anemia, and it is the most common genetic disorder in Malaysia. This paper aims to determine the prevalence of thalassemia in the Kadazandusuns, the largest indigenous group in Sabah, East Malaysia. α- and β-thalassemia were confirmed in 33.6% and 12.8%, of the individuals studied respectively. The high prevalence of α- and β-thalassemia in the Kadazandusuns indicates that thalassemia screening, genetic counseling, and prenatal diagnosis should be included as part of their healthcare system. This preliminary paper serves as a baseline for further investigations into the health and genetic defects of the major indigenous population in Sabah, East Malaysia.

  5. High Prevalence of Alpha- and Beta-Thalassemia in the Kadazandusuns in East Malaysia: Challenges in Providing Effective Health Care for an Indigenous Group

    Directory of Open Access Journals (Sweden)

    Jin-Ai Mary Anne Tan

    2010-01-01

    Full Text Available Thalassemia can lead to severe transfusion-dependent anemia, and it is the most common genetic disorder in Malaysia. This paper aims to determine the prevalence of thalassemia in the Kadazandusuns, the largest indigenous group in Sabah, East Malaysia. α- and β-thalassemia were confirmed in 33.6% and 12.8%, of the individuals studied respectively. The high prevalence of α- and β-thalassemia in the Kadazandusuns indicates that thalassemia screening, genetic counseling, and prenatal diagnosis should be included as part of their healthcare system. This preliminary paper serves as a baseline for further investigations into the health and genetic defects of the major indigenous population in Sabah, East Malaysia.

  6. Thalassemia: Healthy Living

    Science.gov (United States)

    ... Thalassemia” More What can a person living with thalassemia do to stay healthy? A healthy lifestyle is ... disorder”, as well as making healthy choices. Managing Thalassemia Thalassemia is a treatable disorder that can be ...

  7. Value of Mentzer index in differentiation between alpha thalassemia carriers and iron deficiency anemia%Mentzer指数在鉴别轻型α地中海贫血与缺铁性贫血中的价值

    Institute of Scientific and Technical Information of China (English)

    梅敏; 帅虎; 朱甫津; 谭尚华

    2011-01-01

    Objective To evaluates the value of Mentzer index ( MI ) in differentiating alpha thalassemia carriers from iron deficiency anemia.Methods The data on alpha thalassemia gene,blood cell count,and serum levels of iron and ferritin were retrospectively analyzed in 151 patients with reduced hemoglobin A2( HbA2 )levels on hemoglobin electrophoresis.Based on α -globin gene analysis and levels of iron and ferritin,the patients were assigned to alpha thalassemia carriers group ( n =90 ),or iron deficiency anemia group ( n =61 ).Results MI differed significantly between iron deficiency anemia group and alpha thalassemia carriers with normal iron group ( P < 0.01 ),iron deficiency anemia group and alpha thalassemia carriers with iron deficiency group ( P< 0.01 ),iron deficiency anemia group and alpha thalassemia carriers group ( P < 0.01 ); but did not differ significantly between alpha thalassemia carriers with normal iron group and alpha thalassemia carriers with iron deficiency group ( P> 0.05 ).The area under the curve ( AUC ) for MI of receiver operating characteristic curve ( ROC ) was 0.849 between iron deficiency anemia group and alpha thalassemia carriers group,and the cut-off point was 13.1.As MI was -- 13.1,the sensitivity for detecting iron deficiency anemia was 96.7%,specificity 61.1%,and Youden index 0.58.If MI combined with RDW,the sensitivity was 100%.Conclusions Mentzer index has certain accuracy in differentiating alpha thalassemia carriers with reduced HbA2 levels from iron deficiency anemia.Both MI and RDW under the cut-off point can exclude the possibility of iron deficiency anemia.%目的 评估Mentzer指数(Mentzer index,MI)在鉴别HbA2减低中轻型α地中海贫血与缺铁性贫血中的价值.方法 回顾本院3年来血红蛋白电泳中HbA2减低的151例人群的α地贫基因、血常规、铁蛋白、血清铁数据,根据地贫基因分析和铁蛋白、血清铁水平将其分成2组:轻型α地中海贫血组(n=90),

  8. Toxin a from Clostridium difficile binds to rabbit erythrocyte glycolipids with therminal Gal. cap alpha. 1-3Gal. beta. 1-4GlcNaC sequences

    Energy Technology Data Exchange (ETDEWEB)

    Clark, G.F.; Krivan, H.; Wilkins, T.; Smith, D.F.

    1987-05-01

    Toxin A is one of two clostridial toxins implicated as the causative agent of pseudomembranous colitis in patients undergoing postoperative antibiotic therapy. Evidence that the carbohydrate binding determinant for this toxin is a glycoconjugate(s) with non-reducing Gal..cap alpha..1-3Gal..beta..1-4GlcNAc has recently been reported. Specific agglutination of rabbit erythrocytes by Toxin A is inhibited by bovine thyroglobulin and prevented by pretreatment of cells with ..cap alpha..-galactosidase. Total lipid extracts from rabbit erythrocytes were subjected to thin layer chromatography and the chromatogram overlaid with purified /sup 125/I-labeled Toxin A. Two major and several minor toxin-binding glycolipids were detected following autoradiography. The major toxin-binding glycolipids were identified as pentasaccharide- and decasaccharide-ceramides expressing terminal Gal..cap alpha..1-3Gal..beta..1-4GlcNAc sequences. Treatment of the toxin-binding glycolipids with ..cap alpha..-galactosidase abolished binding. Forsmann glycolipid, globoside, Gal..cap alpha..1-4 Gal..beta..1-4Glc-cer, and Gal..cap alpha..1-3Gal..beta..1-4Glc-cer did not bind the toxin. These observations are consistent with the proposed carbohydrate specificity of the toxin for the non-reducing terminal sequence, Gal..cap alpha..1-3Gal..beta..1-4GlcNAc.

  9. Sulphidation behaviour of. beta. -NiAl-. cap alpha. -Cr pseudobinary alloys

    Energy Technology Data Exchange (ETDEWEB)

    Godlewska, E.; Godlewski, K.; Mrowec, S.

    1987-03-01

    The sulphidation behaviour of alloys belonging to the ..beta..-NiAl-..cap alpha..-Cr pseudobinary system was studied at S/sub 2/ pressures P/sub S2/ of 5-2 x 10/sup 3/ Pa and temperatures of 1173 and 1273 K. The alloys contained 0, 4, 10 and 20 at.% Cr and the atomic ratio of nickel to aluminium was always 1 to 1. Kinetic measurements were carried out in a thermogravimetric set-up. The sulphidation rate increased with temperature, S/sub 2/ pressure and chromium concentration in the alloy. The scale morphology and composition for each alloy studied were influenced by the sulphidation parameters. The scales were usually of a multiphase and multilayer nature with varying proportions of Al/sub 2/S/sub 3/, Ni/sub 3/S/sub 2/ and Cr/sub x/S. The innermost part of the scale was always rich in aluminium or aluminium and chromium, the amount of nickel being the highest on the surface. At 1273 K and P/sub S2/ = 5 Pa the scales on chromium-rich alloys consisted of Al/sub 2/S/sub 3/ and Cr/sub x/S only.

  10. Comparison of holocellulose,. cap alpha. -cellulose and lignin contents of trunk and branch wood of some conifers of Pakistan

    Energy Technology Data Exchange (ETDEWEB)

    Mahmood, A.; Mahmood, T.

    1985-01-01

    Samples of trunk and branchwood of 7 conifer species growing under forest conditions in Pakistan were analysed to evaluate the suitability of branchwood for the pulp and paper industries. Holocellulose content in the branchwood of Cedrus deodara, Juniperus polycarpos, Pinus halepensis and Pinus roxburghii-amerciana(.) was comparable with values for their truckwood. The branchwood of Abies prindrow, P. rotberghii and P. wallichiana contained less holocellusose than the trunkwood. The branchwood of A. pindrow, C. deodara, and P. roxburghii-americana contained less ..cap alpha..-cellulose than the trunkwood, but ..cap alpha..-cellulose contents were comparable in the other 4 species. The lignin contents of trunk and branchwood were comparable in A. pindrow, C. deodara and P. roxburghii-americana, but showed some variation in the other species. 5 references.

  11. Determination of arsenic, antimony, and bismuth in silicon using 200 keV. cap alpha. -particle backscattering

    Energy Technology Data Exchange (ETDEWEB)

    Hnatowicz, V.; Kvitek, J. (Ceskoslovenska Akademie Ved, Rez. Ustav Jaderne Fyziky); Krejci, P.; Rybka, V. (Tesla, Prague (Czechoslovakia)); Pelikan, L. (Technical University of Prague (Czechoslovakia). Dept. of Microelectronics)

    1982-11-16

    Concentration profiles of As, Sb, and Bi implanted into Si are studied using backscattering of the 200 keV ..cap alpha..-particles. A conventional ion implanter serves as a source of analyzing beam and the scattered particles are detected using a silicon surface barrier detector. Measured projected ranges R/sub P/ of implanted atoms are found to be in satisfactory agreement with theoretical predictions.

  12. Assay and properties of rat yolk sac 25-hydroxyvitamin D/sub 3/ 1. cap alpha. -hydroxylase

    Energy Technology Data Exchange (ETDEWEB)

    Paulson, S.K.; Phelps, M.; DeLuca, H.F.

    1986-11-04

    An in vitro assay has been developed for the rat yolk sac 25-hydroxyvitamin D/sub 3/ 1..cap alpha..-hydroxylase (1..cap alpha..-hydroxylase). The subcellular location and some properties of the enzyme are described. 1,25-Dihydroxyvitamin D/sub 3/ produced from incubations of yolk sac homogenates was extracted, purified by Sephadex LH-20 chromatography and straight- and reverse-phase high-performance liquid chromatography (HPLC), and measured by a competitive binding assay using chick intestinal receptor. The reaction is linear with time for up to 45 min at a substrate concentration of 80 ..mu..M and 4-6 mg/mL microsomal protein. The enzyme, located in the microsomes, requires molecular oxygen and NADPH. Metyrapone (1 x 10/sup -3/ M) was found to inhibit 1-hydroxylation, but a 90% carbon monoxide-10% oxygen atmosphere did not, leaving open the question of involvement of cytochrome P-450. Diphenyl-p-phenylenediamine, a lipid peroxidase inhibitor, inhibited 1..cap alpha..-hydroxylation.

  13. Living with Thalassemias

    Science.gov (United States)

    ... page from the NHLBI on Twitter. Living With Thalassemias Survival and quality of life have improved for people who have moderate or severe thalassemias. This is because: More people are able to ...

  14. The α-thalassemias.

    Science.gov (United States)

    Piel, Frédéric B; Weatherall, David J

    2014-11-13

    More than 100 varieties of α-thalassemia have been identified. Their geographic distribution and the challenges associated with screening, diagnosis, and management suggest that α-thalassemias should have a higher priority on global public health agendas.

  15. Thalassemia: Complications and Treatment

    Science.gov (United States)

    ... on Facebook Tweet Share Compartir If I have thalassemia, how does it affect my body? Since your ... like flu shots and other vaccines. How is thalassemia treated? The type of treatment a person receives ...

  16. Facts about Thalassemia

    Science.gov (United States)

    ... UDC System About Us Blood Disorders Facts About Thalassemia Recommend on Facebook Tweet Share Compartir Did You ... to death. What are the different types of thalassemia? When we talk about different “types” of ...

  17. Beta-globin gene cluster haplotypes and alpha-thalassemia in sickle cell disease patients from Trinidad.

    Science.gov (United States)

    Jones-Lecointe, Altheia; Smith, Erskine; Romana, Marc; Gilbert, Marie-Georges; Charles, Waveney P; Saint-Martin, Christian; Kéclard, Lisiane

    2008-01-01

    In this study, we have determined the frequency of beta(S) haplotypes in 163 sickle cell disease patients from Trinidad. The alpha(3.7) globin gene deletion status was also studied with an observed gene frequency of 0.17. Among the 283 beta(S) chromosomes analyzed, the Benin haplotype was the most prevalent (61.8%) followed by Bantu (17.3%), Senegal (8.5%), Cameroon (3.5%), and Arab-Indian (3.2%), while 5.7% of them were atypical. This beta(S) haplotypes distribution differed from those previously described in other Caribbean islands (Jamaica, Guadeloupe, and Cuba), in agreement with the known involvement of the major colonial powers (Spain, France, and Great Britain) in the slave trade in Trinidad and documented an Indian origin of the beta(S) gene.

  18. Types of thalassemia among patients attending a large university clinic in Kuala Lumpur, Malaysia.

    Science.gov (United States)

    George, E; Li, H J; Fei, Y J; Reese, A L; Baysal, E; Cepreganova, B; Wilson, J B; Gu, L H; Nechtman, J F; Stoming, T A

    1992-01-01

    We have identified the beta-thalassemia mutations in 59 patients with thalassemia major and 47 patients with Hb E-beta-thalassemia, and the deletional and nondeletional alpha-thalassemia determinants in 23 out of 24 patients with Hb H disease. All persons were attending the Haematology Clinic at the National University of Malaysia in Kuala Lumpur (Malaysia). Most patients (76) were of Malay descent, while 52 patients were Chinese, and two came from elsewhere. The most frequently occurring beta-thalassemia alleles among the Malay patients were IVS-I-5 (G----C) and G----A at codon 26 (Hb E), while a few others were present at lower frequencies. The Chinese patients carried the mutation characteristic for Chinese [mainly codons 41/42 (-TTCT) and IVS-II-654 (C----T)]; Malay mutations were not observed among Chinese and Chinese mutations were virtually absent in the Malay patients. The large group of patients with Hb E-beta-thalassemia and different beta-thalassemia alleles offered the opportunity of comparing hematological data; information obtained for patients with Hb E-beta-thalassemia living in other countries was included in this comparison. Twenty-three patients with Hb H disease carried the Southeast Asian (SEA) alpha-thalassemia-1 deletion; 13 had the alpha CS alpha (Constant Spring) nondeletional alpha-thalassemia-2 determinant, while the deletional alpha-thalassemia-2 (-3.7 or -4.2 kb) was present in 10 subjects. The --/alpha CS alpha condition appeared to be the most severe with higher Hb H values. Both deletional and nondeletional types of alpha-thalassemia-2 were seen among Malay and Chinese patients.

  19. Demonstration of. cap alpha. -adrenoceptors in the rabbit bladder base and urethra with /sup 3/H-dihydroergocryptine ligand binding

    Energy Technology Data Exchange (ETDEWEB)

    Larsson, B. (Department of Clinical Pharmacology, University Hospital of Lund, Sweden)

    1983-01-01

    The purpose of this work was to demonstrate the presence of ..cap alpha..-adrenoceptors in a crude membrane preparation made from rabbit bladder base and urethra. This was achieved by radioligand binding studies, using /sup 3/H-dihydro-..cap alpha..-ergocryptine (/sup 3/H-DHE) as the radioligand. The specific binding, i.e. the binding that could be inhibited by 10/sup -5/ M phentolamine, was saturable with 73 fmol /sup 3/H-DHE bound per mg membrane protein. Binding was at steady state after 60 min., and reversible. Rate constants for association and dissocation were 3x10/sup 7/ M/sup -1/ min./sup -1/, and 2x10/sup -2/ min./sup -1/, respectively. A number of compounds were tested for their abilities to compete with /sup 3/H-DHE for the binding sites. The relative affinity of some adrenoceptor agonists was (-)-adrenaline>(-)-noradrenaline much larger than (+-)-isoprenaline. Steroselectivity was shown, since (-)-noradrenaline had 42 times higher affinity than (+)-noradrenaline. Adrenoceptor antagonists inhibited /sup 3/H-DHE binding in the following order of potency: DHE>phentolamine much larger than (+-)-propranolol. The dissociation constant, Ksub(D), for DHE to the binding sites was estimated in three different ways. The constants were derived from saturation, competition, and kinetic studies, and gave Ksub(D) values of 1.1,1.4 and 0.7 nM, respectively. The results suggest that ..cap alpha..-adrenoceptors were labelled by /sup 3/H-DHE in the tissue homogenates.

  20. Evolution of accretion disc flow in cataclysmic variables. 3. Outburst properties of constant and uniform-. cap alpha. model discs

    Energy Technology Data Exchange (ETDEWEB)

    Lin, D.N.C.; Faulkner, J. (Lick Observatory, Santa Cruz, CA (USA); California Univ., Santa Cruz (USA). Board of Studies in Astronomy and Astrophysics); Papaloizou, J. (Queen Mary Coll., London (UK). Dept. of Applied Mathematics)

    1985-01-01

    The investigation of accretion disc models relevant to cataclysmic-variable systems is continued. This paper examines the stability and evolution of some simple accretion disc models in which the viscosity is prescribed by an ad hoc uniform-..cap alpha.. model. It is primarily concerned with systems in which the mass-input rate from the secondary to the disc around the primary is assumed to be constant. However, initial calculations with variable mass-input rates are also performed. The time-dependent visual magnitude light-curves are constructed for cataclysmic binaries with a range of disc size, primary mass, mass-input rate, and magnitude of viscosity.

  1. Genetics Home Reference: beta thalassemia

    Science.gov (United States)

    ... Understand Genetics Home Health Conditions beta thalassemia beta thalassemia Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Beta thalassemia is a blood disorder that reduces the production ...

  2. Avaliação do perfil hematológico de portadores de talassemia alfa provenientes das regiões Sudeste e Nordeste do Brasil Evaluation of alpha thalassemia carriers hematologic profile from Southeast and Northeast Brazilian regions

    Directory of Open Access Journals (Sweden)

    Gislane L. V. Oliveira

    2006-06-01

    Full Text Available A talassemia alfa é uma anemia hereditária resultante da síntese deficiente de cadeias alfa, provocando um excesso relativo de cadeias beta, que vão formar tetrâmeros identificados como hemoglobina H (Hb H no indivíduo adulto. Para direcionar o diagnóstico laboratorial desta anemia, a análise dos índices eritrocitários, a eletroforese em acetato de celulose em pH neutro e a pesquisa de corpos de inclusão de Hb H são essenciais. O objetivo deste estudo foi traçar o perfil hematológico, por meio dos índices eritrocitários, dos portadores de talassemia alfa das regiões Sudeste e Nordeste do Brasil. Foram analisadas 1.010 amostras de sangue periférico após consentimento informado. Os índices eritrocitários como contagem de glóbulos vermelhos (RBC, dosagem de hemoglobina (HGB, hematócrito (HCT, volume corpuscular médio (VCM, hemoglobina corpuscular média (HCM e concentração de hemoglobina corpuscular média (CHCM foram fornecidos por aparelhos automatizados com controle de qualidade interno e externo. Para o diagnóstico de talassemia alfa foram utilizados testes de triagem e complementares para talassemias, como eletroforese em pH neutro e pesquisa de corpos de inclusão de Hb H com coloração de azul cresil brilhante. Comparando-se os valores hematológicos observados nos dois grupos, notou-se que, em ambas as regiões, os índices com valores discrepantes foram os níveis de HGB e HCT, sendo a maior freqüência de variação observada entre as mulheres. Nos portadores do fenótipo alfa talassêmico da região Nordeste, todos os índices eritrocitários estavam abaixo dos valores de normalidade. Estes resultados evidenciam a necessidade de melhor avaliação do perfil hematológico de talassemia alfa em diferentes regiões, considerando-se os interferentes ambientais para um diagnóstico mais preciso.Alpha thalassemia is a hereditary anaemia resulting from deficient synthesis of the alpha chains, causing a relative

  3. Electron double ionization cross section in sodium obtained from K. cap alpha. sup(h) hypersatellite spectra

    Energy Technology Data Exchange (ETDEWEB)

    Lahtinen, J.; Keski-Rahkonen, O. (Laboratory of Physics, Helsinki University of Technology, Espoo, Finland)

    1983-05-01

    The K..cap alpha..sup(h) hypersatellite spectrum of Na metal has been measured in electron excitation with voltages from 4 to 25 kV. The spectrum shows lines with initial K/sup -2/ (K..cap alpha../sub 2/sup(h)) and K/sup -2/L/sup -1/ holes. The energies of these lines as well as the K/sup 2/ binding energy have been determined and compared with theoretical calculations. The intensity of the line group with K/sup -2/L/sup -1/ initial configuration relative to the K/sup -2/ group has been measured and found to be in agreement with simple shake-off calculation. The electron double ionization cross section (EDC) of the K-shell has been determined from both thick and thin target measurements using the method developed by Saijonmaa and Keski-Rahkonen, and found to yield equivalent results. The EDC has also been calculated theoretically using classical and quantum mechanical binary encounter approximations as devised by Saijonmaa. Theory reproduces fairly well the magnitude and the atomic number dependence of the EDC whereas the shape of the EDC-curve as function of energy deviates clearly from observed values.

  4. β-Thalassemia Intermedia: A Bird’s-Eye View

    Directory of Open Access Journals (Sweden)

    Anthony Haddad

    2014-03-01

    Full Text Available Beta-thalassemia is due to a defect in the synthesis of the beta-globin chains, leading to alpha/beta imbalance, ineffective erythropoiesis, and chronic anemia. The spectrum of thalassemias is wide, with one end comprising thalassemia minor, which consists of a mild hypochromic microcytic anemia with no obvious clinical manifestations, while on the other end is thalassemia major, characterized by patients who present in their first years of life with profound anemia and regular transfusion requirements for survival. Along the spectrum lies thalassemia intermedia, a term developed to describe patients with manifestations that are neither mild enough nor severe enough to be classified in the spectrum’s extremes. Over the past decade, our understanding of β-thalassemia intermedia has increased tremendously with regards to molecular information as well as pathophysiology. It is now clear that β-thalassemia intermedia has a clinical presentation as well as complications associated with the disease that are different from those of β-thalassemia major. This review is designed to tackle issues related to β-thalassemia intermedia from the basic definition of the disease to paramedical issues, namely the quality of life in these patients. Genetics and pathophysiology are revisited, as well as the complications specific to this disease. These complications include effects on several organ systems, including the cardiovascular, hepatic, endocrine, renal, brain, and skeletal systems. Extramedullary hematopoiesis is also discussed in this article. Risk factors are highlighted and cutoffs are identified to minimize morbidities in β-thalassemia intermedia. Several treatment modalities are considered by shining a light on the pros and cons of each modality, as well as the role of special pharmacological agents in the progress of the disease and its morbidities. Finally, health-related quality of life is discussed in these patients with a direct comparison

  5. Expression of herpes simplex virus. beta. and. gamma. genes integrated in mammalian cells and their induction by an. cap alpha. gene product

    Energy Technology Data Exchange (ETDEWEB)

    Sandri-Goldin, R.M.; Goldin, A.L.; Holland, L.E.

    1983-11-01

    The proteins of herpes simplex virus type 1 (HSV-1) form three kinetic groups termed ..cap alpha..,..beta..,and ..gamma.., whose synthesis is regulated in a cascade fashion, ..cap alpha.. products are synthesized first during infection, and they are required for synthesis of ..beta.. and ..gamma.. proteins. To examine the expression of several HSV-1 ..beta.. and ..gamma.. genes in the absence of ..cap alpha.. functions, we transferred into mammalian cells a plasmid containing a region of the HSV-1 genome that codes for only ..beta.. and ..gamma.. genes (0.315 to 0.421 map units). The authors found stable integration of at least one copy of the intact plasmid in each cell line. Four HSV-1 transcripts of the ..beta.. and ..gamma.. classes were transcribed constitutively in the cells, including the genes for glycoprotein B and DNA-binding protein. No constitutive synthesis of these two proteins could be demonstrated, however. The integrated HSV-1 genes responded to viral regulatory signals in that they could be induced by infection with HSV-1 mutants resulting in a high level of synthesis of both glycoprotein B and DNA-binding protein. The HSV-1 ..cap alpha.. gene product ICP4 was necessary for this induction, and it was found to be most efficient at a low multiplicity of infection. Functional expression of four genes was demonstrated in that the cell lines complemented infecting HSV-1 temperature-sensitive mutants. The same genes were not available for homologous recombination with infecting virus, however, since no recombinant wild-type virus could be detected. These data demonstrate that HSV-1 ..beta.. and ..gamma.. genes can be transcribed in the absence of ..cap alpha.. functions in mammalian cells, but that they still respond to HSV-1 regulatory signals such as the ..cap alpha.. gene product ICP4.

  6. Hydroxyurea in the management of thalassemia intermedia.

    Science.gov (United States)

    Karimi, Mehran

    2009-01-01

    Hydroxyurea (HU) is an antineoplastic agent that enhances fetal hemoglobin. The clinical significance induced by this compound is well known in sickle cell disease. This clinical significance could also be expected in beta-thalassemia patients. Although studies on beta-thalassemia major patients showed significant results, but these clinical responses are expected to be more in thalassemia intermedia (TI) patients because of lesser alpha/beta globin imbalance. Studies showed that HU therapy in TI patients has significant effects on increasing Hb levels that can cause reducing blood transfusion dependency and transfusion free in some patients, decreasing skeletal deformities and splenomegaly and increasing energy state. So HU therapy could be a useful alternative to blood transfusion in some TI patients.

  7. mRNA expression of iron regulatory genes in beta-thalassemia intermedia and beta-thalassemia major mouse models.

    Science.gov (United States)

    Weizer-Stern, Orly; Adamsky, Konstantin; Amariglio, Ninette; Rachmilewitz, Eliezer; Breda, Laura; Rivella, Stefano; Rechavi, Gideon

    2006-07-01

    beta-Thalassemia is an inherited anemia in which synthesis of the hemoglobin beta-chain is decreased. The excess unmatched alpha-globin chains accumulate in the growing erythroid precursors, causing their premature death (ineffective erythropoiesis). Clinical features of beta-thalassemia include variably severe anemia and iron accumulation due to increased intestinal iron absorption. The most anemic patients require regular blood transfusions, which exacerbate their iron overload and result in damage to vital organs. The hepatic peptide hepcidin, a key regulator of iron metabolism in mammals, was recently found to be low in the urine of beta-thalassemia patients, compared with healthy controls, despite their iron overload. In our work, we measured by RQ-PCR the liver mRNA expression of hepcidin and other iron regulatory genes in beta-thalassemia major mouse model (C57Bl/6 Hbb(th3/th3)), and compared it with beta-thalassemia intermedia mouse model (C57Bl/6 Hbb(th3/+)) and control mice. We found decreased expression of hepcidin and TfR2 and increased expression of TfR1 and NGAL in the beta-thalassemia mouse models, compared with the control mice. Significant down-regulation of hepcidin expression in beta-thalassemia major, despite iron overload, might explain the increased iron absorption typically observed in thalassemia.

  8. Characteristics of the photelectromagnetic effect and properties of recombination centers in germanium single crystals irradiated with. cap alpha. particles

    Energy Technology Data Exchange (ETDEWEB)

    Babichenko, V.S.; Kikoin, L.I.; Lazarev, S.D.; Rzhanov, A.E.; Filippov, V.I.

    1984-01-01

    The spatial distribution of defects created in Ge crystals by irradiation with 40-MeV ..cap alpha.. particles was investigated. The distribution of the defects acting as recombination centers had a decisive influence on the diffusion-recombination processes in this semiconductor. The carrier-capture cross section of the recombination centers (sigmaapprox.10/sup -15/ cm/sup 2/) was determined. A concept of a recombination wall, which appeared in the region of a maximum of the radiation defect concentration, was introduced. The experimental data were compared with theoretical representations. This comparison demonstrated that an investigation of the photoelectromagnetic effect could give information both on the nature of the spatial distribution of radiation defects and on the recombination parameters of an irradiated semiconductor.

  9. Special features of photoelectromagnetic effect and properties of recombination centers in germanium single crystals irradiated by. cap alpha. particles

    Energy Technology Data Exchange (ETDEWEB)

    Babichenko, V.S.; Kikoin, L.I.; Lazarev, S.D.; Rzhanov, A.E.; Filippov, V.I.

    1984-01-01

    Results of studies on a spatial distribution of defects arising in Ge crystals following ..cap alpha..-particle (40 MeV) irradiation are given. The distribution of defects playing the role of recombination centres is shown to produce the definite effect on diffusion-recombination processes in semiconductors. The carrier capture cross section on recombination centres is determined to be sigma approximately 10/sup -15/ cm/sup -2/. A representation of recombination wall appearing in the vicinity of radiation defect concentration peak is introduced. The experimental data are compared with the developed theoretical representations. It is shown that studies on the photoelectromagnetic effect can give information both on the pattern of radiation defect spatial distribution and recombination parameters of irradiated semiconductors.

  10. Imaging features of thalassemia

    Energy Technology Data Exchange (ETDEWEB)

    Tunaci, M.; Tunaci, A.; Engin, G.; Oezkorkmaz, B.; Acunas, G.; Acunas, B. [Dept. of Radiology, Istanbul Univ. (Turkey); Dincol, G. [Dept. of Internal Medicine, Istanbul Univ. (Turkey)

    1999-07-01

    Thalassemia is a kind of chronic, inherited, microcytic anemia characterized by defective hemoglobin synthesis and ineffective erythropoiesis. In all thalassemias clinical features that result from anemia, transfusional, and absorptive iron overload are similar but vary in severity. The radiographic features of {beta}-thalassemia are due in large part to marrow hyperplasia. Markedly expanded marrow space lead to various skeletal manifestations including spine, skull, facial bones, and ribs. Extramedullary hematopoiesis (ExmH), hemosiderosis, and cholelithiasis are among the non-skeletal manifestations of thalassemia. The skeletal X-ray findings show characteristics of chronic overactivity of the marrow. In this article both skeletal and non-skeletal manifestations of thalassemia are discussed with an overview of X-ray findings, including MRI and CT findings. (orig.)

  11. Effects of the. cap alpha. -adrenoceptor antagonists phentolamine, phenoxybenzamine, and Idazoxan on sympathetic blood flow control in the periodontal ligament of the cat

    Energy Technology Data Exchange (ETDEWEB)

    Edwall, B.; Gazelius, B.

    1988-01-01

    Blood flow changes in the periodontal ligament (PDL) were measured indirectly by monitoring the local clearance of /sup 125/I/sup -/ during electric sympathetic nerve stimulation or close intra-arterial infusions of either noradrenaline (NA) or adrenaline (ADR) before and after administration of phentolamine (PA), phenoxybenzamine (PBZ) or Idazoxan (RX). At the doses used in the present study, PA was the only antagonist that significantly reduced the blood flow decrease seen on activation of sympathetic fibers, although PBZ also reduced this response. Idazoxan, however, did not induce the consistent effect on blood flow decreases seen on sympathetic activation. All three ..cap alpha..-adrenoceptor antagonists almost abolished the effects of exogenously administered NA and ADR. The results suggest the presence of functional post-junctional adrenoceptors of both the ..cap alpha.. 1 and ..cap alpha.. 2 subtypes in the sympathetic regulation of the blood flow in the PDL of the cat. A component of the response elicited by electrical sympathetic stimulation appeared to be resistant to ..cap alpha..-adrenoceptor blockade. Administration of guanethidine (which inhibits further release of NA and neuropeptide Y) after PA abolished this residual sympathetic response. 32 refs.

  12. Development of a radioiodinated ligand for characterising. cap alpha. /sub 1/-adrenoceptors. [Pentolamine and 2 BETA-(4-hydroxyphenyl)-ethylaminomethyl)-tetralone

    Energy Technology Data Exchange (ETDEWEB)

    Adams, A.; Jarrott, B.

    1982-03-15

    Two ..cap alpha..-adrenoceptor antagonists, phentolamine and 2-(..beta..-(4-hydroxyphenyl)-ethylaminomethyl)-tetralone (BE 2254) which are phenolic derivatives were radioiodinated after chloramine-T oxidation of Na/sup 125/I and the labelled material isolated by chromatography. /sup 125/I-Phentolamine does not bind selectively to ..cap alpha..-adrenoceptors in guinea pig brain whereas the /sup 125/I-BE 2254 derivative binds rapidly, reversibly and with high affinity to these receptors with a K/sub d/ of 230 pM. At low concentrations of /sup 125/I-BE 2254 (< 100 pM) approx. 90% of the bound radioligand is specifically bound and under these conditions drug displacement studies show that the ligand binds predominantly to the ..cap alpha../sub 1/ subclass of adrenoceptors. Binding measurements to kidney and smooth muscle membrane preparations indicate that /sup 125/I-BE 2254 may also be a useful tool in the study of ..cap alpha..-adrenoceptors in peripheral tissues. The high specific activity of /sup 125/I-BE 2254 permits the use of minimal quantities of membrane material for receptor assay and ligand displacement measurements, e.g. 250 ..mu..g per assay tube, and this provides a significant advantage over the use of existing radioligands such as /sup 3/H-prazosin which requires approx. 40 times as much tissue.

  13. Radioimmunological determination of 5. cap alpha. -pregnane-3,20-dione in the peripheral venous blood of pregnant women showing pathological estriol values and/or HPL values or gestosis, on the basis of the gestational age. Radioimmunologische Bestimmung des 5. cap alpha. -Pregnan-3,20-dion im peripheren Venenblut schwangerer Frauen einer Gruppe mit pathologischen Oestriol- bzw. HPL-Werten und einer Gestosegruppe in Abhaengigkeit vom Gestationsalter

    Energy Technology Data Exchange (ETDEWEB)

    Klemm-Wolfgramm, E.

    1984-01-01

    A modified method of extraction and radioimmunological determination (iodine-125) is described, designed to monitor the concentrations of 5..cap alpha..-pregnandione (5..cap alpha..-DHP) in patients showing a pathological course of pregnancy and to examine the role of 5..cap alpha..-DHP blood levels in the development of gestosis. In this study, a control group was compared with two patient groups showing either (a) gestosis or (b) reduced levels of estriol and/or HPL. (1) In gestosis, the levels of 5..cap alpha..-DHP showed significant reductions that were proportionate to the degree of the disease, whereas decreases in these hormone levels were only observed to a minor extent in connection with pathological values of estriol and/or HPL. (2) The age of the patient had no influence on the hormone concentrations. (3) The increases in 5..cap alpha..-DHP seen in multiparae were only slight and did not attain any statistical significance. (4) No links were established between the concentrations of HPL and 5..cap alpha..-DHP in the maternal plasma and the development of the fetus. (5) Significantly reduced values of 5..cap alpha..-DHP were determined in mothers showing disorders of fetoplacental function (birth weights between 2500 and 3500 g) or gestosis (birth weights above 3500 g). (6) There were no relationships between the maternal serum levels of estriol, HPL and 5..cap alpha..-DHP and the sex of the fetus. (TRV).

  14. Microautoradiographic studies on distribution of 5. cap alpha. -dihydrotestosterone, cyproterone acetate and oestradiol-17. beta. in human prostatic hyperplasia tissue transplanted to juvenile rats

    Energy Technology Data Exchange (ETDEWEB)

    Ruberg, I.; Neumann, F. (Research Laboratory of Schering AG, Berlin West and Bergkamen, FRG); Senge, Th. (Marinenhospital Herne, Clinic of Urology of the Ruhr-University Bochum, FRG)

    1982-01-01

    While maintaining the actual conditions prevailing in benign prostatic hyperplasia (BHP) in man, transplantation of BPH tissue to newborn rats proved a suitable model for examining the distribution of sexual hormones in different tissue compartments of BPH. In combination with the microautoradiographic method, it was possible to demonstrate the residence of the radioactive androgen 5..cap alpha..-=dihydrotestosterone (5..cap alpha..- DHT), the antiandrogen cyproterone acetate (CA) and the oestrogen oestradiol-17..beta..(E/sub 2/) in the epithelium and/or stroma of human BPH tissue. Quantitative evaluation in the form of a point per area count on photographic pictures yielded a silver grain distribution ratio in epithelium and stroma of 1.3:1 and 1.5:1 for epithelium to stroma after administration of (/sup 3/H)5..cap alpha..-DHT and (/sup 3/H)CA administration respectively and 0.5:1 after (/sup 3/H)E/sub 2/. The high tracer recovery rate throughout the stroma following E/sub 2/ administration supports the current view that the stromal proliferation is attributable mainly to oestrogen influences. The relatively high silver particle proportion throughout the stroma following 5..cap alpha..-DHT administration corroborates recent findings which suggest that the exclusive androgen dependency of the glandular epithelium can only be considered in conjunction with an active metabolization of androgens in the stroma. The correspondence in the distribution of the radioactive tracer after (/sup 3/H)5..cap alpha..-DHT and (/sup 3/H)CA administration both in the epithelium and stroma suggests that an antagonism may also exist in the stroma.

  15. What Causes Thalassemias?

    Science.gov (United States)

    ... percent chance of inheriting two normal genes (no anemia), a 50 percent chance of inheriting one altered gene and one normal gene (beta thalassemia ... INDEX ACCESSIBILITY PRIVACY STATEMENT FOIA NO FEAR ACT OIG ...

  16. Laboratory diagnosis of thalassemia.

    Science.gov (United States)

    Brancaleoni, V; Di Pierro, E; Motta, I; Cappellini, M D

    2016-05-01

    The thalassemias can be defined as α- or β-thalassemias depending on the defective globin chain and on the underlying molecular defects. The recognition of carriers is possible by hematological tests. Both α- and β-thalassemia carriers (heterozygotes) present with microcytic hypochromic parameters with or without mild anemia. Red cell indices and morphology followed by separation and measurement of Hb fractions are the basis for identification of carriers. In addition, iron status should be ascertained by ferritin or zinc protoporphyrin measurements and the iron/total iron-binding capacity/saturation index. Mean corpuscular volume and mean corpuscular hemoglobin are markedly reduced (mean corpuscular volume: 60-70 fl; MCH: 19-23 pg) in β-thalassemia carriers, whereas a slight to relevant reduction is usually observed in α-carriers. HbA2 determination is the most decisive test for β-carrier detection although it can be disturbed by the presence of δ-thalassemia defects. In α-thalassemia, HbA2 can be lower than normal and it assumes significant value when iron deficiency is excluded. Several algorithms have been introduced to discriminate from thalassemia carriers and subjects with iron-deficient anemia; because the only discriminating parameter is the red cell counts, these formulas must be used consciously. Molecular analysis is not required to confirm the diagnosis of β-carrier, but it is necessary to confirm the α-thalassemia carrier status. The molecular diagnosis is essential to predict severe transfusion-dependent and intermediate-to-mild non-transfusion-dependent cases. DNA analysis on chorionic villi is the approach for prenatal diagnosis and the methods are the same used for mutations detection, according to the laboratory facilities and expertise.

  17. Drosophila casein kinase I alpha regulates homolog pairing and genome organization by modulating condensin II subunit Cap-H2 levels.

    Directory of Open Access Journals (Sweden)

    Huy Q Nguyen

    Full Text Available The spatial organization of chromosomes within interphase nuclei is important for gene expression and epigenetic inheritance. Although the extent of physical interaction between chromosomes and their degree of compaction varies during development and between different cell-types, it is unclear how regulation of chromosome interactions and compaction relate to spatial organization of genomes. Drosophila is an excellent model system for studying chromosomal interactions including homolog pairing. Recent work has shown that condensin II governs both interphase chromosome compaction and homolog pairing and condensin II activity is controlled by the turnover of its regulatory subunit Cap-H2. Specifically, Cap-H2 is a target of the SCFSlimb E3 ubiquitin-ligase which down-regulates Cap-H2 in order to maintain homologous chromosome pairing, chromosome length and proper nuclear organization. Here, we identify Casein Kinase I alpha (CK1α as an additional negative-regulator of Cap-H2. CK1α-depletion stabilizes Cap-H2 protein and results in an accumulation of Cap-H2 on chromosomes. Similar to Slimb mutation, CK1α depletion in cultured cells, larval salivary gland, and nurse cells results in several condensin II-dependent phenotypes including dispersal of centromeres, interphase chromosome compaction, and chromosome unpairing. Moreover, CK1α loss-of-function mutations dominantly suppress condensin II mutant phenotypes in vivo. Thus, CK1α facilitates Cap-H2 destruction and modulates nuclear organization by attenuating chromatin localized Cap-H2 protein.

  18. Drosophila Casein Kinase I Alpha Regulates Homolog Pairing and Genome Organization by Modulating Condensin II Subunit Cap-H2 Levels

    Science.gov (United States)

    Nguyen, Huy Q.; Nye, Jonathan; Buster, Daniel W.; Klebba, Joseph E.; Rogers, Gregory C.; Bosco, Giovanni

    2015-01-01

    The spatial organization of chromosomes within interphase nuclei is important for gene expression and epigenetic inheritance. Although the extent of physical interaction between chromosomes and their degree of compaction varies during development and between different cell-types, it is unclear how regulation of chromosome interactions and compaction relate to spatial organization of genomes. Drosophila is an excellent model system for studying chromosomal interactions including homolog pairing. Recent work has shown that condensin II governs both interphase chromosome compaction and homolog pairing and condensin II activity is controlled by the turnover of its regulatory subunit Cap-H2. Specifically, Cap-H2 is a target of the SCFSlimb E3 ubiquitin-ligase which down-regulates Cap-H2 in order to maintain homologous chromosome pairing, chromosome length and proper nuclear organization. Here, we identify Casein Kinase I alpha (CK1α) as an additional negative-regulator of Cap-H2. CK1α-depletion stabilizes Cap-H2 protein and results in an accumulation of Cap-H2 on chromosomes. Similar to Slimb mutation, CK1α depletion in cultured cells, larval salivary gland, and nurse cells results in several condensin II-dependent phenotypes including dispersal of centromeres, interphase chromosome compaction, and chromosome unpairing. Moreover, CK1α loss-of-function mutations dominantly suppress condensin II mutant phenotypes in vivo. Thus, CK1α facilitates Cap-H2 destruction and modulates nuclear organization by attenuating chromatin localized Cap-H2 protein. PMID:25723539

  19. Molecular basis of asymptomatic beta-thalassemia major in an African American individual.

    Science.gov (United States)

    Ballas, S K; Cai, S P; Gabuzda, T; Chehab, F F

    1997-03-17

    The beta-thalassemia syndromes are a heterogeneous group of genetic disorders characterized by reduced or absent expression of the beta-globin gene. To date, over 300 beta-thalassemia alleles have been characterized in or around the beta-globin region. Thalassemia major is severe anemia necessitating chronic blood transfusions, splenectomy, iron chelation therapy, and bone marrow transplantation. Usually thalassemia major results from homozygosity or compound heterozygosity for severe betaO- and/or beta+-thalassemia mutations. Thalassemia intermedia is a clinical diagnosis that describes a symptomatic but less severe condition than beta-thalassemia major. beta-thalassemia intermedia may arise from several different combinations of alpha- and/or beta-thalassemia mutations. Heterozygous beta-thalassemia is typically characterized by a mild microcytic hypochromic anemia without any significant clinical implications. In this report, we describe a 63-year-old Africian American woman with asymptomatic homozygous beta-thalassemia, who seems to carry 2 copies of the -29 mutation in the promoter region of the beta-globin gene. Her elevated hemoglobin F level of 83% was associated with heterozygosity for the Xmn I polymorphism upstream of the Ggamma-globin gene. Southern blot analysis at the alpha-globin locus did not show any deletion that would account for the mildness of her phenotype. Therefore, homozygosity for the -29 mutation along with the Xmn I polymorphism appears to confer an extremely mild beta-thalassemia phenotype. This observation has important implications in the prenatal diagnosis and genetic counseling of families segregating this type of genetic defect.

  20. New mathematical formula for differentiating thalassemia trait and iron deficiency anemia in thalassemia prevalent area: a study in healthy school-age children.

    Science.gov (United States)

    Sirachainan, Nongnuch; Iamsirirak, Pornchanok; Charoenkwan, Pimlak; Kadegasem, Praguywan; Wongwerawattanakoon, Pakawan; Sasanakul, Werasak; Chansatitporn, Natkamol; Chuansumrit, Ampaiwan

    2014-01-01

    Iron deficiency anemia (IDA) and thalassemias are common diseases especially in the Mediterranean, Middle East and Asian regions. Both conditions show the same clinical findings of hypochromic and microcytic red blood cells. Although previous studies have devised mathematical formulae to differentiate between these two conditions, the prevalence of alpha- and beta-thalassemias among the affected populations may undermine the accuracy of these formulae. This study generated a new formula that was able to differentiate IDA and thalassemia traits and to determine the incidence rates of IDA and thalassemia traits. A total of 345 healthy Thai children with a mean age (+/- SD) of 11.3 (+/- 1.7) years were enrolled. Complete blood count, iron status, hemoglobin typing and DNA for alpha-1 thalassemia identification were investigated. Discriminant analysis was used to create a new mathematical formula containing significant variables to differentiate between IDA and thalassemia traits. The new formula of (1.5 Hb-0.05 MCV >14) had a receiver operator characteristic curve of 0.92 in differentiating thalassemia traits from IDA, with sensitivity and specificity of 84.6 and 87.5%, respectively. The incidence of IDA and thalassemia traits in the study group was 12% and 32%, respectively. This formula should be useful as a screening tool to differentiate between these two conditions.

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

    Science.gov (United States)

    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.

  2. Association of elongation factor 1 alpha and ribosomal protein L3 with the proline-rich region of yeast adenylyl cyclase-associated protein CAP.

    Science.gov (United States)

    Yanagihara, C; Shinkai, M; Kariya, K; Yamawaki-Kataoka, Y; Hu, C D; Masuda, T; Kataoka, T

    1997-03-17

    CAP is a multifunctional protein; the N-terminal region binds adenylyl cyclase and controls its response to Ras while the C-terminal region is involved in cytoskeletal regulation. In between the two regions, CAP possesses two proline-rich segments, P1 and P2, resembling a consensus sequence for binding SH3 domains. We have identified two yeast proteins with molecular sizes of 48 and 46 kDa associated specifically with P2. Determination of partial protein sequences demonstrated that the 48-kDa and 46-kDa proteins correspond to EF1 alpha and rL3, respectively, neither of which contains any SH3-domain-like sequence. Deletion of P2 from CAP resulted in loss of the activity to bind the two proteins either in vivo or in vitro. Yeast cells whose chromosomal CAP was replaced by the P2-deletion mutant displayed an abnormal phenotype represented by dissociated localizations of CAP and F-actin, which were colocalized in wild-type cells. These results suggest that these associations may have functional significance.

  3. Beta-thalassemia

    Directory of Open Access Journals (Sweden)

    Origa Raffaella

    2010-05-01

    Full Text Available Abstract Beta-thalassemias are a group of hereditary blood disorders characterized by anomalies in the synthesis of the beta chains of hemoglobin resulting in variable phenotypes ranging from severe anemia to clinically asymptomatic individuals. The total annual incidence of symptomatic individuals is estimated at 1 in 100,000 throughout the world and 1 in 10,000 people in the European Union. Three main forms have been described: thalassemia major, thalassemia intermedia and thalassemia minor. Individuals with thalassemia major usually present within the first two years of life with severe anemia, requiring regular red blood cell (RBC transfusions. Findings in untreated or poorly transfused individuals with thalassemia major, as seen in some developing countries, are growth retardation, pallor, jaundice, poor musculature, hepatosplenomegaly, leg ulcers, development of masses from extramedullary hematopoiesis, and skeletal changes that result from expansion of the bone marrow. Regular transfusion therapy leads to iron overload-related complications including endocrine complication (growth retardation, failure of sexual maturation, diabetes mellitus, and insufficiency of the parathyroid, thyroid, pituitary, and less commonly, adrenal glands, dilated myocardiopathy, liver fibrosis and cirrhosis. Patients with thalassemia intermedia present later in life with moderate anemia and do not require regular transfusions. Main clinical features in these patients are hypertrophy of erythroid marrow with medullary and extramedullary hematopoiesis and its complications (osteoporosis, masses of erythropoietic tissue that primarily affect the spleen, liver, lymph nodes, chest and spine, and bone deformities and typical facial changes, gallstones, painful leg ulcers and increased predisposition to thrombosis. Thalassemia minor is clinically asymptomatic but some subjects may have moderate anemia. Beta-thalassemias are caused by point mutations or, more rarely

  4. Beta-thalassemia.

    Science.gov (United States)

    Galanello, Renzo; Origa, Raffaella

    2010-05-21

    Beta-thalassemias are a group of hereditary blood disorders characterized by anomalies in the synthesis of the beta chains of hemoglobin resulting in variable phenotypes ranging from severe anemia to clinically asymptomatic individuals. The total annual incidence of symptomatic individuals is estimated at 1 in 100,000 throughout the world and 1 in 10,000 people in the European Union. Three main forms have been described: thalassemia major, thalassemia intermedia and thalassemia minor. Individuals with thalassemia major usually present within the first two years of life with severe anemia, requiring regular red blood cell (RBC) transfusions. Findings in untreated or poorly transfused individuals with thalassemia major, as seen in some developing countries, are growth retardation, pallor, jaundice, poor musculature, hepatosplenomegaly, leg ulcers, development of masses from extramedullary hematopoiesis, and skeletal changes that result from expansion of the bone marrow. Regular transfusion therapy leads to iron overload-related complications including endocrine complication (growth retardation, failure of sexual maturation, diabetes mellitus, and insufficiency of the parathyroid, thyroid, pituitary, and less commonly, adrenal glands), dilated myocardiopathy, liver fibrosis and cirrhosis). Patients with thalassemia intermedia present later in life with moderate anemia and do not require regular transfusions. Main clinical features in these patients are hypertrophy of erythroid marrow with medullary and extramedullary hematopoiesis and its complications (osteoporosis, masses of erythropoietic tissue that primarily affect the spleen, liver, lymph nodes, chest and spine, and bone deformities and typical facial changes), gallstones, painful leg ulcers and increased predisposition to thrombosis. Thalassemia minor is clinically asymptomatic but some subjects may have moderate anemia. Beta-thalassemias are caused by point mutations or, more rarely, deletions in the beta

  5. β-Thalassemia hijacking ineffective erythropoietin and iron overload: Two case reports and a review of literature

    OpenAIRE

    2014-01-01

    Thalassemia is a rare, complex disease, representing a group of disorders of hemoglobin synthesis that are characterized by reduced synthesis of either the alpha-globin or β-globin chains of the hemoglobin molecule. Defective synthesis of β-globin resulting from a variety of molecular defects causes β-thalassemia. Thalassemia is an autosomal recessive disorder, which requires prompt diagnosis and an appropriate treatment. Thorough clinical, radiographic and laboratory assessment helps in diag...

  6. Internode length in Pisum. Gene na may block gibberellin synthesis between ent-7. cap alpha. -hydroxykaurenoic acid and biggerellin A/sub 12/-aldehyde. [Pisum sativum

    Energy Technology Data Exchange (ETDEWEB)

    Ingram, T.J.; Reid, J.B.

    1987-04-01

    The elongation response of the gibberellin (GA) deficient genotypes na, ls, and lh of peas (Pisum sativum L.) to a range of GA-precursors was examined. Plants possessing gene na did not respond to precursors in the GA biosynthetic pathway prior to GA/sub 12/-aldehyde. In contrast, plants possessing lh and ls responded as well as wild-type plants (dwarfed with AMO-1618) to these compounds. The results suggest that GA biosynthesis is blocked prior to ent-kaurene in the lh and ls mutants and between ent-7..cap alpha..-hydroxykaurenoic acid and GA/sub 12/-aldehyde in the na mutant. Feeds of ent(/sup 3/H)kaurenoic acid and (/sup 2/H)GA/sub 12/-aldehyde to a range of genotypes supported the above conclusions. The na line WL1766 was shown by gas chromatography-mass spectrometry (GC-MS) to metabolize(/sup 2/H)GA/sub 12/-aldehyde to a number of (/sup 2/H)C/sub 19/-GAs including GA/sub 1/. However, there was no indication in na genotypes for the metabolism of ent-(/sup 3/H)kaurenoic acid to these GAs. In contrast, the expanding shoot tissue of all Na genotypes examined metabolized ent-(/sup 3/H)kaurenoic acid to radioactive compounds that co-chromatographed with GA/sub 1/, GA/sub 8/, GA/sub 20/, and GA/sub 29/. However, insufficient material was present for unequivocal identification of the metabolites. The radioactive profiles from HPLC of extracts of the node treated with ent-(/sup 3/H)kaurenoic acid were similar for both Na and na plants and contained ent-16..cap alpha..,17-dihydroxykaurenoic acid and ent-6..cap alpha..,7..cap alpha..,16..beta..,17-tetrahydroxykaurenoic acid (both characterized by GC-MS), suggesting that the metabolites arose from side branches of the main GA-biosynthetic pathway. Thus, both Na and na plants appear capable of ent-7..cap alpha..-hydroxylation.

  7. 3种少见α地中海贫血点突变杂合取合予的临床特征%Clinical Characteristics of Heterozygote and Double Heterozygote of Three Rare Mutations in alpha- Thalassemia

    Institute of Scientific and Technical Information of China (English)

    许涓涓; 丘小霞; 杜娟; 李萌; 黄萍丽; 李娇

    2014-01-01

    Objective:To examine clinical characteristics of heterozygote and double heterozygote of three rare mutations [Hb Constants Spring(Hb CS),Hb Westmead(Hb WS) and Hb Quong Sze(Hb QS)] among alpha-thalassemia patients in Guangxi province, China. Methods:135 alpha-thalassemia patients, and 40 controls, were included in this study. Routine examination of blood and hemoglobin electrophoresis were performed. The alpha-thalassemia mutations were detected using Gap-PCR and reverse dot-blotting. Results:There were no clinical symptoms in three heterozygote groups and the double heterozygote group of αCSα/αWSα. MCV and MCH in the heterozygote group of Hb QS were significantly lower than those in other heterozygote groups (Hb CS and Hb WS) (P<0.05). However,there was mild clinical symptoms in the double heterozygote group of αCSα/αQSα, while MCV and MCH were also significantly lower than those in other heterozygote groups (Hb CS and Hb WS) (P<0.05). Conclusions: The heterozygote Hb CS,heterozygote Hb WS and double heterozygoteαCSα/αWSαare the silent carrier in clinical manifestations, the heterozygote Hb QS is the thalassemia trait, and the double heterozygote αCSα/αQSα is similar to the HbH disease. It is important to note this variability of clinical manifestations of those double heterozygotes in genetic consultation.%目的:了解3种少见α地中海贫血点突变[血红蛋白Constants Spring (Hb CS),血红蛋白Westmead(Hb WS)和血红蛋白Quong Sze(Hb QS)]杂合子与双重杂合子的临床特征。方法:收集135例上述3种α-地中海贫血点突变的杂合子与双重杂合子患者和正常对照男女各20例,进行血常规参数分析、血红蛋白分析、等位基因特异性寡核苷酸探针反向斑点杂交方法(RDB)和多重跨越断裂点聚合酶链反应(PCR)方法检测基因型。结果:杂合子组、Hb CS和Hb WS双重杂合子(αCSα/αWSα)组均无临床表现,但Hb QS杂合子(αQS

  8. Isolation and characterization of cDNA encoding the alpha subunit of Cap Z(36/32), an actin-capping protein from the Z line of skeletal muscle.

    OpenAIRE

    Casella, J F; Casella, S J; Hollands, J. A.; Caldwell, J E; Cooper, J A

    1989-01-01

    cDNA encoding the alpha chain of Cap Z has been isolated by screening a lambda gt11 library with affinity-purified antibodies. A single cDNA insert (designated CE2) of 2153 base pairs (bp) contains an open reading frame of 836 bp, which is incomplete at its 5' end. The technique of "rapid amplification of cDNA ends" has been used to extend the 5' end of this open reading frame to a potential transcription initiation site that is preceded by 320 bp of an apparently untranslated region. The pro...

  9. SCREENING CORD BLOOD FOR HEMOGLOBINOPATHIES AND THALASSEMIA BY HPLC

    NARCIS (Netherlands)

    VANDERDIJS, FPL; VANDENBERG, GA; SCHERMER, JG; MUSKIET, FD; LANDMAN, H; MUSKIET, FAJ

    1992-01-01

    We evaluated the use of an HPLC method for screening hemoglobins in cord blood. We studied the genotype frequencies of the structural hemoglobin variants HbS and HbC and the synthesis variants alpha- and beta+-thalassemia in babies born on Curacao. During three months, 67.2% of all (748) newborns we

  10. 1. cap alpha. ,25-Dihydroxyvitamin D/sub 3/ inhibits. gamma. -interferon synthesis by normal human peripheral blood lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Reichel, H.; Koeffler, H.P.; Tobler, A.; Norman, A.W.

    1987-05-01

    1..cap alpha..,25-Dihydroxyvitamin D/sub 3/ (1,25-(OH)/sub 2/D/sub 3/), the biologically active metabolite of vitamin D/sub 3/, inhibited synthesis of ..gamma..-interferon (IFN-..gamma..) by phytohemagglutinin-activated peripheral blood lymphocytes (PBLs). A significant reduction of IFN-..gamma.. protein levels in PBL culture medium was achieved with a physiologic 1,25-(OH)/sub 2/D/sub 3/ concentration, 1,25-(OH)/sub 2/D/sub 3/ also inhibited accumulation of IFN-..gamma.. mRNA in activated PBLs in a dose-dependent fashion. The ability of 1,25-(OH)/sub 2/D/sub 3/ to modulate IFN-..gamma.. protein synthesis was unaltered in the presence of high concentrations of recombinant human interleukin 2. The suppression of IFN-..gamma.. synthesis by PBLs was specific for 1,25-(OH)/sub 2/D/sub 3/; the potencies of other vitamin D/sub 3/ metabolites were correlated with their affinities for the cellular 1,25-(OH)/sub 2/D/sub 3/ receptor. The time course of 1,25-(OH)/sub 2/D/sub 3/ receptor expression in phytohemagglutinin-activated PBLs was correlated with the time course of 1,25-(OH)/sub 2/D/sub 3/-mediated inhibition of IFN-..gamma.. synthesis. Finally, the authors examined the effects of 1,25-(OH)/sub 2/D/sub 3/ on the constitutive IFN-..gamma.. production by two human T-lymphocyte lines transformed by human T-lymphotropic virus type I. The cell lines were established from a normal donor (cell line S-LB1) and from a patient with vitamin D-dependent rickets type 2 (cell line Ab-VDR). IFN-..gamma.. synthesis by S-LB1 cells was inhibited in a dose-dependent fashion by 1,25-(OH)/sub 2/D/sub 3/, whereas IFN-..gamma.. synthesis by Ab-VDR cells was not altered by 1,25-(OH)/sub 2/D/sub 3/. The data presented in this study provide evidence for a role of 1,25-(OH)/sub 2/D/sub 3/ in immunoregulation.

  11. Beta Thalassemia (For Parents)

    Science.gov (United States)

    ... had their spleens removed. Slower growth rates. The anemia resulting from beta thalassemia can cause children to grow more slowly and also can lead ... boost production of new red blood cells. Some children with moderate anemia may require an occasional blood transfusion , particularly after ...

  12. Structure-function relationships in the Na,K-ATPase. cap alpha. subunit: site-directed mutagenesis of glutamine-111 to arginine and asparagine-122 to aspartic acid generates a ouabain-resistant enzyme

    Energy Technology Data Exchange (ETDEWEB)

    Price, E.M.; Lingrel, J.B.

    1988-11-01

    Na,K-ATPases from various species differ greatly in their sensitivity to cardiac glycosides such as ouabain. The sheep and human enzymes are a thousand times more sensitive than the corresponding ones from rat and mouse. To define the region of the ..cap alpha..1 subunit responsible for this differential sensitivity, chimeric cDNAs of sheep and rat were constructed and expressed in ouabain-sensitive HeLa cells. The construct containing the amino-terminal half of the rat ..cap alpha..1 subunit coding region and carboxyl-terminal half of the sheep conferred the ouabain-resistant phenotype to HeLa cells while the reverse construct did not. This indicates that the determinants involved in ouabain sensitivity are located in the amino-terminal half of the Na,K-ATPase ..cap alpha.. subunit. By use of site-directed mutagenesis, the amino acid sequence of the first extracellular domain (H1-H2) of the sheep ..cap alpha..1 subunit was changed to that of the rat. When expressed in HeLa cells, this mutated sheep ..cap alpha..1 construct, like the rat/sheep chimera, was able to confer ouabain resistance to these cells. Furthermore, similar results were observed when HeLa cells were transfected with a sheep ..cap alpha..1 cDNA containing only two amino acid substitutions. The resistant cells, whether transfected with the rat ..cap alpha..1 cDNA, the rat/sheep chimera, or the mutant sheep ..cap alpha..1 cDNAs, exhibited identical biochemical characteristics including ouabain-inhibitable cell growth, /sup 86/Rb/sup +/ uptake, and Na,K-ATPase activity. These results demonstrate that the presence of arginine and aspartic acid on the amino end and carboxyl end, respectively, of the H1-H2 extracellular domain of the Na,K-ATPase ..cap alpha.. subunit together is responsible for the ouabain-resistant character of the rat enzyme and the corresponding residues in the sheep ..cap alpha..1 subunit (glutamine and asparagine) are somehow involved in ouabain binding.

  13. Associations between a+-thalassemia and Plasmodium falciparum malarial infection in northeastern Tanzania

    DEFF Research Database (Denmark)

    Enevold, Anders; Alifrangis, Michael; Sanchez, Juan J

    2007-01-01

    BACKGROUND: The 2 most common hemoglobinopathies, sickle cell trait and alpha (+)-thalassemia, confer partial resistance to fatal forms of malaria, but the molecular basis for this protection is still not understood. Examination of the relationship between these traits and malaria transmission......) to 45%-55% in low-altitude villages (sickle...... cell trait was lower than that of alpha (+)-thalassemia (range, 0%-14%) and was significantly associated with village altitude only (P=.011). STR allele frequencies were similar in all villages. CONCLUSIONS: In this malaria-endemic region of Tanzania, alpha (+)-thalassemia is common and clearly...

  14. α-地中海贫血基因型和红细胞参数关系的研究%Study on correlation between erythrocyte indices and genotype in cases with alpha-thalassemia

    Institute of Scientific and Technical Information of China (English)

    张永良; 汪伟山; 周玉球; 肖奇志; 谢建红

    2012-01-01

    Objective To investigate the correlation between the erythrocyte indices and the genotypes of alpha thalassemia.Methods 337 carriers with various genotypes of alpha-thalassaemia ( iron deficiency,alpha-thalassemia double heterozygote and homozygote,α-compounding β-thalassemia and abnormal hemoglobinopathy were excluded) were classified into three groups based on different genotypes of alpha-thalassaemia including silent thalassemia group (ST,83 cases),α-thalassemia trait group (TT,210cases) and intermediate thalassemia group( IT,44 cases),and 154 healthy adults were randomly choosed as normal control The erythrocyte indices involving in RBC,Hb,MCV,MCH,MCHC and RDW-CV were retrospectively analyzed and the difference of which was compared by analysis of variance and SNK test among aboved-mentioned groups.Results There were statistical significance among groups about erythrocyte indices except Hb F.The order of the level of MCV and MCH was NC [( 86.6 ± 5.2) fl,( 29.5 ± 2.1 ) pg] >ST[(80.1 ±3.3) fl,(26.7±1.3) pg] >TT[(68.5 ±3.4) fl,(22.0 ±1.2) pg] >IT[(66.6±7.1)fl,(20.0 ±2.2) pg,F =580.67,761.19,P <0.05].And the size of RDW-CV was IT(22.3 ±3.4)% >TT (14.9±1.2) % >ST(13.8±1.6)% >NC(13.2±1.4)%(F=347.25,P<0.05).In ST group,the value of MCHC of -α3.7/αα subgroup( 335.6 ± 8.0) g/L was higher than that of -α4.2/αα subgroup( 330 ±7.2) g/L and αTα/αα subgroup (328.4 ±9.5) g/L(F=6.07,P <0.05).Meanwhile,in IT group,the value of MCV of αTα/--SEA subgroup( 70.1 ± 7.2 ) fl was higher than that of -α3.7/--SEA subgroup ( 63.4 ±5.9) fl and -α4.2/--SEA subgroup ( 64.1 ± 4.0 ) fl ( F =5.55,P < 0.05 ).However,the value of MCHC of αTα/--SEA subgroup( 289.7 ± 21.2 ) g/L was lower than that of other two subgroups [( 306.3 ± 8.4 ),(306.1 ± 8.7) g/L,F =8.72,P <0.05].Except Hb A2 and Hb F,there was positive correlation between the number of deleted α-globin gene and that of RBC and RDW-CV ( r =0.318 and 0.580,P <0

  15. Biochemical studies of mouse brain tubulin: colchicine binding (DEAE-cellulose filter) assay and subunits (. cap alpha. and. beta. ) biosynthesis and degradation (in newborn brain)

    Energy Technology Data Exchange (ETDEWEB)

    Tse, Cek-Fyne

    1978-01-01

    A DEAE-cellulose filter assay, measuring (/sup 3/H)colchicine bound to colchicine binding protein (CBP) absorbed on filter discs, has been modified to include lM sucrose in the incubation medium for complexing colchicine to CBP in samples before applying the samples to filter discs (single point assay). Due to the much greater stability of colchicine binding capacity in the presence of lM sucrose, multiple time-point assays and least squares linear regression analysis were not necessary for accurate determination of CBP in hybrid mouse brain at different stages of development. The highest concentrations of CBP were observed in the 160,000g supernatant and pellet of newborn brain homogenate. Further studies of the modified filter assay documented that the assay has an overall counting efficiency of 27.3%, that DEAE-cellulose filters bind and retain all tubulin in the assay samples, and that one molecule of colchicine binds approximately one molecule of tubulin dimer. Therefore, millimoles of colchicine bound per milligram total protein can be used to calculate tubulin content. With this technique tubulin content of brain supernatant was found to be 11.9% for newborn, and 7.15% for 11 month old mice. Quantitative densitometry was also used to measure mouse brain supernatant actin content for these two stages. In vivo synthesis and degradation rates of tubulin ..cap alpha.. and ..beta.. subunits of two day mouse brain 100,000g supernatant were studied after intracerebral injection of (/sup 3/H)leucine. Quantitative changes of the ratio of tritium specific activities of tubulin ..cap alpha.. and ..beta.. subunits with time were determined. The pattern of change was biphasic. During the first phase the ratio decreased; during the second phase the ratio increased continuously. An interpretation consistent with all the data in this study is that the ..cap alpha.. subunit is synthesized at a more rapid rate than the ..beta.. subunit. (ERB)

  16. Presynaptic. cap alpha. -adrenoceptors and opiate receptors: inhibition of (/sup 3/H)noradrenaline release from rat cerebral cortex slices by different mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Schoffelmeer, A.N.M.; Mulder, A.H. (Vrije Univ., Amsterdam (Netherlands))

    1982-04-23

    The inhibitory effects of morphine and Cd/sup 2 +/ on electrically evoked (/sup 3/H)noradrenaline release from superfused brain slices were unaffected when release was enhanced by increasing the pulse duration, while the inhibitory effect of noradrenaline and the enhancing effect of phentolamine were diminished. A similar enhancement of (/sup 3/H)noradrenaline release by 4-aminopyridine reduced the modulatory effects of all drugs examined. Therefore there seem to be different mechanisms for the effect of presynaptic ..cap alpha..-adrenoceptors and opiate receptors on the availability of Ca/sup 2 +/ for the stimulus-secretion coupling process in noradrenergic nerve terminals.

  17. Cross sections for the /sup 14/N(n,p/sub 0/), (n,. cap alpha. /sub 0/), and (n,. cap alpha. /sub 1/) reactions from 0. 5 to 15 MeV. [0. 5 to 15 MeV, tables, diagrams

    Energy Technology Data Exchange (ETDEWEB)

    Morgan, G.L.

    1978-11-01

    Cross sections were measured for the /sup 14/N(n,p/sub 0/) reaction from 0.5 to 7.0 MeV and for the (n,..cap alpha../sub 0/) and (n,..cap alpha../sub 1/) reactions from 1 to 15 MeV and 4 to 15 MeV, respectively. The data were obtained using a gaseous scintillator containing N/sub 2/ and Xe mixtures. A linac was used as a pulsed, white neutron source with a 29-m flight path. The results of the measurement are compared to the current evaluated file for nitrogen; agreement is good for neutron energies below 8 MeV, but the measurement is substantially higher than the evaluation for neutron energies near 10 MeV. 28 references.

  18. The molecular basis of beta-thalassemia intermedia in southern China: genotypic heterogeneity and phenotypic diversity

    Directory of Open Access Journals (Sweden)

    Sun Manna

    2010-02-01

    Full Text Available Abstract Background The clinical syndrome of thalassemia intermedia (TI results from the β-globin genotypes in combination with factors to produce fetal haemoglobin (HbF and/or co-inheritance of α-thalassemia. However, very little is currently known of the molecular basis of Chinese TI patients. Methods We systematically analyzed and characterized β-globin genotypes, α-thalassemia determinants, and known primary genetic modifiers linked to the production of HbF and the aggravation of α/β imbalance in 117 Chinese TI patients. Genotype-phenotype correlations were analyzed based on retrospective clinical observations. Results A total of 117 TI patients were divided into two major groups, namely heterozygous β-thalassemia (n = 20 in which 14 were characterized as having a mild TI with the Hb levels of 68-95 g/L except for five co-inherited αααanti-3.7 triplication and one carried a dominant mutation; and β-thalassemia homozygotes or compound heterozygotes for β-thalassemia and other β-globin defects in which the β+-thalassemia mutation was the most common (49/97, hemoglobin E (HbE variants was second (27/97, and deletional hereditary persistence of fetal hemoglobin (HPFH or δβ-thalassemia was third (11/97. Two novel mutations, Term CD+32(A→C and Cap+39(C→T, have been detected. Conclusions Chinese TI patients showed considerable heterogeneity, both phenotypically and genotypically. The clinical outcomes of our TI patients were mostly explained by the genotypes linked to the β- and α-globin gene cluster. However, for a group of 14 patients (13 β0/βN and 1 β+/βN with known heterozygous mutations of β-thalassemia and three with homozygous β-thalassemia (β0/β0, the existence of other causative genetic determinants is remaining to be molecularly defined.

  19. /sup 45/Ca efflux for myometrial cells: comparison of the effects of prostaglandin F/sub 2/. cap alpha. (PGF/sub 2/), oxytocin (OT) and arachidonate (A)

    Energy Technology Data Exchange (ETDEWEB)

    Katona, G.; Molnar, M.; Toth, M.; Hertelendy, F.

    1986-03-01

    The aim of this study was to measure PGF/sub 2..cap alpha../-induced Ca/sup 2 +/ release from uterine cells and to compare this to the actions of OT and A. Smooth muscle cells isolated from the uterus (shell gland) of laying hens were cultured for 7 days in M199 plus 10% fetal calf serum. The cells were treated with digitonin (20..mu..M) and preloaded with /sup 45/Ca for 40 min. Addition of PGF/sub 2..cap alpha../ caused a biphasic /sup 45/Ca-efflux. There was a small but significant /sup 45/Ca-release within 30 sec (rapid phase) followed by a larger one within 7 min (slow phase). In comparison, both OT and A stimulated /sup 45/Ca efflux during a single, slow phase. The maximal effect of A was observed at < 7 min, whereas that of OT was slower, peaking after 7 min. Mepacrin, an inhibitor of A release, attenuated the action of OT without having any effect on A promoted /sup 45/Ca-efflux. Indomethacin, an inhibitor of PG synthase, failed to suppress the Ca-releasing effect of A suggesting the A itself or a lipoxygenase product may have been responsible for the observed effects. Moreover, these results provide suggestive evidence that A release is an important step in the action of various uterotonic agents converging on the mobilization of intracellular Ca.

  20. Low Bone Mass in Thalassemia

    Science.gov (United States)

    4 Low Bone Mass in Thalassemia • In addition to a diet rich in calcium and vitamin D, your doctor may recommend taking calcium and/or vitamin D ... Zoledronic acid may be beneficial to patients with thalassemia and osteoporosis; other trials are investigating whether increasing ...

  1. 胎血MCV、MCH检测在o地中海贫血诊断中的价值%Analysis of fetal blood MCV and MCH in prenatal diagnosis of alpha thalassemia

    Institute of Scientific and Technical Information of China (English)

    胡雪华; 李东明

    2011-01-01

    Objective: To investigate the characteristics and reference range of mean corpuscular volume ( MCV) in prenatal umbilical cord blood, mean corpuscular hemoglobin ( MCH) , and the value were compared between MCV and MCH in the diagnosis of thalassemia (thai). Methods: Cordocentesis were implemented 1 563 cases gravidas, and umbilical cord blood were used to detect the blood cells and thai gene. Results; MCV and MCH of cord blood were (106.9±10.9) fl, (121.7 ±8.5) fland (33.4+4.7) pg, (41. 3 ±2. 8) pg in group of thai and normal respectively. The reference range of MCV and MCH was ( 105 ~ 138. 4) fl and (35. 8 ~ 46. 8) pg in prenatal umbilical cord blood. The sensitivity, specificity, accuracy, positive and negative predictive of MCH in screening for alpha thai were higher than those of MCV, and The sensitivity of MCH screening for osculant and major alpha thai were 100% . Conclusion; MCV, MCH of prenatal umbilical cord blood was significantly higher than those of neonatal and adult. It is necessary to establish the reference range of MCV and MCH of umbilical cord blood. To provide a basis for the diagnosis of alpha thala, MCH and MCH should be detected by using umbilical cord blood.%目的 探讨产前脐血MCV、MCH特点及参考范围,比较MCV、MCH诊断α地中海贫血(地贫)的价值.方法 对1563例孕妇经腹行脐带穿刺术,取脐血进行血细胞和地贫基因分析,比较MCV、MCH筛查α地贫的灵敏度和特异性等指标.结果 α地贫组、正常组脐血MCV和MCH分别为(106.9+10.9)fl、(121.7±8.5)fl和(33.4±4.7)pg、(41.3±2.8)Pg,产前脐血MCV和MCH的参考范围为(105.0~138.4)fl和(35.8 ~46.8)pg.MCH筛查α地贫的灵敏度、特异度、准确度、阳性预测值和阴性预测值均高于MCV,其筛查中间型、重型α地贫灵敏度为100%.结论 产前脐血MCV、MCH的参考范围明显高于新生儿及成人,有必要建立参考范围;产前脐血MCV、MCH检测可为α地贫临床诊断提供依据,MCH筛查α地贫优于MCV.

  2. Thalassemias and hemoglobinopathies in Turkey.

    Science.gov (United States)

    Canatan, Duran

    2014-01-01

    Thalassemias and hemoglobinopathies are a serious health problem in Turkey. There is a 70-year history of thalassemia in Turkey. The first patient with β-thalassemia major (β-TM) was reported in 1941. The first clinical and hematological studies were published by Aksoy in 1958. The overall incidence of β-thalassemia (β-thal) was reported by Çavdar and Arcasoy to be 2.1% in 1971. Important steps such as written regulations, education and prevention campaigns, have been taken to prevent thalassemia in Turkey by the Ministry of Health (MOH), the Turkish National Hemoglobinopathy Council (TNHC) and the Thalassemia Federation of Turkey (TFT) since 2000. A national hemoglobinopathy prevention program was started in provinces with a high prevalence by the MOH in 2003. While the percentage of premarital screening test was 30.0% of all couples in 2003, it reached 86.0% in 2013. While the number of newborn with thalassemias and hemoglobinopathies was 272 in 2002, it had dropped to 25 in 2010. There has been a 90.0% reduction of affected births in the last 10 years.

  3. Non-transfusion-dependent thalassemias.

    Science.gov (United States)

    Musallam, Khaled M; Rivella, Stefano; Vichinsky, Elliott; Rachmilewitz, Eliezer A

    2013-06-01

    Non-transfusion-dependent thalassemias include a variety of phenotypes that, unlike patients with beta (β)-thalassemia major, do not require regular transfusion therapy for survival. The most commonly investigated forms are β-thalassemia intermedia, hemoglobin E/β-thalassemia, and α-thalassemia intermedia (hemoglobin H disease). However, transfusion-independence in such patients is not without side effects. Ineffective erythropoiesis and peripheral hemolysis, the hallmarks of disease process, lead to a variety of subsequent pathophysiologies including iron overload and hypercoagulability that ultimately lead to a number of serious clinical morbidities. Thus, prompt and accurate diagnosis of non-transfusion-dependent thalassemia is essential to ensure early intervention. Although several management options are currently available, the need to develop more novel therapeutics is justified by recent advances in our understanding of the mechanisms of disease. Such efforts require wide international collaboration, especially since non-transfusion-dependent thalassemias are no longer bound to low- and middle-income countries but have spread to large multiethnic cities in Europe and the Americas due to continued migration.

  4. Effect of. cap alpha. -,. beta. -adrenergic receptor agonists and antagonists of the efflux of /sup 22/Na and uptake of /sup 42/K by rat brain cortical slices

    Energy Technology Data Exchange (ETDEWEB)

    Phillis, J.W.; Wu, P.H.; Thierry, D.L.

    1982-03-18

    The effects of norepinephrine on ion fluxes in rat brain cortical slices have now been ascertained. /sup 22/Na efflux and /sup 42/K influx are enhanced by norepinephrine. The increase in ion fluxes can be blocked by ouabain, phentolamine and propranolol, suggesting that the catecholamine activates a membrane sodium pump by a receptor-mediated step. The facilitation of /sup 22/Na efflux is stereospecific as demonstrated by the very weak action of D-norepinephrine at 10/sup -5/ M concentration. Various ..cap alpha..-adrenergic and ..beta..-adrenergic receptor agonists, including oxymetazoline, naphazoline, clonidine, tramazoline, methoxamine, phenylephrine, L-isoproterenol and methoxyphenamine are potent stimulants of the sodium pump as demonstrated by their enhancement of ion fluxes in rat brain cortical slices. The results are consistent with the hypothesis that norepinephrine hyperpolarizes central neurons by activating an ouabain-sensitive, receptor-mediated sodium pump.

  5. Deuteriation exchange (with the deuteriated catalyst surface) and the ratio of dehydrogenation and dehydration of. cap alpha. - and. beta. -substituted ethanols on basic oxides

    Energy Technology Data Exchange (ETDEWEB)

    Thomke, K.

    1977-01-01

    The pulsed reactions of ethanol, 1- and 2-propanol, 1- and 2-butanol, 2-methyl-2-propanol, and 3-pentanol on deuteriated magnesium, samarium, thorium, and lanthanum oxides showed that no deuterium was incorporated at a carbon of 2-methyl-2-propanol (i.e., that the reaction did not proceed by the E1cB mechanism); that all the secondary alcohols formed olefins and ketones and incorporated deuterium only in the ..beta..-position; and that primary alcohols formed olefins and aldehydes on all catalysts except lanthanum oxide (which catalyzed only dehydration of primary alcohols) and incorporated deuterium in the ..cap alpha..-position on magnesium and thorium oxide. The mechanism is discussed. Table.

  6. [Osteodystrophy in thalassemia major].

    Science.gov (United States)

    Bisbocci, D; Livorno, P; Modina, P; Gambino, M; Damiano, P; Cantoni, R; Villata, E; Chiandussi, L

    1993-01-01

    Subjects with thalassemia major frequently have bone disorders of debatable pathogenesis. We attempt here to analyze the relationships between siderosis and thalassemic osteodystrophy by assessing calcium-phosphorus balance, hormone-vitamin homeostasis, osteoblastic-osteoclastic activity parameters, and bone mineral density (BMD) in 30 patients with thalassemia major (16 males, 14 females, age range 17-30 years). We found a significant increase in ferritin (p < 0.001) and significant decreases in serum i-PTH, 25OHD3, 1.25(OH)2D3, osteocalcin, estradiol, testosterone and FT4 (p < 0.001) in both sexes. In all patients a net decrease of bone mineral density was documented (p < 0.001). These results were then submitted to linear regression analysis: positive correlations between BMD and FT3, testosterone, estradiol (p < 0.01), were documented, and an inverse correlation between osteocalcin and ferritin was confirmed. Our findings suggest that thalassemic osteodystrophy is the result of several inhibitory influences on osteoblastic activity and bone apposition (related to hormone deficits and siderosis) which are aggravated further by anemia, chronic hypoxia and red marrow expansion.

  7. The co-inheritance of alpha-thalassemia and sickle cell anemia is associated with better hematological indices and lower consultations rate in Cameroonian patients and could improve their survival.

    Directory of Open Access Journals (Sweden)

    Maryam Bibi Rumaney

    Full Text Available BACKGROUND: Co-inheritance of α-thalassemia was reported to be associated with a delayed age of disease onset among Cameroonian Sickle Cell Anemia (SCA patients. The present study aimed to explore the correlation between α-thalassemia, hematological indices, and clinical events in these patients. METHODS AND FINDINGS: We studied 161 Cameroonian SCA patients and 103 controls (59.1% HbAA with median ages of 17.5 and 23 years. RFLP-PCR was used to confirm SCA genotype and to describe haplotypes in the HBB-like genes cluster. Multiplex Gap-PCR was performed to investigate the 3.7 kb α-globin gene deletions. SNaPshot PCR, capillary electrophoresis and cycle sequencing were used for the genotyping of 10 SNPs in BCL11A, HMIP1/2, OR51B5/6 and HBG loci, known to influence HbF levels. Generalised linear regression models adjusted for age, sex and SNPs genotypes was used to investigate effects of α-thalassemia on clinical and hematological indices. The median rate of vaso-occlusive painful crisis and hospitalisations was two and one per year, respectively. Stroke was reported in eight cases (7.4%. Benin haplotype was the most prevalent (66.3%; n = 208 chromosomes. Among patients, 37.3% (n = 60 had at least one 3.7 kb deletion, compared to 10.9% (n = 6 among HbAA controls (p<0.001. Among patients, the median RBC count increased with the number of 3.7 kb deletions [2.6, 3.0 and 3.4 million/dl, with no, one and two deletions (p = 0.01]. The median MCV decreased with the number of 3.7 kb deletion [86, 80, and 68fl, with no, one and two deletions (p<0.0001], as well as median WBC counts [13.2, 10.5 and 9.8×109/L (p<0.0001. The co-inheritance of α-thalassemia was associated with lower consultations rate (p = 0.038. CONCLUSION: The co-inheritance of α-thalassemia and SCA is associated with improved hematological indices, and lower consultations rate in this group of patients. This could possibly improve their survival and explain the

  8. Microcytic hypochromic anemia patients with thalassemia : Genotyping approach

    Directory of Open Access Journals (Sweden)

    Rahim Fakher

    2009-03-01

    Full Text Available Background: Microcytic hypochromic anemia is a common condition in clinical practice, and alpha-thalassemia has to be considered as a differential diagnosis. Aims: This study was conducted to evaluate the frequency of α-gene, β-gene and hemoglobin variant numbers in subjects with microcytic hypochromic anemia. Setting And Designs: Population-based case-control study in the Iranian population. Materials And Methods: A total of 340 subjects from southwest part of Iran were studied in the Research Center of Thalassemia and Hemoglobinopathies (RCTH, Iran. Genotyping for known a- and b-gene mutations was done with gap-PCR and ARMS. In cases of some rare mutations, the genotyping was done with the help of other techniques such as RFLP and ARMS-PCR. Statistical Analysis: Statistical analysis was carried out by SPSS 11.5 and an independent-sample t test. Results: Out of the total 340 individuals, 325 individuals were evaluated to have microcytic hypochromic anemia based on initial hematological parameters such as MCV< 80 fl; MCH < 27 pg; the remaining 15 patients were diagnosed with no definite etiology. The overall frequency of -α3.7 deletion in 325 individuals was 20.3%. The most frequent mutations were IVS II-I, CD 36/37 and IVS I-110 with frequencies of 6.31%, 5.27% and 1.64%, respectively. Only, there was a significant difference between beta-thalassemia trait and beta-thalassemia major with regard to MCV (P < 0.05 and MCH (P < 0.05 indices, and also MCH index between beta-thalassemia trait and Hb variants (P < 0.05. Conclusion: Molecular genotyping provides a rapid and reliable method for identification of common, rare and unknown a- and b-gene mutations, which help to diagnose unexplained microcytosis and thus prevent unnecessary iron supplementation.

  9. Approaches to management of beta-thalassemia intermedia

    Directory of Open Access Journals (Sweden)

    Joseph E. Maakaron

    2013-03-01

    Full Text Available Thalassemia intermedia is a genetically diverse group of diseases that is the result of an imbalance in the production of the alpha and beta chains with ensuing chronic hemolysis, ineffective erythropoiesis, and iron overload.Resulting complications include bone changes, hypercoagulability, and end-organ damage due to iron overload. This decade has witnessed major breakthroughs in the management of thalassemia. In this article, we examine these novelties in therapy including iron chelation therapy, stem cell transplant, and gene therapy.Iron chelation therapy has been revolutionized with the advent of deferasirox, a once-daily oral iron chelator, that has been shown to be safe and efficacious.Gene therapy was also at the core of this revolution with the discovery of novel gene elements and viral vectors allowing for better control and improved outcomes.

  10. A molecular epidemiologic study of thalassemia using newborns' cord blood in a multiracial Asian population in Singapore: results and recommendations for a population screening program.

    Science.gov (United States)

    Kham, S K; Yin, Shirley Kham Kow; Quah, Thuan Chong; Loong, Ai Mei; Tan, Poh Lin; Fraser, Angus; Chong, S S; Chuan, Samuel Chong Siong; Yeoh, A E; Eng-Juh, Allen Yeoh

    2004-12-01

    DNA technology provides a new avenue to perform neonatal screening tests for single-gene diseases in populations of high frequency. Thalassemia is one of the high-frequency single-gene disorders affecting Singapore and many countries in the malaria belt. The authors explored the feasibility of using PCR-based diagnostic screening on 1,116 unselected sequential cord blood samples for neonatal screening. The cord blood samples were screened for the most common reported alpha- and beta-thalassemia mutations in each ethnic group (Chinese, Malays, and Indians) in a multiracial population. The carrier frequency for alpha-thalassemia mutations was about 6.4% in the Chinese (alpha deletions = 3.9%, alpha deletions = 2.5%), 4.8% in Malays, and 5.2% in Indians. Only alpha deletions were observed in the Chinese. The carrier frequency for beta-thalassemia mutations was 2.7% in the Chinese, 6.3% in Malays, and 0.7% in Indians. Extrapolating to the population distribution of Singapore, the authors found a higher overall expected carrier frequency for alpha- and beta-thalassemia mutations of 9% compared with a previous population study of 6% by phenotype. The highly accurate results make this molecular epidemiologic screening an ideal method to screen for and prevent severe thalassemia in high-risk populations.

  11. Assessing Parental Knowledge About Thalassemia in a Thalassemia Center of Karachi, Pakistan.

    Science.gov (United States)

    Maheen, Humaira; Malik, Farrukh; Siddique, Barera; Qidwai, Asim

    2015-12-01

    Thalassemia is the leading haemoglobinopathy after sickle cell anemia that accounts for 1.5 % of the global population. In Pakistan, every 1-4 per 1000 infants suffers from Thalassemia. Regardless of being a population "at high risk" for Thalassemia major, evidence suggest that Pakistanis possess poor knowledge of the disease. The present study aimed to assess parents' accurate knowledge about Thalassemia disease at Afzaal Memorial Thalassemia Foundation in Karachi, Pakistan. A total of 172 parents of existing patients who were receiving regular blood transfusion from the center were included in the study. Parents' knowledge was assessed via a pre-tested and validated Thalassemia knowledge questionnaire. Findings show that 40 % of the sample showed lower knowledge scores about Thalassemia. Among different ethnic origins, Urdu speaking respondents showed a higher average score of correct knowledge about Thalassemia major (21.6 ± 4.41) as compared to the Siraiki (17.9 ± 4.48) and the Pathans (17.2 ± 4.34). These latter two ethnic groups also showed poor knowledge about Thalassemia minor. Generally parents provided correct answers about treatment of Thalassemia major. The findings suggest targeted interventions are required for high risk ethnic groups. Thalassemia education programs should be offered to extended family members of existing patients by all Thalassemia centers. High risk ethnic groups (Siraiki and Pathan) need rigorous interventions, and Thalassemia worker program should be introduced nationwide.

  12. Synthesis of biological markers in fossil fuels. 4. C/sub 27/, C/sub 28/, and C/sub 29/ 13. beta. ,17. cap alpha. (H)-diasteranes

    Energy Technology Data Exchange (ETDEWEB)

    Bauer, P.E.; Nelson, D.A.; Watt, D.S.; Reibenspies, J.H.; Anderson, O.P.; Seifert, W.K.; Moldowan, J.M.

    1985-12-27

    The rearrangement of 5-cholestene to (20epsilon)-13(17)-diacholestenes, separation of C-20 epimers, and further reduction provided an unambiguous synthesis of the biomarkers (20R)- and (20S)-13..beta..,17..cap alpha..(H)-diacholestanes. Repetition of this sequence using (24R)-5-campestene or (24R)-5-stigmastene provided the analogous C/sub 28/ and C/sub 29/ diasteranes. 15 references, 1 figure.

  13. Hemoglobin profiles of siblings of thalassemia patients

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    Muhammad Riza

    2015-03-01

    Full Text Available Background Thalassemia and hemoglobinopathies are the most common inherited disorders in many areas of the world, including South East Asia. The siblings of thalassemia major is a group of high risk to carry the gene of thalassemia. Determining the carrier is useful for early treatment planning and prevention to the next child. Objective To determine carrier status among siblings of thalassemia patients using a capillary electrophoresis system. Methods A cross-sectional study on the siblings of thalassemia major patients was performed from January 2011 to February 2012 at Dr. Moewardi Hospital. Complete blood counts were performed in the siblings. Subjects with mean corpuscular volume (MCV <80 fl and mean corpuscular hemoglobin (MCH <27 pg were subjected to analize hemoglobin fraction by capillary electrophoresis. Results Of the 26 subjects, there were 12 males and 14 females. The mean age was 9.38 (SD 6.8 years (range 1 to 29 years. From the siblings, 10 were identified as normal, 5 were identified as ß thalassemia carriers and 5 were hemoglobin E (HbE carriers. Six siblings were diagnosed with ß thalassemia/ HbE. Conclusion There are high occurrence of the two common types of thalassemia carriers (ß and HbE in our small group of subjects who had a family history of thalassemia. Most of the siblings of thalassemia had low MCV and MCH. [Paediatr Indones. 2015;55:70-3.].

  14. 一个伴α地中海贫血X连锁智力低下综合征家系的基因突变研究%Mutation analysis for a Chinese family featuring X-linked alpha thalassemia/mental retardation syndrome

    Institute of Scientific and Technical Information of China (English)

    林少宾; 孙宏钰; 宋新明; 陈路明; 杜敏联; 陈争

    2013-01-01

    目的 对1个X连锁智力低下伴α地中海贫血综合征(alpha thalassaemia/mental retardation syndrome,X-linked,ATR-X)的家系进行致病基因突变研究.方法 根据患者的临床表型和家系的遗传特点,应用X染色体短串联重复序列位点的连锁分析,定位智力低下的基因位点,初步锁定目的基因后,应用聚合酶链反应技术扩增致病基因外显子及剪切位点,应用DNA序列测定技术分析患者及其父母的致病性突变.地中海贫血基因检测确定患者基因型.结果 连锁分析提示ATRX基因可能是家系智力低下的致病基因.全部3例患者ATRX基因第9外显子均存在c.736C>T (p.R246C)突变.3例患者的母亲及祖母均为该突变携带者.其余8名家系成员均未检测到该基因突变.α地中海贫血检测证实先证者及另1例患者均携带α珠蛋白基因的缺失,基因型分别为-α3.7/αα和--sea/αα.结论 该家系ATRX基因的错义突变c.736C>T位于该基因突变热点区域,p.R246C可能影响ATRX蛋白锌指蛋白结构域的功能,可能是该家系ATR-X综合征的发病原因.%Objective To identify potential mutation in a Chinese family featuring X-linked alpha thalassemia/mental retardation syndrome (ATR-X).Methods Based on clinical symptoms and inheritance pattern,linkage analysis of X chromosome short tandem repeats (X-STR) loci was carried out to locate the candidate gene.Subsequently,sequences of exons and exon-intron boundaries of the candidate gene were amplified with polymerase chain reaction (PCR).Potential mutations were detected by direct DNA sequencing.All patients were also analyzed for the trait of thalassemia.Results Linkage analysis indicated the candidate gene to be ATRX.Subsequently,a homozygous missense mutation c.736C>T (p.R246C) was found in exon 9 of ATRX in all of the 3 patients.And a heterozygous mutation c.736C>T (p.R246C) was also identified in the patient's mother and grandmother.Similar mutations were not

  15. Renal tubular dysfunction with nephrocalcinosis in a patient with beta thalassemia minor

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    Prabahar Murugesan

    2008-01-01

    Full Text Available Thalassemia is a hereditary anemia resulting from defect in hemoglobin production. Beta thalassemia is due to impaired production of beta globin chains, leading to a relative excess of alpha globin chains. The term beta thalassemia minor is used to describe heterozygotes, who carry one normal beta globin allele and one beta thalassemic allele. The vast majority of these patients are asymptomatic. However, a variety of renal tubular abnormalities including hypercalciuria, hypo-magnesemia with renal magnesium wasting, decreased tubular absorption of phosphorus, hypo-uricemia with renal uric acid wasting, renal glycosuria and tubular proteinuria have been described even in patients with beta thalassemia minor. We here in report a 24-year old female patient who was found to have thalassemia minor and nephrocalcinosis with evidence of renal tubular dysfunction. Investigations revealed normal renal function, hypercalciuria, reduced tubular reabsorption of phos-phorus, hypomagnesemia and renal magnesium wasting. Screening for aminoaciduria was found to be negative. An acid loading test revealed normal urinary acidification. Ultrasonogram of the abdomen revealed nephrocalcinosis and splenomegaly. Detailed work up for anemia showed normal white cell and platelet count while peripheral smear showed microcytic hypochromic anemia with few target cells. Hemoglobin electrophoresis revealed hemoglobin A of 92%, hemoglobin A2 of 6.2% and hemo-globin F of 1.8% consistent with beta thalassemia minor. Her parental screening was normal. A diag-nosis of beta thalassemia minor with renal tubular dysfunction was made and the patient was started on thiazide diuretics to reduce hypercalciuria and advised regular follow-up.

  16. Thalassemia and Hemoglobin E in Southern Thai Blood Donors

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    Manit Nuinoon

    2014-01-01

    Full Text Available Thalassemia and hemoglobin E (Hb E are common in Thailand. Individuals with thalassemia trait usually have a normal hemoglobin concentration or mild anemia. Therefore, thalassemic individuals who have minimum acceptable Hb level may be accepted as blood donors. This study was aimed at determining the frequency of α-thalassemia 1 trait, β-thalassemia trait, and Hb E-related syndromes in Southern Thai blood donors. One hundred and sixteen voluntary blood donors, Southern Thailand origin, were recruited for thalassemia and Hb E screening by red blood cell indices/dichlorophenolindophenol precipitation test. β-Thalassemia and Hb E were then identified by high performance liquid chromatography and 4 common α-thalassemia deletions were characterized by a single tube-multiplex gap-polymerase chain reaction. Overall frequency of hemoglobinopathies was 12.9%, classified as follows: homozygous α-thalassemia 2 (1.7%, heterozygous α-thalassemia 1 (1.7%, heterozygous β-thalassemia without α-thalassemia (0.9%, heterozygous Hb E without α-thalassemia (5.2%, double heterozygotes for Hb E/α-thalassemia 1 (1.7%, homozygous Hb E without α-thalassemia (0.9%, and homozygous Hb E with heterozygous α-thalassemia 2 (0.9%. The usefulness of thalassemia screening is not only for receiving highly effective red blood cells in the recipients but also for encouraging the control and prevention program of thalassemia in blood donors.

  17. AB063. Prevalence of thalassemias and hemoglobinopathies detected via high performance liquid chromatography in Filipinos

    Science.gov (United States)

    Silao, Catherine Lynn; Fabella, Terence Diane; Yuson, Ernesto; Naranjo, Maria Liza; Padilla, Carmencita

    2015-01-01

    Background The thalassemias and hemoglobinopathies are groups of autosomal recessive inherited blood disorders affecting the quantity and quality of hemoglobin. Patients with the disease can vary from clinically asymptomatic to transfusion dependent individuals. It is considered prevalent in many parts of the world particularly in Southeast Asia. Thus, screening and prevalence determination of these diseases are important in the Filipino population. The study aims to determine the prevalence of thalassemias and hemoglobinopathies in the Philippines using high performance liquid chromatography. Methods Referred patients by hematologists from different parts of the country from October 2008 to December 2014 were included. Peripheral blood extracted from the subjects, were hemolyzed and screened for thalassemias and hemoglobinopathies using VariantTM HPLC. Data interpretations were based on levels of the HbA2 Fetal Hb and HbA detected. Results Majority of the patients were beta thalassemics followed by alpha-thalassemics. Hemoglobin E was found in 1% of the population tested while 2% of the patients have beta thalassemia with HbE interaction. Conclusions A significant proportion of thalassemias and hemoglobinopathies were determined from the 6-year screening of Filipinos using VariantTM HPLC. The results of this study provide not only confirmation of the occurrence and prevalence of these growing and diverse groups of genetic blood diseases but also suggest that the use of HPLC is a useful screening tool.

  18. Application value of OSCAR syetem in prenatal screen of chromosome disease and severeα-thalassemia

    Institute of Scientific and Technical Information of China (English)

    Yi Ling; Song Jin; Chun-Xia Hu; Rui-XiANan; Fu Huo; Ning Zhang; Tu-Zhao Xie; Qun-Hua Shi

    2016-01-01

    Objective:To study the value of combining serum and ultrasound nuchal translucency thickness (NT) measurement for One-stop Clinic of Risk Assessment (OSCAR) in Hainan Province in prenatal diagnose of chromosomal disorders and thalassemia diagnosis.Methods:The patients of 11-13+ 6 weeks in our hospital for regularly standardized checking were selected for OSCAR prenatal screening, the patients of the Down's and severe thalassemia at high risk were selected for prenatal diagnosis of fetal karyotype and thalassemia gene checking, then pregnancy outcomes was followed up. Rate of OSCAR in fetal chromosomal disease and the diagnostic value in fetal thalassemia was detected.Results:The positive rate of OSCAR Down's screening was 9.8%, the detection rate was 90%. The incidence of chromosomal abnormalities and severe alpha thalassemia were increased as NT thickening and tricuspid or venous ductus regurgitation.Conclusions: OSCAR Down's screening system for early pregnancy is noninvasive, affordable and it is preferred prenatal screening through comprehensive evaluation.

  19. Failure to replicate the internal structure of Greek-specific thalassemia quality of life instrument in adult thalassemia patients in Sabah

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    Keowmani T

    2016-02-01

    Full Text Available Thamron Keowmani,1 Lily Wong Lee Lee21Clinical Research Centre, 2Hematology Unit, Queen Elizabeth Hospital, Kota Kinabalu, Sabah, MalaysiaPurpose: To study the validity and reliability of the Malay version of the Specific Thalassemia Quality of Life Instrument (STQOLI in Sabah’s adult thalassemia patients.Patients and methods: This cross-sectional study was done at Thalassemia Treatment Centre, Queen Elizabeth Hospital in Sabah, Malaysia. Eighty-two adult thalassemia patients who fulfilled the inclusion and exclusion criteria were conveniently selected for participation in the study. The English version of STQOLI was translated into Malay by using forward and back translations. The content of the questionnaire was validated by the chief hematologist of the hospital. The construct validity of the 40-item questionnaire was assessed by principal component analysis with varimax rotation and the scale reliability was assessed by Cronbach’s alpha.Results: The study failed to replicate the internal structure of the Greek STQOLI. Instead, 12 factors have been identified from the exploratory factor analysis, which accounted for 72.2% of the variance. However, only eight factors were interpretable. The factors were iron chelation pump impact, transfusion impact, time spent on treatment and its impact on work and social life, sex life, side effects of treatment, cardiovascular problems, psychology, and iron chelation pill impact. The overall scale reliability was 0.913.Conclusion: This study was unable to replicate the internal structure of the Greek STQOLI in Sabah’s adult thalassemia patients. Instead, a new structure has emerged that can be used as a guide to develop a questionnaire specific for adult thalassemia patients in Sabah. Future research should focus on the eight factors identified from this study.Keywords: STQOLI, validity, reliability, Malay, transfusion

  20. Alpha-catenin-Dependent Recruitment of the Centrosomal Protein CAP350 to Adherens Junctions Allows Epithelial Cells to Acquire a Columnar Shape

    Science.gov (United States)

    Zurbano, Angel; Formstecher, Etienne; Martinez-Morales, Juan R.; Bornens, Michel; Rios, Rosa M.

    2015-01-01

    Epithelial morphogenesis involves a dramatic reorganisation of the microtubule cytoskeleton. How this complex process is controlled at the molecular level is still largely unknown. Here, we report that the centrosomal microtubule (MT)-binding protein CAP350 localises at adherens junctions in epithelial cells. By two-hybrid screening, we identified a direct interaction of CAP350 with the adhesion protein α-catenin that was further confirmed by co-immunoprecipitation experiments. Block of epithelial cadherin (E-cadherin)-mediated cell-cell adhesion or α-catenin depletion prevented CAP350 localisation at cell-cell junctions. Knocking down junction-located CAP350 inhibited the establishment of an apico-basal array of microtubules and impaired the acquisition of columnar shape in Madin-Darby canine kidney II (MDCKII) cells grown as polarised epithelia. Furthermore, MDCKII cystogenesis was also defective in junctional CAP350-depleted cells. CAP350-depleted MDCKII cysts were smaller and contained either multiple lumens or no lumen. Membrane polarity was not affected, but cortical microtubule bundles did not properly form. Our results indicate that CAP350 may act as an adaptor between adherens junctions and microtubules, thus regulating epithelial differentiation and contributing to the definition of cell architecture. We also uncover a central role of α-catenin in global cytoskeleton remodelling, in which it acts not only on actin but also on MT reorganisation during epithelial morphogenesis. PMID:25764135

  1. Genotype of 168 child cases with high-risk thalassemia%168例高危地中海贫血儿童基因谱分析

    Institute of Scientific and Technical Information of China (English)

    刘宁毅

    2013-01-01

    Objective To analyze the genotypes of high-risk thalassemia (thalassemia) children.Methods Samples were collected from 168 children with high-risk thalassemia and the genotypes of α-thalassemia and β-thalassemia were detected.The α-thalassemia cases were detected for three alpha deletion genotypes (-SEA/-a 3.7/-a 4.2) and three non-deletion mutant α-thalassemia (HbCS HbQS HbWS).The alpha deletion genotype was detected with single-tube multiplex PCR technology,non-deletion mutant α-thalassemia and β-thalassemia (17 sites) in common Chinese people were detected with by using reverse dot blot hybridization.Results Totally 49 o-thalassemia cases were detected from 168 children at high risk of thalassemia,accounted for 29.17% ;including 39 deletion α-thalassemia cases,accounting for 79.59% of the alpha-thalassemia cases,10 non-deletion mutant a-thalassemia cases,accounting for 20.41% of α-thalassemia.Twenty-seven deletion β-thalassemia cases were detected accounting for 16.07%; including double heterozygotes in 5 cases,accounting for 2.98% ; detection composite α β-groundpoor in 12 cases,accounting for 7.14%; the total detection rate was 55.36%.Conclusions The incidence of thalassemia in Qinzhou is high,and large-scale screening of thalassemia among population of child-bearing age is indicated for improvement of prenatal care and reduce the incidence of thalassemia ion Qinzhou.%目的 应用基因诊断技术探讨高危地中海贫血(地贫)儿童的常见基因谱的分布特征. 方法 用钦州地区168例高危地贫的儿童样本分别检测α-地贫及β-地贫基因型,而α-地贫分为3种d缺失型基因检测(-SEA/,-α 3.7/-α4.2)和3种非缺失突变型仅地贫(HbCS,HbQS,HbWS).α缺失型基因检测应用单管多重PCR技术进行检测,非缺失突变型α地贫和β-地贫(检测中国人常见的17种位点)均采用反向斑点杂交法. 结果 在168例进行地贫基因检查的钦州地区高危地

  2. AWARENESS ABOUT THALASSEMIA: A SURVEY REPORT

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    Safila Naveed

    2014-02-01

    Full Text Available To determine the awareness among student of Pharm D, MBBS and general population with thalassemia major (TM regarding the disease. Methods: This (cross sectional study was conducted among students of MBBS, Pharm. D in different private and government sector universities in Karachi having close ended questions related to their knowledge about thalassemia from Sep 2013 to October 2013. Different Parents were interviewed using a pre designed questionnaire. Questions regarding duration of illness, screening of blood awareness regarding, mode of transmission of disease, prevention and treatment were asked. Results: We’ve determined the awareness ratio and found out that the awareness rate of thalassemia was not up to the mark as we thought. Among 200 populations only 22% of the people had good knowledge about thalassemia and rest 78% of people were not well aware of the disease as well as its consequences. Conclusion: From this survey we conclude that the awareness of people on thalassemia is negligible.

  3. AWARENESS ABOUT THALASSEMIA: A SURVEY REPORT

    Directory of Open Access Journals (Sweden)

    Safila Naveed

    2014-02-01

    Full Text Available Objective: To determine the awareness among student of Pharm D, MBBS and general population with thalassemia major (TM regarding the disease. Methods: This (cross sectional study was conducted among students of MBBS, Pharm. D in different private and government sector universities in Karachi having close ended questions related to their knowledge about thalassemia from Sep 2013 to October 2013. Different Parents were interviewed using a pre designed questionnaire. Questions regarding duration of illness, screening of blood awareness regarding, mode of transmission of disease, prevention and treatment were asked. Results: We’ve determined the awareness ratio and found out that the awareness rate of thalassemia was not up to the mark as we thought. Among 200 populations only 22% of the people had good knowledge about thalassemia and rest 78% of people were not well aware of the disease as well as its consequences. Conclusion: From this survey we conclude that the awareness of people on thalassemia is negligible.

  4. Recent advances in gene therapy for thalassemia

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    J V Raja

    2012-01-01

    Full Text Available Thalassemias are genetically transmitted disorders. Depending upon whether the genetic defects or deletion lies in transmission of α or β globin chain gene, thalassemias are classified into α and β-thalassemias. Thus, thalassemias could be cured by introducing or correcting a gene into the hematopoietic compartment or a single stem cell. Initial attempts at gene transfer have proved unsuccessful due to limitations of available gene transfer vectors. The present review described the newer approaches to overcome these limitations, includes the introduction of lentiviral vectors. New approaches have also focused on targeting the specific mutation in the globin genes, correcting the DNA sequence or manipulating the development in DNA translocation and splicing to restore globin chain synthesis. This review mainly discusses the gene therapy strategies for the thalassemias, including the use of lentiviral vectors, generation of induced pluripotent stem (iPS cells, gene targeting, splice-switching and stop codon readthrough.

  5. Recent advances in gene therapy for thalassemia.

    Science.gov (United States)

    Raja, J V; Rachchh, M A; Gokani, R H

    2012-07-01

    Thalassemias are genetically transmitted disorders. Depending upon whether the genetic defects or deletion lies in transmission of α or β globin chain gene, thalassemias are classified into α and β-thalassemias. Thus, thalassemias could be cured by introducing or correcting a gene into the hematopoietic compartment or a single stem cell. Initial attempts at gene transfer have proved unsuccessful due to limitations of available gene transfer vectors. The present review described the newer approaches to overcome these limitations, includes the introduction of lentiviral vectors. New approaches have also focused on targeting the specific mutation in the globin genes, correcting the DNA sequence or manipulating the development in DNA translocation and splicing to restore globin chain synthesis. This review mainly discusses the gene therapy strategies for the thalassemias, including the use of lentiviral vectors, generation of induced pluripotent stem (iPS) cells, gene targeting, splice-switching and stop codon readthrough.

  6. High-spin states in /sup 79/Kr populated by the /sup 78/Se(. cap alpha. ,3n) reaction and interpreted in terms of a quasiparticle-plus-rotor model

    Energy Technology Data Exchange (ETDEWEB)

    Behar, M.; Filevich, A.; Macchiavelli, A.O.; Szybisz, L.; Thieberger, P.

    1982-10-01

    Nuclear states of /sup 79/Kr were studied through the /sup 78/Se(..cap alpha..,3n) reaction at an energy of 45 MeV. Excitation functions, ..gamma..-ray angular distributions and ..gamma..-..gamma.. coincidences were performed. Three bands based on the g.s. (1/2/sup -/), 147.1 keV (5/2/sup -/) and 129.7 keV (7/2/sup +/) states, were identified. Leading order analysis and quasiparticle-plus-rotor model calculations were performed. A good overall agreement was found between the experimental data and the theoretical predictions.

  7. Application of full automated capillary electrophoresis system in the analysis of neonatal alpha thalassemia%全自动毛细管电泳仪在新生儿α珠蛋白生成障碍性贫血筛查中的应用

    Institute of Scientific and Technical Information of China (English)

    万志丹; 黄湘; 吴学威; 李冬秀; 郑国兵; 姚英姿; 梁睿

    2012-01-01

    目的 探讨全自动毛细管电泳仪在新生儿α珠蛋白生成障碍性贫血筛查中的应用价值.方法使用全自动毛细管电泳仪对45 863例新生儿脐血标本进行血红蛋白(Hb)电泳分析,检测HbA、HbF、HbA2和异常Hb的含量,对筛查表型阳性的病例召回进行基因分析.结果 45 863例新生儿脐血标本中检测出巴特血红蛋白(Hb Bart′s)阳性者2 964例,筛查阳性率6.46%(2 964/45 863);召回其中1 278例行基因分析,1 173例确诊为α珠蛋白基因缺失,符合率91.8%.确诊病例以标准型为主,占64.4%;基因分型以--SEA/αα最为常见.静止型的Hb Bart′s含量95%置信区间为0.13%~0.97%,标准型Hb Bart′s含量95%置信区间为1.28%~5.92%,HbH病Hb Bart′s含量95%置信区间为8.32%~30.28%,Hb Bart′s水肿胎Hb Bart′s含量高于80%.结论 全自动毛细管电泳分析技术与基因分析有良好的一致性,根据Hb Bart′s含量的多少可初步进行α珠蛋白生成障碍性贫血的临床分型.%Objective To assess capillary electrophoresis system in the analysis of neonatal alpha thalassemia. Methods Using automatic capillary electrophoresis instrument to analyze 45 863 cases of neonatal cord hemoglobin(Hb) electrophoresis to detect HbA,HbF,HbA2 and abnormal Hb content,and the positive phenotypes cases were recalled for genetic analysis. Results Amongall 45 863 cases of neonatal cord specimens,6. 46%(2 964/45 863) were with Hb Bart s. 1 278 positive cases were recalled for gene detection, among which 1 173 patients were alpha globin gene deletion, with coincidence rate 91. 8%. Most confirmed cases werestandard type,about 64. 5 % ,and genotyping of-SEA/aawas the most common. The 95% range of Hb Bart s content in statictype was 0. 13% - 0.97%,in standard type was 1.28% -5. 92% and in HbH disease was 8. 32% -30. 28%. In Hb Bart's fetal e dema,the content of Hb Bart s was more than 80%. Conclusion Automatic capillary electrophoresis might be with great consis tence with

  8. INFECTIONS IN THALASSEMIA AND HEMOGLOBINOPATHIES

    Directory of Open Access Journals (Sweden)

    Deborah Rund

    2009-06-01

    Full Text Available

     

    The clinical approach to thalassemia and hemoglobinopathies, specifically Sickle Cell Disease (SCD, based on transfusions, iron chelation and bone marrow transplantation has ameliorated their prognosis. Nevertheless, infections still may cause serious complications in these patients. The susceptibility to infections in thalassemia and SCD arises both from a large spectrum of immunological abnormalities and from exposure to specific infectious agents. Four fundamental issues will be focused upon as central causes of immune dysfunction: the diseases themselves; iron overload, transfusion therapy and the role of the spleen. Thalassemia and SCD differ in their pathogenesis and clinical course. It will be outlined how these differences affect immune dysfunction, the risk of infections and the types of most frequent infections in each disease. Moreover, since transfusions are a fundamental tool for treating these patients, their safety is paramount in reducing the risks of infections. In recent years, careful surveillance worldwide and improvements in laboratory tests reduced greatly transfusion transmitted infections, but the problem is not completely resolved. Finally, selected topics will be discussed regarding Parvovirus B19 and transfusion transmitted infections as well as the prevention of infectious risk postsplenectomy or in presence of functional asplenia.

  9. A Randomized Multicentre Phase II Trial Comparing Adjuvant Therapy in Patients with Interferon Alpha-2b and 5-FU Alone or in Combination with Either External Radiation Treatment and Cisplatin (CapRI or Radiation alone regarding Event-Free Survival – CapRI-2

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    Friess Helmut

    2009-05-01

    Full Text Available Abstract Background The 5-year survival of patients with resected pancreatic adenocarcinoma is still unsatisfying. The ESPAC-1 and the CONKO 001 trial proofed that adjuvant chemotherapy improves 5-year survival significantly from approximately 14% to 21%. In parallel, investigators from the Virginia Mason Clinic reported a 5-year survival rate of 55% in a phase II trial evaluating a combination of adjuvant chemotherapy, immunotherapy and external beam radiation (CapRI-scheme. Two other groups confirmed in phase II trials these results to a certain extent. However, these groups reported severe gastrointestinal toxicity (up to 93% grade 3 or 4 toxicity. In a randomized controlled phase III trial, called CapRI, 110 patients were enrolled from 2004 to 2007 in Germany and Italy to check for reproducibility. Interestingly, much less gastrointestinal toxicity was observed. However, dose-reduction due to haematological side effects had to be performed in nearly all patients. First clinical results are expected for the end of 2009. Methods/Design CapRI-2 is an open, controlled, prospective, randomized, multicentre phase II trial with three parallel arms. A de-escalation of the CapRI-scheme will be tested in two different modifications. Patients in study arm A will be treated as outpatients with the complete CapRI-scheme consisting of cisplatin, Interferon alpha-2b and external beam radiation and three cycles of 5-fluorouracil continuous infusion. In study arm B the first de-escalation will be realised by omitting cisplatin. Next, patients in study arm C will additionally not receive external beam radiation. A total of 135 patients with pathologically confirmed R0 or R1 resected pancreatic adenocarcinoma are planned to be enrolled. Primary endpoint is the comparison of the treatment groups with respect to six-month event-free-survival. An event is defined as grade 3 or grade 4 toxicity, objective tumour recurrence, or death. Discussion The aim of this

  10. My Story: Real Stories of People Living with Thalassemia

    Science.gov (United States)

    ... Share Compartir Real Stories from People living with Thalassemia On this Page Rahul's Story Aaron's Story Rahul's ... is Rahul Kapoor, and I was born with thalassemia, a blood disorder which requires transfusions every other ...

  11. What Are the Signs and Symptoms of Thalassemias?

    Science.gov (United States)

    ... Twitter. What Are the Signs and Symptoms of Thalassemias? A lack of oxygen in the bloodstream causes ... especially with bones in the face) Complications of Thalassemias Better treatments now allow people who have moderate ...

  12. Factors Influencing Beta-Thalassemia Awareness in Western India

    OpenAIRE

    Ashwin P Patel; Prakash H Parmar; Rupesh B Patel; Nikhil M Trivedi; Nileshkumar A Bhartiya

    2016-01-01

    "Context: Beta-thalassemia is highly prevalent in western India. Our organization runs a screening and prevention program to create awareness and reduce the incidence of homozygous beta-thalassemia cases. Aims: The study was designed to evaluate factors influencing awareness about Beta-thalassemia. Methodology: This cross sectional survey was conducted at six colleges, two medical clinics, and a thalassemia transfusion centre. It involved 398 adults ( and #8805;18 years).The survey form...

  13. Cytochrome P450c17 (steroid 17. cap alpha. -hydroxylase/17,20 lyase): cloning of human adrenal and testis cDNAs indicates the same gene is expressed in both tissues

    Energy Technology Data Exchange (ETDEWEB)

    Chung, B.; Picado-Leonard, J.; Haniu, M.; Bienkowski, M.; Hall, P.F.; Shively, J.E.; Miller, W.L.

    1987-01-01

    P450c17 is the single enzyme mediating both 17..cap alpha..-hydroxylase (steroid 17..cap alpha..-monooxygenase, EC 1.14.99.9) and 17,20 lyase activities in the synthesis of steroid hormones. It has been suggested that different P450c17 isozymes mediate these activities in the adrenal gland and testis. The authors sequenced 423 of the 509 amino acids (83%) of the porcine adrenal enzyme; based on this partial sequence, a 128-fold degenerate 17-mer was synthesized and used to screen a porcine adrenal cDNA library. This yielded a 380-base cloned cDNA, which in turn was used to isolate several human adrenal cDNAs. The longest of these, lambda hac 17-2, is 1754 base pairs long and includes the full-length coding region, the complete 3'-untranslated region, and 41 bases of the 5'-untranslated region. This cDNA encodes a protein of 508 amino acids having a predicted molecular weight of 57,379.82. High-stringency screening of a human testicular cDNA library yielded a partial clone containing 1303 identical bases. RNA gel blots and nuclease S1-protection experiments confirm that the adrenal and testicular P450c17 mRNAs are indistinguishable. These data indicate that the testis possesses a P450c17 identical to that in the adrenal. The human amino acid sequence is 66.7% homologous to the corresponding regions of the porcine sequence, and the human cDNA and amino acid sequences are 80.1 and 70.3% homologous, respectively, to bovine adrenal P450c17 cDNA. Both comparisons indicate that a central region comprising amino acid residues 160-268 is hypervariable among these species of P450c17.

  14. Thalassemia

    Science.gov (United States)

    ... form of hemoglobin. Hemoglobin is the protein in red blood cells that carries oxygen. The disorder results in large numbers of red blood cells being destroyed, which leads to anemia. Causes Hemoglobin ...

  15. Death cap

    DEFF Research Database (Denmark)

    Rudbæk, Torsten R; Kofoed, Pernille Bouteloup; Bove, Jeppe

    2014-01-01

    Death cap (Amanita phalloides) is commonly found and is one of the five most toxic fungi in Denmark. Toxicity is due to amatoxin, and poisoning is a serious medical condition, causing organ failure with potential fatal outcome. Acknowledgement and clarification of exposure, symptomatic and focused...

  16. Beliefs about chelation among thalassemia patients

    Directory of Open Access Journals (Sweden)

    Trachtenberg Felicia L

    2012-12-01

    Full Text Available Abstract Background Understanding patients’ views about medication is crucial to maximize adherence. Thalassemia is a congenital blood disorder requiring chronic blood transfusions and daily iron chelation therapy. Methods The Beliefs in Medicine Questionnaire (BMQ was used to assess beliefs in chelation in thalassemia patients from North America and London in the Thalassemia Longitudinal Cohort (TLC of the Thalassemia Clinical Research Network (TCRN. Chelation adherence was based on patient report of doses administered out of those prescribed in the last four weeks. Results Of 371 patients (ages 5-58y, mean 24y, 93% were transfused and 92% receiving chelation (26% deferoxamine (DFO; a slow subcutaneous infusion via portable pump, 63% oral, 11% combination. Patients expressed high “necessity” for transfusion (96%, DFO chelation (92% and oral chelation (89%, with lower “concern” about treatment (48%, 39%, 19% respectively. Concern about oral chelation was significantly lower than that of DFO (p Conclusions Despite their requirement for multimodal therapy, thalassemia patients have positive views about medicine, more so than in other disease populations. Patients may benefit from education about the tolerability of chelation and strategies to effectively cope with side effects, both of which might be beneficial in lowering body iron burden. Clinicaltrials.gov identifier NCT00661804

  17. Future alternative therapies for β-thalassemia.

    Science.gov (United States)

    Rivella, Stefano; Rachmilewitz, Eliezer

    2009-12-01

    β-thalassemia is an inherited disorder due to mutations found in the β-globin gene, leading to anemia and requiring sporadic or chronic blood transfusions for survival. Without proper chelation, β-thalassemia results in iron overload. Ineffective erythropoiesis can lead to iron overload even in untransfused patients who are affected by β-thalassemia intermedia. Better understanding of the molecular biologic aspects of this disorder has led to improvements in population screening and prenatal diagnosis, which, in turn, have led to dramatic reductions in the number of children born with β-thalassemia major in the Mediterranean littoral. However, as a consequence of decreases in neonatal and childhood mortality in other geographical areas, β-thalassemia has become a worldwide clinical problem. A number of unsolved pathophysiological issues remain, such as ineffective erythropoieis, abnormal iron absorption, oxidative stress, splenomegaly and thrombosis. In the last few years, novel studies have the potential to introduce new therapeutic approaches that might reduce these problems and limit the need for blood transfusion.

  18. Phase III trial of postoperative cisplatin, interferon alpha-2b, and 5-FU combined with external radiation treatment versus 5-FU alone for patients with resected pancreatic adenocarcinoma – CapRI: study protocol [ISRCTN62866759

    Directory of Open Access Journals (Sweden)

    Schmitz-Winnenthal H

    2005-04-01

    Full Text Available Abstract After surgical intervention with curative intention in specialised centres the five-year survival of patients with carcinoma of the exocrine pancreas is only 15%. The ESPAC-1 trial showed an increased five-year survival of 21% achieved with adjuvant chemotherapy. Investigators from the Virginia Mason Clinic have reported a 5-year survival rate of 55% in a phase II trial evaluating adjuvant chemotherapy, immunotherapy and external-beam radiation. Design The CapRI study is an open, controlled, prospective, randomised multi-centre phase III trial. Patients in study arm A will be treated as outpatients with 5-Fluorouracil; Cisplatin and 3 million units Interferon alpha-2b for 5 1/2 weeks combined with external beam radiation. After chemo-radiation the patients receive continuous 5-FU infusions for two more cycles. Patients in study arm B will be treated as outpatients with intravenous bolus injections of folinic acid, followed by intravenous bolus injections of 5-FU given on 5 consecutive days every 28 days for 6 cycles. A total of 110 patients with specimen-proven R0 or R1 resected pancreatic adenocarcinoma will be enrolled. An interim analysis for patient safety reasons will be done one year after start of recruitment. Evaluation of the primary endpoint will be performed two years after the last patients' enrolment. Discussion The aim of this study is to evaluate the overall survival period attained by chemo-radiotherapy including interferon alpha 2b administration with adjuvant chemotherapy. The influence of interferon alpha on the effectiveness of the patients' chemoradiation regimen, the toxicity, the disease-free interval and the quality of life are analysed. Different factors are tested in terms of their potential role as predictive markers.

  19. Transfusion regimens in thalassemia intermedia

    Directory of Open Access Journals (Sweden)

    Z. Karakas

    2011-12-01

    Full Text Available Thalassemia intermedia (TI is a heterogeneous disease, in terms of both clinical manifestations and underlying molecular defects. Some TI patients are asymptomatic until adult life, whereas others are symptomatic from early childhood. In contrast with patients with Thalassemia major (TM, the severity of anemia is less and the patients do not require transfusions during at least the first few years of life. Many patients with TI, especially older ones, have been exposed to the multiple long-term effects of chronic anemia and tissue hypoxia and their compensatory reactions, including enhanced erythropoiesis and increased iron absorption. Bone marrow expansion and extramedullary hematopoiesis lead to bone deformities and liver and spleen enlargement. Therapeutic strategies in TI are not clear and different criteria are used to decide the initiation of transfusion and chelation therapy, modulation of fetal hemoglobin production, and hematopoietic stem cell transplantation on an individual basis. The clinical picture of well-treated TM patients with regular transfusionchelation therapy is better from TI patients who have not received adequate transfusion therapy. There is a significant role of early blood transfusion to prevent and treat complications commonly associated with TI, such as extramedullary erythropoiesis and bone deformities, autoimmune hemolytic anemia, leg ulcers, gallstones, pseudoxantoma elasticum, hyperuricosuria, gout and pulmonary hypertension, which are rarely seen in thalassemia major. Nowadays, indications of transfusion in patients with TI are chronic anemia (Hb < 7 g/dL, bone deformities, growth failure, extramedullary erythropoiesis, heart failure, pregnancy and preparation for surgical procedures. Conclusion: Adequate (regular or tailored transfusion therapy is an important treatment modality for increasing the quality of life in patients with thalassemia intermedia during childhood. 就临床表象和潜在的分子缺

  20. Apical cap

    Energy Technology Data Exchange (ETDEWEB)

    McLoud, T.C.; Isler, R.J.; Novelline, R.A.; Putman, C.E.; Simeone, J.; Stark, P.

    1981-08-01

    Apical caps, either unilateral or bilateral, are a common feature of advancing age and are usually the result of subpleural scarring unassociated with other diseases. Pancoast (superior sulcus) tumors are a well recognized cause of unilateral asymmetric apical density. Other lesions arising in the lung, pleura, or extrapleural space may produce unilateral or bilateral apical caps. These include: (1) inflammatory: tuberculosis and extrapleural abscesses extending from the neck; (2) post radiation fibrosis after mantle therapy for Hodgkin disease or supraclavicular radiation in the treatment of breast carcinoma; (3) neoplasm: lymphoma extending from the neck or mediastinum, superior sulcus bronchogenic carcinoma, and metastases; (4) traumatic: extrapleural dissection of blood from a ruptured aorta, fractures of the ribs or spine, or hemorrhage due to subclavian line placement; (5) vascular: coarctation of the aorta with dilated collaterals over the apex, fistula between the subclavian artery and vein; and (6) miscellaneous: mediastinal lipomatosis with subcostal fat extending over the apices.

  1. Ineffective Erythropoiesis in β-Thalassemia

    Directory of Open Access Journals (Sweden)

    Jean-Antoine Ribeil

    2013-01-01

    Full Text Available In humans, β-thalassemia dyserythropoiesis is characterized by expansion of early erythroid precursors and erythroid progenitors and then ineffective erythropoiesis. This ineffective erythropoiesis is defined as a suboptimal production of mature erythrocytes originating from a proliferating pool of immature erythroblasts. It is characterized by (1 accelerated erythroid differentiation, (2 maturation blockade at the polychromatophilic stage, and (3 death of erythroid precursors. Despite extensive knowledge of molecular defects causing β-thalassemia, less is known about the mechanisms responsible for ineffective erythropoiesis. In this paper, we will focus on the underlying mechanisms leading to premature death of thalassemic erythroid precursors in the bone marrow.

  2. Molecular identification of Sicilian (dߺ-thalassemia associated with ß-thalassemia and hemoglobin S in Brazil

    Directory of Open Access Journals (Sweden)

    Andrade T.G. de

    2002-01-01

    Full Text Available We describe the clinical and molecular characteristics of two unrelated Brazilian families with an association of the Sicilian form of (deltaߺ-thalassemia with hemoglobin S and ß-thalassemia. Direct sequencing of the ß-globin gene showed only the hemoglobin S mutation in patient 1 and the ß-thalassemia IVS1-110 in patient 2. The other allele was deleted in both patients and PCR of DNA samples of the breakpoint region of both patients showed a band of approximately 1,150 bp, expected to be observed in the DNA of carriers of Sicilian (deltaߺ-thalassemia. The nucleotide sequence of this fragment confirmed the Sicilian deletion. There are few reports concerning the Hb S/(deltaߺ-thalassemia association and patient 2 is the first reported case of Sicilian type of (deltaߺ-thalassemia in association with ß-thalassemia documented at the molecular level.

  3. 基于社区水平的珠海市大人群地中海贫血的遗传筛查和产前诊断%A community-based genetic screening of large-scale population and prenatal diagnosis for alpha and beta thalassemia in Zhuhai city of Guangdong province

    Institute of Scientific and Technical Information of China (English)

    周玉球; 徐湘民; 莫秋华; 卢金汉; 李莉艳; 梁雄; 贾世奇; 肖鸽飞; 周万军; 肖奇志

    2008-01-01

    Objective To describe a community-based model for prevention and control of severe α and β thalassemias in Zhuhai city of Guangdong province.Methods Couples for premarital medical examination or regular heahhcare examination in pregnancy were enrolled in this prospective screening program,which was supported by the two-level network composed of 6 local hospitals for testing thalassemias and follow-up for genetic counseling.A conventional heterozygote screening strategy Was used to determine α and β thalasemia traits in women and their partners according to the standard procedures of hematological phenotype analysis.Then confirmative diagnosis of α and β thalassemia was performed On those couples suspected at-risk for seven thalassemia by using the PCR-based molecular diagnostic assays. The couples at risk for severe thalassemia Were counseled and offered prenatal diagnosis and termination of pregnancy in ease of an affected fetus. Results During the period between January 1998 and December 2005, the screened records included 85522 young females and their partners for premarital screening and 10439 pregnant women for prenatal screening,with 71.38% coverage of total population recorded in this city for premarital screening.Six thousands five hundreds and sixty-three individuals in total were found to be the carriers of thalassemias,with 4312 for α thalassemia (4.5%) and 2251 for β thalassemia (2.3%),respectively.One hundred and forty-eisht couples Were diagnosed to be at-risk for thalassemias,including 103 for a thalassemia and 45 for β thalassemia, respectively.Successful prenatal diagnosis was made for 142(98 for a thalasemia and 44 for β thalassemia) out of 148 (95.9%) pregnancies at-risk for severe thalassemias.Twenty-three cases of hydrops fetalis,4 of Hb H diseases and 14 of β thal assemia were identified.All 41 pregnancies with affected fetuses were voluntarily terminated.Thus, this has led to a marked decrease of scvcrc thalassemia syndrome since

  4. Mammalian CAP interacts with CAP, CAP2, and actin.

    Science.gov (United States)

    Hubberstey, A; Yu, G; Loewith, R; Lakusta, C; Young, D

    1996-06-01

    We previously identified human CAP, a homolog of the yeast adenylyl cyclase-associated protein. Previous studies suggest that the N-terminal and C-terminal domains of CAP have distinct functions. We have explored the interactions of human CAP with various proteins. First, by performing yeast two-hybrid screens, we have identified peptides from several proteins that interact with the C-terminal and/or the N-terminal domains of human CAP. These peptides include regions derived from CAP and BAT3, a protein with unknown function. We have further shown that MBP fusions with these peptides can associate in vitro with the N-terminal or C-terminal domains of CAP fused to GST. Our observations indicate that CAP contains regions in both the N-terminal and C-terminal domains that are capable of interacting with each other or with themselves. Furthermore, we found that myc-epitope-tagged CAP coimmunoprecipitates with HA-epitope-tagged CAP from either yeast or mammalian cell extracts. Similar results demonstrate that human CAP can also interact with human CAP2. We also show that human CAP interacts with actin, both by the yeast two-hybrid test and by coimmunoprecipitation of epitope-tagged CAP from yeast or mammalian cell extracts. This interaction requires the C-terminal domain of CAP, but not the N-terminal domain. Thus CAP appears to be capable of interacting in vivo with other CAP molecules, CAP2, and actin. We also show that actin co-immunoprecipitates with HA-CAP2 from mammalian cell extracts.

  5. Reactor neutron activation analysis for aluminium in the presence of phosphorus and silicon. Contributions of /sup 28/Al activities from /sup 31/P (n,. cap alpha. ) /sup 28/Al and /sup 28/Si (n,p) /sup 28/Al reactions

    Energy Technology Data Exchange (ETDEWEB)

    Mizumoto, Yoshihiko (Kinki Univ., Higashi-Osaka, Osaka (Japan). Faculty of Science and Technology); Iwata, Shiro; Sasajima, Kazuhisa; Yoshimasu, Fumio; Yase, Yoshiro

    1984-01-01

    Reactor neutron activation analysis for aluminium in samples containing phosphorus and silicon was studied. The experiments were performed by using pneumatic tube of the Kyoto University Reactor (KUR). At first, the ratios of the /sup 28/Al activity produced from /sup 27/Al(n, ..gamma..) /sup 28/Al reaction by thermal neutrons to that from /sup 31/P(n, ..cap alpha..)/sup 28/Al reaction by fast neutrons, and to that from /sup 28/Si(n, p)/sup 28/Al reaction were measured by ..gamma..-ray spectrometry. With a ratio of about 5 for the thermal to fast neutron flux of KUR, the ratio of the /sup 28/Al activity from aluminium to that from phosphorus was to be 812 +- 7, and to that from silicon 282 +- 3. Secondly, the contributions of /sup 28/Al activities from phosphorus and silicon and the determination limit of aluminium were calculated for various parameters, such as fast neutron flux, thermal to fast neutron flux ratio, amounts of phosphorus and silicon, etc. Thirdly, on the basis of these results, aluminium contents in spinal cords and brains of amyotrophic lateral sclerosis, Parkinsonism-dementia complex and control cases were determined.

  6. Physiology and Pathophysiology of Iron Cardiomyopathy in Thalassemia

    OpenAIRE

    2005-01-01

    Iron cardiomyopathy remains the leading cause of death in patients with thalassemia major. Magnetic resonance imaging (MRI) is ideally suited for monitoring thalassemia patients because it can detect cardiac and liver iron burdens as well as accurately measure left ventricular dimensions and function. However, patients with thalassemia have unique physiology that alters their normative data. In this article, we review the physiology and pathophysiology of thalassemic heart disease as well as ...

  7. Premature epiphyseal fusion and extramedullary hematopoiesis in thalassemia

    Energy Technology Data Exchange (ETDEWEB)

    Colavita, N.; Orazi, C.; Danza, S.M.; Falappa, P.G.; Fabbri, R.

    1987-10-01

    The main skeletal abnormalities in ..beta..-thalassemia are widening of medullary spaces, rarefaction of bone trabeculae, thinning of cortical bone, and perpendicular periosteal spiculation. Premature epiphyseal fusion (PEF) and extramedullary hematopoiesis (EH) are found, though more rarely. The incidence of PEF and EH in 64 patients affected by ..beta..-thalassemia is reported. The different incidence of such complications in thalassemia major and intermedia is reported, and a possible correlation with transfusion regimen is also considered.

  8. Quality of life in thalassemia major: Reliability and validity of the Persian version of the SF-36 questionnaire

    Directory of Open Access Journals (Sweden)

    Jafari H

    2008-01-01

    Full Text Available Aims: The objective of this study was to determine the reliability and validity of the eight-item Short Form Health Survey (SF-36 questionnaire translated into Persian for use in Iranian patients with thalassemia major. Materials and Methods: Using a standard "forward-backward" translation procedure, the English language version of the questionnaire was translated into Persian. Two hundred patients with thalassemia major following up at the Thalassemia Center, Dastgheib Hospital, Shiraz, Iran, were enrolled in this study. Statistical Analysis: The reliability and internal consistency of the questionnaire were assessed by Cronbach′s alpha coefficient and Spearman′s correlation, respectively. Validity was assessed using convergent and discriminant validity. Results: The mean age of 200 subjects enrolled in the study was 19.81+/-4.07 years. Reliability analysis showed satisfactory results (Cronbach′s a coefficient = 0.915. The factor analysis showed that all items were in the same groups as previous studies with the exception of role emotional and general health that had been substituted. Most of the patients were in lower range of normal for both mental and physical summary status. Conclusions: The study finding showed that the Persian version of SF-36 questionnaire has a good structural characteristic and is a reliable and valid instrument for measuring the quality of life of patients with thalassemia major.

  9. Antioxidant status in beta thalassemia major: A single-center study

    Directory of Open Access Journals (Sweden)

    Faiza Waseem

    2011-01-01

    Full Text Available Background: Homozygous β thalassemia may lead to a marked reduction or absence of normal β chain production and accumulation of unpaired alpha-globin chains. A crucial component in the oxidant susceptibility of the thalassemic RBC is the release of heme and iron from the excessive, unpaired α-globin chains. This release can initiate self-amplifying redox reactions, which deplete the cellular reduction potential (e.g., GSH, oxidize additional hemoglobin and accelerate RBC destruction. Furthermore, β-thalassemia patients are under continuous blood transfusion, which, although life-saving, leads to an iron overload with a resultant increase in non-transferrin-bound iron that may cause greater tissue toxicity than iron in other forms. Iron-induced oxidative stress is known to be one of the most important factors determining cell injury in thalassemic patients. Therefore, we designed this study to obtain a comprehensive picture of the iron overload, antioxidant status and cell damage in β thalassemia major patients undergoing regular blood transfusion. Materials and Methods: A total of 48 diagnosed patients of β thalassemia major and 30 age- and sex-matched healthy subjects were included in the study. Estimation of hemoglobin, hematocrit, glutathione peroxidase (GPX, superoxide dismutase (SOD,vitamin E, serum ferritin, total and direct bilirubin, AST and ALT was carried out. Results: The levels of vitamin E, antioxidant enzymes GPX and SOD were significantly lowered in β thalassemic patients as compared with the control group (P<0.001. Serum total and direct bilirubin, AST and ALT were significantly elevated in thalassemic subjects as compared with the control group, indicating liver cell damage. Conclusion: Thus, our findings indicate that thalassemics are in a state of enhanced oxidative stress and that the administration of selective antioxidants would represent a promising approach toward counteracting oxidative damage and its deleterious

  10. Palmar Dermatoglyphics in Patients of Thalassemia Major

    Directory of Open Access Journals (Sweden)

    Rashida H Andani

    2012-06-01

    Full Text Available Introduction: Dermatoglyphics have proven to be a helpful tool in identifying specific syndromes of genetic origins. Any epidermal ridge alterations in individuals may have a distinctive dermatoglyphic feature. An attempt has been made to find out any significant variation in-patient of Thalassemia major, so it can be highlighted with a view to assess its value as a diagnostic marker. Methodology: Palm prints of 100 diagnosed patients of Thalassemia were studied and study matched with 100 healthy subjects. Results: The preset study shows autosomal recessive inheritance caused by a single mutant gene. The chain is coded by gene on chromosome no-16 &gene on chromosome No-11; unusual dermatoglyphics are reported in-patient with single gene disorders. Thalassemia is also a single gene disorder so it too can be added to this list. Parameters studied were ‘atd’ angle, ‘a-b’ ridge count and main line index. It was observed that the ‘atd’ angle wider in patients in comparison to control group, which indicates distal displacement of axial tri-radius. It was also found that more number of patients fell under the group of high ridge count. The difference was significant statistically for right hand. Low main line index was observed in patients which indicates vertical alignment of ridges. Conclusion: The deviation of the different dermatoglyphic features in patients of Thalassemia major provides a single, inexpensive method of clinical observation and adds another new diagnostic tool to the clinicians. [National J of Med Res 2012; 2(3.000: 287-290

  11. Management of beta-thalassemia-associated osteoporosis.

    Science.gov (United States)

    Giusti, Andrea; Pinto, Valeria; Forni, Gian Luca; Pilotto, Alberto

    2016-03-01

    Beta-Thalassemia-associated osteoporosis is a multifactorial and complex condition. Different acquired and genetic factors are involved in its pathogenesis. These factors produce an imbalance in bone remodeling by inhibiting osteoblast activity and increasing osteoclast function, leading to bone loss and increased fracture risk. The management of patients presenting with thalassemia-associated osteoporosis should consist of the implementation of general measures and the prescription of a specific pharmacological agent, with the aim of reducing fracture risk and preventing disability and deterioration of quality of life. General measures include control of anemia, adequate chelation therapy, healthy nutrition and lifestyle, regular exercise, adequate management of comorbid conditions, hormone replacement therapy in patients with hypogonadism, and vitamin D supplementation/therapy. Among the pharmacological agents currently available for the management of osteoporosis in postmenopausal women and men, bisphosphonates have been shown to improve bone mineral density, to reduce bone turnover, and to decrease bone/back pain in patients with thalassemia-associated osteoporosis, with a good profile of safety and tolerability. On the other hand, there are limited experiences with other pharmacological agents (e.g., denosumab or teriparatide). The complexity of this condition presents diagnostic and therapeutic challenges and underscores the importance of a comprehensive and multidisciplinary approach.

  12. Increased knowledge of thalassemia promotes early carrier status examination among medical students

    Directory of Open Access Journals (Sweden)

    Julius Broto Dewanto

    2016-04-01

    A higher thalassemia knowledge score causes medical students to be willing to undergo thalassemia carrier status examination at an earlier point in timing. A well-organized educational program focusing on thalassemia and early screening in young adults may enhance the thalassemia prevention program.

  13. Synthesis of tritiated 1-alpha-methadol and 1-alpha-acetylmethadol

    Energy Technology Data Exchange (ETDEWEB)

    Thang, D.C.; Nam, N.H.; Pontikis, R. (Institut National de la Sante et de la Recherche Medicale (INSERM), Hopital Fernand Widal, 75 - Paris (France)); Pichat, L. (CEA Centre d' Etudes Nucleaires de Saclay, 91 - Gif-sur-Yvette (France). Service des Molecules Marquees)

    1982-04-01

    dl-Methadone was resolved by crystallization of its ammonium d- ..cap alpha.. -bromocamphor-..pi..-sulfonate salt to give d-methadone. The latter in ethyl acetate solution was reduced with tritium gas to 1-..cap alpha..-methadol /sup 3/H in presence of Adams platinum oxide at normal temperature and pressure. Acetylation of 1-..cap alpha..-carbinol hydrochloride by means of acetyl chloride afforded 1-..cap alpha..-acetylmethadol /sup 3/H, specific activity: 20 Ci/mMole. The positions and extent of tritium labelling were determined by /sup 3/H NMR spectroscopy.

  14. Utilization of denaturing gradient gel electrophoresis for diagnosis of {beta}-thalassemia and ascertainment of new mutations

    Energy Technology Data Exchange (ETDEWEB)

    Ngo, K.Y.; Liu, D.; Lee, J. [Univ. of California, San Diego (United States)] [and others

    1994-09-01

    During the past two years we have tested 2,300 Southeast Asians for alpha- and beta-thaleassemia mutations. We found the incidence of hemoglobin E ({beta}{sup 26}) to be 47% among Laotians and 38% among Cambodians. The incidence of beta thalassemia trait is 9% for Laotians and 6% for Cambodians. Thus, the risk for hemoglobin E/{beta}{sup 26} thalassemia, a transfusion-dependent disorder, is increased in these two population groups. Denaturing gradient gel electrophoresis (DGGE) has proven to be useful in testing for beta-thalassemia carriers and identifying new mutations in the beta globin gene. DNA was extracted from venous blood obtained from patients with elevated Hgb A2 (>4%). Five DNA fragments, encompassing the beta globin gene cluster, were amplified by PCR and analyzed, along with known beta gene mutations as controls, by DGGE using different denaturing gradient concentrations. Different mutations at the same nucleotide position can be distinguished by migration pattern on the DGGE (e.g., in IVS-I-1, G{r_arrow}A and T). Compound heterozygotes for {beta}-thalassemia can be detected on the same gel (e.g., HbE/mutation codon 17). New mutations are identified by their migration pattern compared with controls and determined by subsequent sequencing. We have identified three new mutations: codon 82 CAA{r_arrow}AAA in one Cambodian patient; IVS-II-667, T{r_arrow}C and IVS-II-672, A{r_arrow}C in two Laotian patients. When the parent`s genotypes are known, prenatal diagnosis can be obtained within 24 hours. Thus, PCR/DGGE combination is a rapid and reliable diagnostic approach to clinically significant {beta}-thalassemia. The most important steps are carefully designed primers and predetermined gradient concentrations for DGGE.

  15. β-Thalassemia and Polycythemia vera : Targeting chronic stress erythropoiesis

    NARCIS (Netherlands)

    Crielaard, Bart J; Rivella, Stefano

    2014-01-01

    β-Thalassemia and Polycythemia vera are genetic disorders which affect the synthesis of red blood cells, also referred to as erythropoiesis. Although essentially different in clinical presentation - patients with β-thalassemia have an impairment in β-globin synthesis leading to defective erythrocyte

  16. Frequency of Thalassemia in Iran and Khorasan Razavi

    Directory of Open Access Journals (Sweden)

    Gholam Hasan Khodaei

    2013-12-01

    Full Text Available Introduction: Beta-thalassemia is the most common hereditary disease in Iran. More than two million carriers of beta-thalassemia live in Iran. Since the Iranian population is a mixture of different ethnic groups, it is necessary to determine the frequency  in the different parts of the country. Materials and Methods: This descriptive study is a cross sectional study with helping by professional groups fighting diseases in Khorasan Razavi province.   Results: In Iran, according to World Health Organization, about 4 percent of the population, are carriers of the thalassemia gene. In other words, about 2-3 million people are suffering from thalassemia minor.Now, more than 18 thousand cases of thalassemia are scattered across the country in different provinces, are different. Mazandaran, Gilan, Hormozgan, Khuzestan, kohgiloyeh, Fars, Bushehr, Sistan and Baluchestan, Kerman and Isfahan, are 10 provinces with high prevalence in our country. We have 342 cases of thalassemia major in Khorasan Razavi province.   Conclusion: Prevalence  of thalassemia in our country is 3.6%  and Iran is located on the belt of thalassemia and due to a history of consanguinity, this disease has a prevalence of 0.6% among in the provinces of Khorasan Razavi.

  17. Two alpha, three alpha and multiple heavy-ion radioactivities

    Energy Technology Data Exchange (ETDEWEB)

    Poenaru, D.N.; Ivascu, M. (Institute for Physics and Nuclear Engineering, Bucharest (Romania))

    1985-07-01

    New decay modes by spontaneous emission of two and three ..cap alpha.. particles and two identical or different heavy ions, are predicted. The analytical variant of the superasymmetric fission model is used to estimate the half lives.

  18. Prevalence of Thalassemia Trait & Iron Deficiency Anemia during Infancy in 2011–2013 in a Thalassemia Prevalent Region: North Cyprus

    Science.gov (United States)

    ŞANLIDAĞ, Burçin; ÇAĞIN, Buse; ÖZENLİ, Övgü; ŞAHALOĞLU, Özlem; DALKAN, Ceyhun; GALİP, Nilüfer; BABAYİĞİT HOCAOĞLU, Arzu; BAHÇECİLER, Nerin

    2016-01-01

    Background: Iron Deficiency Anemia (IDA) is an important health problem all around the world especially in developing countries. In the Mediterranean countries another prevelant reason of anemia is Thalassemia. Certain strategies had been established as a government policy to reduce prevalence in North Cyprus, such as pre-marital screening of Thalassemia. The prevalence of thalassemia trait has not been evaluated since then. The aim of this study was to detect the prevalence of IDA, thalassemia trait in infants under regular follow-up and to evaluate the compliance to prophylactic iron supplementation (PIS) and its effect on IDA. Methods: Healthy children admitted to Department of Pediatrics, Near East University Hospital, in 2011–2013 were included. Data of anthropometric measurements, parental thalassemia trait status, duration of PIS usage, complete blood count, ferritin levels and hemoglobin electrophoresis were collected from hospital database program. Anemic children were grouped as IDA, thalassemia trait, both IDA and thalassemia trait and others. Results: Eıghty-nine infants with a mean age 13.52±2.09 mo were included. Compliance with PIS recommendation was 85.3% and, the mean duration of iron usage was 6.44±3.18 mo. IDA and thalassemia trait were found to be 11.2% and 4.5% respectively, while 3.4% of the infants had both IDA and thalassemia trait. Conclusion: Prevalence of thalassemia trait was 7.9% demonstrating approximately a 50% decline within 5 decades. This result confirms the success of premarital screening policy in North Cyprus. In addition, prevalence of IDA was relatively low being 14.6% supporting the beneficial effect of PIS on prevention of IDA. PMID:27928530

  19. Bone Marrow Transplantation in Thalassemia (Part 2

    Directory of Open Access Journals (Sweden)

    Maryam Zakerinia

    2009-06-01

    Full Text Available During the last two decades conventional therapy has improvedthe prognosis of thalassemia. However, despite such improvementit still remains a progressive disease with treatment-relatedcomplications such as hepatitis, liver fibrosis, and cardiac disease.Bone marrow transplantation (BMT can prevent or delayprogression of the aforementioned complications. The importanceof clinical research in the field of BMT was recognizedwith the award of the 1990 Nobel Prize in Physiology andMedicine to E. Donnall Thomas, one of the pioneers of BMT inhumans. George Mathe' was a pioneer in the early developmentof clinical BMT. Mathe' and co-workers were the first to describegraft-versus-host-disease and its treatment, and the graftversus-leukemia effect in human. The first BMT for β-thalassemia major was performed successfully by Thomas andcolleagues in Seattle, in 1981. In the same year another patientwith β-thalassemia major underwent BMT in Pesaro, Italy, byLucarelli and others Since then, several hundred transplantationshave been performed worldwide, mostly in Italy. From 1991through 2007 BMT have been performed on 497 (Tehran=342,Shiraz=155 blood transfusion dependent patients with thalassemiamajor in Iran, with disease-free survival of 71-77% respectively.Because of high graft failure and high rates of graftversus-host-disease rates, BMT from alternative donors shouldbe restricted to patients who have poor life expectancies becausethey cannot receive adequate conventional treatment or becauseof alloimmunization to minor blood antigens. Beginning in theearly 1980s, it was shown that umbilical cord blood containedhigh levels of hematopoietic progenitor cells.

  20. The pregnancy outcome in patients with minor β-thalassemia

    Directory of Open Access Journals (Sweden)

    Mehran Karimi

    2011-01-01

    Full Text Available Background: β-thalassemia is the most common hereditary disease in Iran and more than 2 million carriers of the β-thalassemia mutant gene are living in this country.Objective: To determine pregnancy outcome of women with β-thalassemia minor.Materials and Methods: In this retrospective, case-control study in two universities affiliated hospitals in Shiraz, all pregnancies occurred between 2006 and 2008 were included. Patients were divided in two groups regarding the presence of β-thalassemia minor. Patients in case and control groups were matched according to maternal age, gestational age and number of previous pregnancies. Cesarean delivery, hypertensive disorders, gestational diabetes mellitus, premature rupture of membranes and preterm labor were recorded in each group and were compared using the χ2 or Fisher exact tests. Results: Overall 510 β-thalassemia minor subjects and 512 healthy controls were studied. Cases with β-thalassemia minor had significantly higher prevalence of oligohydramnios (p<0.001 and cesarean section delivery (p=0.001. There was no significant difference regarding Apgar score in 1st (p=0.65 and 5th minute (p=0.25, IUGR (p=0.073, gestational diabetes mellitus (DM (p=0.443 and preeclampsia (p=0.116 between two study groups. Conclusion: β-thalassemia minor does not significantly influence the pregnancy outcome in the negative way.

  1. Intracranial Extramedullary Hematopoiesis in Beta-Thalassemia

    Energy Technology Data Exchange (ETDEWEB)

    Karki, Bivek; Xu, Yi Kai; Wu, Yuan Kui [Nan fang Hospital, Southern Medical University, Guangzhou (China); Tamrakar, Karuna [Zhujiang Hospital, Southern Medical University, Guangzhou (China)

    2012-03-15

    Extramedullary hematopoiesis (EMH) represents tumor-like proliferation of hemopoietic tissue which complicates chronic hemoglobinopathy. Intracranial EMH is an extremely rare occurrence. Magnetic resonance imaging (MRI) offers a precise diagnosis. It is essential to distinguish EMH from other extradural central nervous system tumors, because treatment and prognosis are totally different. Herein, we report the imaging findings of beta-thalassemia in a 13-year-old boy complaining of weakness of left side of the body and gait disturbance; CT and MRI revealed an extradural mass in the right temporoparietal region.

  2. Hubungan Tipe Thalassemia β serta Polimorfisme c.-582 A>G Promotor Gen HAMP dan Status Besi thalassemia β Berat Baru

    Directory of Open Access Journals (Sweden)

    Susi Susanah

    2015-09-01

    Full Text Available Iron overload is the common cause of morbidity and mortality in severe β-thalassemia patients. Many factors influence the iron status in severe β-thalassemia. This study aimed to analyze the association of β-thalassemia type, polymorphism c.-582 A>G promotor hepcidine antimicrobacterial peptide (HAMP gene, and iron status in newly diagnosed severe β-thalassemia. A cross-sectional study was performed at Dr. Hasan Sadikin General Hospital/Faculty of Medicine, Universitas Padjadjaran Bandung from November to December 2012. Subjects were newly diagnosed severe β-thalassemia patients who were diagnosed based on clinical manifestation and laboratory examination. Subjects had not received any blood transfusion before and had normal CRP level. Transferrin saturation (TS and serum ferritin (SF levels indicate iron status. The statistical analysis was performed using t test, Mann-Whitney, and Chi square test. Twenty nine subjects were diagnosed as newly severe β-thalassemia, 24 β-thalassemia mayor and 5 with severe β-thalassemia/HbE. There was no difference in the iron status between the two types of severe β-thalassemia and between those with and without polymorphism of c.-582 A>G promotor HAMP gene in newly diagnosed severe β-thalassemia (p>0.05. In conclusiosn, the β-thalassemia type and polymorphism of c.-582 A>G promotor HAMP gene do not associate with the iron status in newly diagnosed severe β-thalassemia patients.

  3. Progress Toward the Control and Management of the Thalassemias.

    Science.gov (United States)

    Fucharoen, Suthat; Weatherall, David J

    2016-04-01

    Because of the particularly high frequency of different severe forms of both α and β thalassemia in Asia, the development of approaches for their prevention and management is particularly challenging. However, because of earlier partnerships with richer countries, so-called North/South partnerships, and help from their governments, considerable progress toward the better control of the thalassemias has been achieved in some countries. It is vital that the global health importance of the thalassemias and related disorders, by far the commonest genetic diseases, is emphasized to the appropriate international health agencies.

  4. Molecular Understanding of Non-Transfusion-Dependent Thalassemia Associated with Hemoglobin E-β-Thalassemia in Northeast Thailand.

    Science.gov (United States)

    Yamsri, Supawadee; Pakdee, Naruwat; Fucharoen, Goonnapa; Sanchaisuriya, Kanokwan; Fucharoen, Supan

    2016-01-01

    Non-transfusion-dependent thalassemia (NTDT) is associated with various forms of thalassemia and genetic modifiers. We report the molecular basis of NTDT in hemoglobin (Hb) E-β-thalassemia disease. This study was done in 73 adult patients encountered at the prenatal diagnosis center of Khon Kaen University, Northeast Thailand. Hematological parameters and Hb patterns were collected, and α- and β-globin gene mutations were determined. Multiple single-nucleotide polymorphisms (SNPs) including the rs7482144/Gγ-XmnI polymorphism, rs2297339, rs2838513, rs4895441, and rs9399137 in the HBS1L-MYB gene, rs4671393 and rs11886868 in the BCL11A gene, and G176AfsX179 in the KLF1 gene were examined. Five β0-thalassemia mutations and a severe β+-thalassemia mutation in trans to the βE gene were identified. No significant difference in hematological parameters was observed among β-thalassemia genotypes. Coinheritance of α-thalassemia was observed in 31 of the 73 subjects (42.5%). Four SNPs including Gγ-XmnI, rs2297339, rs4895441, and rs9399137 of HBS1L-MYB were found to be associated with high Hb F levels in 39 (53.4%) subjects. The molecular basis of NTDT in the remaining 3 (4.1%) cases could not be defined. These results indicate multiple genetic factors in NTDT patients and underline the importance of complete genotyping to provide proper management, make clinical predictions, and improve genetic counseling.

  5. IRON CHELATION THERAPY IN THALASSEMIA SYNDROMES

    Directory of Open Access Journals (Sweden)

    Paolo Cianciulli

    2009-06-01

    Full Text Available Transfusional hemosiderosis is a frequent complication in patients with transfusion dependent chronic diseases such as  thalassemias and severe type of sickle cell diseases. As there are no physiological mechanisms to excrete the iron contained in transfused red cells (1 unit of blood contains approximately 200 mg of iron the excess of iron is stored in various organs. Cardiomyopathy is the most severe complication covering more than 70% of the causes of death of thalassemic patients. Although the current reference standard iron chelator deferoxamine (DFO has been used clinically for over four decades, its effectiveness is limited by a demanding therapeutic regimen that leads to poor compliance. Despite poor compliance, because of the inconvenience of subcutaneous infusion, DFO improved considerably the survival and quality of life of patients with thalassemia. Deferiprone since 1998 and Deferasirox since 2005 were licensed for clinical use. The oral chelators have a better compliance because of oral use, a comparable efficacy to DFO in iron excretion and probably a better penetration to myocardial cells. Considerable increase in iron excretion was documented with combination therapy of DFO and Deferiprone. The proper use of the three chelators will improve the prevention and treatment of iron overload, it will reduce  complications, and improve survival and quality of life of transfused patients

  6. Bone marrow transplantation in patients with Thalassemia

    Directory of Open Access Journals (Sweden)

    Ghavamzadeh A

    1993-05-01

    Full Text Available During April, 1991 and September, 1993, eighteen patients with major thalassemia admitted to Shariati BMT center. Seventeen patients were transplanted were from HLA identical siblings and one from. his HLA identical father. Eleven of the donors were the known cases of minor thalassemia. The range of patients' age was within 3-10 years (with the average of 5 years and 11 months. Among them, seven patients were male and eleven were female. As the other international BMT centers, we classified our patients into three classes. Our criteria for this classification were hepatomegaly, ferretin, and liver fibrous; 60% of our patients were put in class I and 40% in class II. All of our patients revealed a GVHD (severe graft vs. host disease three weeks post-BMT as pruritus, diarrhea, and skin erythema especially in hands and feet. Two of the patients showed severe GVHD. One of the patients had chimerism after BMT. Although one year after BMT has passed, the patients is still depended on blood transfusion. One patient, despite graft rejection, died nine months post-BMT; another one died after +70 due to GVHD. During 2.5 years, the overall graft survival rate was 88% in our center

  7. GENE THERAPY IN THALASSEMIA AND HEMOGLOBINOPATHIES

    Directory of Open Access Journals (Sweden)

    Laura Breda

    2009-11-01

    Full Text Available Sickle cell disease (SCD and ß-thalassemia represent the most common hemoglobinopathies caused, respectively, by the alteration of structural features or deficient production of the ß-chain of the Hb molecule. Other hemoglobinopathies are characterized by different mutations in the α- or ß-globin genes and are associated with anemia and might require periodic or chronic blood transfusions. Therefore, ß-thalassemia, SCD and other hemoglobinopathies are excellent candidates for genetic approaches since they are monogenic disorders and, potentially, could be cured by introducing or correcting a single gene into the hematopoietic compartment or a single stem cell. Initial attempts at gene transfer of these hemoglobinopathies have proved unsuccessful due to limitations of available gene transfer vectors. With the advent of lentiviral vectors many of the initial limitations have been overcame. New approaches have also focused on targeting the specific mutation in the ß-globin genes, correcting the DNA sequence or manipulating the fate of RNA translation and splicing to restore ß-globin chain synthesis. These techniques have the potential to correct the defect into hematopoietic stem cells or be utilized to modify stem cells generated from patients affected by these disorders. This review discusses gene therapy strategies for the hemoglobinopathies, including the use of lentiviral vectors, generation of induced pluripotent stem cells (iPS cells, gene targeting, splice-switching and stop codon readthrough.

  8. Gene therapy in thalassemia and hemoglobinopathies.

    Science.gov (United States)

    Breda, Laura; Gambari, Roberto; Rivella, Stefano

    2009-11-13

    Sickle cell disease (SCD) and ß-thalassemia represent the most common hemoglobinopathies caused, respectively, by the alteration of structural features or deficient production of the ß-chain of the Hb molecule. Other hemoglobinopathies are characterized by different mutations in the α- or ß-globin genes and are associated with anemia and might require periodic or chronic blood transfusions. Therefore, ß-thalassemia, SCD and other hemoglobinopathies are excellent candidates for genetic approaches since they are monogenic disorders and, potentially, could be cured by introducing or correcting a single gene into the hematopoietic compartment or a single stem cell. Initial attempts at gene transfer of these hemoglobinopathies have proved unsuccessful due to limitations of available gene transfer vectors. With the advent of lentiviral vectors many of the initial limitations have been overcame. New approaches have also focused on targeting the specific mutation in the ß-globin genes, correcting the DNA sequence or manipulating the fate of RNA translation and splicing to restore ß-globin chain synthesis. These techniques have the potential to correct the defect into hematopoietic stem cells or be utilized to modify stem cells generated from patients affected by these disorders. This review discusses gene therapy strategies for the hemoglobinopathies, including the use of lentiviral vectors, generation of induced pluripotent stem cells (iPS) cells, gene targeting, splice-switching and stop codon readthrough.

  9. Molecular identification of Sicilian (dß)º-thalassemia associated with ß-thalassemia and hemoglobin S in Brazil

    OpenAIRE

    2002-01-01

    We describe the clinical and molecular characteristics of two unrelated Brazilian families with an association of the Sicilian form of (deltaß)º-thalassemia with hemoglobin S and ß-thalassemia. Direct sequencing of the ß-globin gene showed only the hemoglobin S mutation in patient 1 and the ß-thalassemia IVS1-110 in patient 2. The other allele was deleted in both patients and PCR of DNA samples of the breakpoint region of both patients showed a band of approximately 1,150 bp, expected to be o...

  10. Molecular Identification Of Sicilian (deltabeta) Degrees-thalassemia Associated With Beta-thalassemia And Hemoglobin S In Brazil.

    OpenAIRE

    2015-01-01

    We describe the clinical and molecular characteristics of two unrelated Brazilian families with an association of the Sicilian form of (deltabeta) degrees -thalassemia with hemoglobin S and beta-thalassemia. Direct sequencing of the beta-globin gene showed only the hemoglobin S mutation in patient 1 and the beta-thalassemia IVS1-110 in patient 2. The other allele was deleted in both patients and PCR of DNA samples of the breakpoint region of both patients showed a band of approximately 1,150 ...

  11. Molecular identification of Sicilian (deltaß)º-thalassemia associated with ß-thalassemia and hemoglobin S in Brazil

    OpenAIRE

    2002-01-01

    We describe the clinical and molecular characteristics of two unrelated Brazilian families with an association of the Sicilian form of (deltaß)º-thalassemia with hemoglobin S and ß-thalassemia. Direct sequencing of the ß-globin gene showed only the hemoglobin S mutation in patient 1 and the ß-thalassemia IVS1-110 in patient 2. The other allele was deleted in both patients and PCR of DNA samples of the breakpoint region of both patients showed a band of approximately 1,150 bp, expected to be o...

  12. Study on Mössbauer spectra of hemoglobin in thalassemia

    Science.gov (United States)

    Xuanhui, Guo; Nanming, Zhao; Xiufang, Zhang; Naifei, Gao; Youwen, Huang; Rongxin, Wang

    1988-02-01

    The57Fe Mössbauer spectra of erythrocytes in normal subjects and nine patients of different thalassemias were studied. Together with clinical analysis, the correlation between the components in the spectra and different types of anemias was discussed.

  13. Physiology and pathophysiology of iron cardiomyopathy in thalassemia.

    Science.gov (United States)

    Wood, John C; Enriquez, Cathleen; Ghugre, Nilesh; Otto-Duessel, Maya; Aguilar, Michelle; Nelson, Marvin D; Moats, Rex; Coates, Thomas D

    2005-01-01

    Iron cardiomyopathy remains the leading cause of death in patients with thalassemia major. Magnetic resonance imaging (MRI) is ideally suited for monitoring thalassemia patients because it can detect cardiac and liver iron burdens as well as accurately measure left ventricular dimensions and function. However, patients with thalassemia have unique physiology that alters their normative data. In this article, we review the physiology and pathophysiology of thalassemic heart disease as well as the use of MRI to monitor it. Despite regular transfusions, thalassemia major patients have larger ventricular volumes, higher cardiac outputs, and lower total vascular resistances than published data for healthy control subjects; these hemodynamic findings are consistent with chronic anemia. Cardiac iron overload increases the relative risk of further dilation, arrhythmias, and decreased systolic function. However, many patients are asymptomatic despite heavy cardiac burdens. We explore possible mechanisms behind cardiac iron-function relationships and relate these mechanisms to clinical observations.

  14. Role of thalassemia screening in prevention and control of thalassemia - a 5 year experience

    Directory of Open Access Journals (Sweden)

    Suman Lata Mendiratta

    2016-09-01

    Conclusions: Lack of awareness, late registration, husbands not coming/turning up for their test and and ldquo;at risk couples and rdquo; opting out of prenatal diagnosis are the cause of thalassemia major births which can be prevented if awareness is generated amongst masses, screening and prenatal genetic diagnosis services are made widely available. [Int J Reprod Contracept Obstet Gynecol 2016; 5(9.000: 3107-3111

  15. The beta-globin gene in Sardinian delta beta 0-thalassemia carries a C----T nonsense mutation at codon 39.

    OpenAIRE

    Guida, S; Giglioni, B; Comi, P; Ottolenghi, S; Camaschella, C.; Saglio, G

    1984-01-01

    Sardinian delta beta 0-thalassemia is an inherited syndrome characterized by the inactivity of the beta-globin gene and the persistent activity of the fetal gamma-globin genes, particularly the A gamma-globin gene. Previous mapping studies with restriction enzymes failed to show any abnormality in the non-alpha globin gene cluster. We have now examined the possibility that this syndrome might result from a single rather than two different defects. Restriction enzyme polymorphisms linked to th...

  16. Polar Cap Patch Dynamics

    Science.gov (United States)

    2013-04-25

    cap arcs Citation: Hosokawa, K., J. I. Moen, K. Shiokawa, and Y. Otsuka ( 2011 ), Motion of polar cap arcs , J. Geophys. Res. , 116 , A01305, doi...K., J. I. Moen, K. Shiokawa, and Y. Otsuka , (2011), Decay of polar cap patch, J. Geophys. Res., 116, A05308, doi:10.1029/2010JA016287, Abstract. We

  17. Serum Lipids in Turkish Patients with β-Thalassemia Major and β-Thalassemia Minor

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    Yasemin Işık Balcı

    2016-03-01

    Full Text Available It is well-known that β-thalassemia is associated with changes in plasma lipids and lipoproteins [1,2,3]. To our knowledge, no data are available on lipid profiles in Turkish β-thalassemia major (TM and β-thalassemia trait (TT patients together. The aim of this study was to evaluate lipid profiles in two groups of patients with β-TM and β-TT and to compare them with healthy controls. The study included a total of 311 subjects. Group 1 included 131 β-TM patients (mean age: 16.3±7.58 years. Group 2 included 68 β-TT patients (mean age: 7.25±4.43 years. Group 3 consisted of 112 age- and sex-matched healthy controls (mean age: 9±4.7 years. Serum ferritin level was 2487±1103 (range: 661-5745 ng/mL in Group 1. In comparing the correlation between ferritin and lipid parameters, while a significantly negative relationship was detected between ferritin and highdensity lipoprotein cholesterol (HDL-C (p=0.000, r=-0.602, a significantly positive relationship was detected between ferritin and triglyceride (TG levels (p=0.02 in TM patients. Serum lipid profiles of the 3 groups are shown in Table 1.

  18. Study of ocular manifestations in children of thalassemia

    OpenAIRE

    Dhara K. Gosai; K. M. Mehariya; Jigarkumar B. Gosai

    2014-01-01

    Background: Purpose of current study was to study the ocular manifestations in beta-thalassemia major patients and assess the ocular side-effects of iron chelating agents. Methods: Cross sectional study included 45 beta Thalassemia major patients from age group of 6months to 12 years were taken. Full medical history, thorough physical examinations were done to all patients groups, and ophthalmological examination to determine the prevalence of ocular manifestations for all patient groups a...

  19. Laboratory on thalassemia which is a public health problem

    OpenAIRE

    2014-01-01

    Thalassemia which is also known as Mediterranean Anemia, is the most commonly observed hereditary blood disease in our country and in the world. This disease group which shows autosomal recessive transmission is a heterogeneous one group of disease which is characterized with hypochromic microcytic anemia that develops in the result of inherited defect of one or more of the hemoglobin chains. Thalassemia occurs either when hemoglobin chain or chains which are described as α,β,γ...

  20. Diabetes mellitus in β-thalassemia major patients

    Directory of Open Access Journals (Sweden)

    Riadi Wirawan

    2003-06-01

    Full Text Available β-thalassemia major is a disease caused by β polypeptide chain synthesis disorder which is inherited as an autosomal recessive from both parents which is marked by little or no β globin chain synthesis. Medication for β thalassemia major patients is by repeated blood transfusions, which causes hemochromatosis. Hemochromatosis can occur in various organs including the pancreas. The aim of the study was to assess the alteration of plasma glucose concentration and the hemochromatosis prevalence. Fasting plasma glucose concentration and serum ferritin examination were measured in 115 β thalassemia major patients with ages between 10-23 years who were out-patients in the Thalassemia Centre, Department of Child Health, Medical School, University of Indonesia / Dr. Cipto Mangunkusumo General Hospital, Jakarta. The plasma glucose concentration examination was conducted by the GDH enzymatic method, with American Diabetes Association (ADA criteria in the evaluation, while the serum ferritin examination was conducted with the microparticle enzyme immuno assay (MEIA method. All patients had hemochromatosis, 14.8% of the patients had impaired fasting glucose level and 2.6% of the patients showed indications of diabetes mellitus. β thalassemia major patients who receive frequent transfusions will develop hemochromatosis that will in turn impair the pancreatic function. (Med J Indones 2003; 12: 87-93 Keywords : β thalassemia major, hemochromatosis, diabetes mellitus

  1. Prevalence of hepatosplenomegaly in beta thalassemia minor subjects in Iran

    Energy Technology Data Exchange (ETDEWEB)

    Karimi, Mehran [Hemostasis and Thrombosis Unit, Hematology Research Center, school of Medicine, Shiraz University of medical sciences, Shiraz (Iran, Islamic Republic of)], E-mail: Karimim@sums.ac.ir; Bagheri, Mohammad Hadi [Department of Radiology, School of Medicine, Shiraz University of Medical Sciences, Shiraz (Iran, Islamic Republic of); Tahmtan, Mehdi [Hemostasis and Thrombosis Unit, Hematology Research Center, school of Medicine, Shiraz University of medical sciences, Shiraz (Iran, Islamic Republic of); Shakibafard, Alireza [Department of Radiology, School of Medicine, Shiraz University of Medical Sciences, Shiraz (Iran, Islamic Republic of); Rashid, Murtaza [Hemostasis and Thrombosis Unit, Hematology Research Center, school of Medicine, Shiraz University of medical sciences, Shiraz (Iran, Islamic Republic of)

    2009-01-15

    Introduction: Thalassemia is the most common hereditary blood disorder in the world. Iran is located on the thalassemic belt and there is a high prevalence of the hepatosplenomegaly in beta thalassemia minor patients which is reported to be very variable. The goal of this research was to study the frequency of these signs in the cases with beta thalassemia minor patients in Iran. Materials and methods: Two hundred and fifty-nine cases that referred to center for pre-marriage tests were divided into two groups according to their MCV, MCH, and HbA2 (beta thalassemia minor cases and control groups). Liver and spleen sizes were determined by ultrasonographic method and the two groups were compared with each other. Results: Average spleen volumes in case and control groups were 163.48 {+-} 133.97 and 126.29 {+-} 53.98 mm{sup 3}, respectively. Average spleen lengths in case and control groups were 10.71 {+-} 1.52 and 10.60 {+-} 5.4 cm, respectively. Conclusion: In the regions with high frequency of beta thalassemia, in case of finding large spleen size in the ultrasonography, a probable harmless differential diagnosis will be beta thalassemia minor that is not indicative of any serious disease. Volumetric measurement of spleen is more reliable for detection of splenomegaly in these patients.

  2. Recent trends in the gene therapy of β-thalassemia.

    Science.gov (United States)

    Finotti, Alessia; Breda, Laura; Lederer, Carsten W; Bianchi, Nicoletta; Zuccato, Cristina; Kleanthous, Marina; Rivella, Stefano; Gambari, Roberto

    2015-01-01

    The β-thalassemias are a group of hereditary hematological diseases caused by over 300 mutations of the adult β-globin gene. Together with sickle cell anemia, thalassemia syndromes are among the most impactful diseases in developing countries, in which the lack of genetic counseling and prenatal diagnosis have contributed to the maintenance of a very high frequency of these genetic diseases in the population. Gene therapy for β-thalassemia has recently seen steadily accelerating progress and has reached a crossroads in its development. Presently, data from past and ongoing clinical trials guide the design of further clinical and preclinical studies based on gene augmentation, while fundamental insights into globin switching and new technology developments have inspired the investigation of novel gene-therapy approaches. Moreover, human erythropoietic stem cells from β-thalassemia patients have been the cellular targets of choice to date whereas future gene-therapy studies might increasingly draw on induced pluripotent stem cells. Herein, we summarize the most significant developments in β-thalassemia gene therapy over the last decade, with a strong emphasis on the most recent findings, for β-thalassemia model systems; for β-, γ-, and anti-sickling β-globin gene addition and combinatorial approaches including the latest results of clinical trials; and for novel approaches, such as transgene-mediated activation of γ-globin and genome editing using designer nucleases.

  3. Altered erythropoiesis and iron metabolism in carriers of thalassemia.

    Science.gov (United States)

    Guimarães, Jacqueline S; Cominal, Juçara G; Silva-Pinto, Ana Cristina; Olbina, Gordana; Ginzburg, Yelena Z; Nandi, Vijay; Westerman, Mark; Rivella, Stefano; de Souza, Ana Maria

    2015-06-01

    The thalassemia syndromes (α- and β-thalassemia) are the most common and frequent disorders associated with ineffective erythropoiesis. Imbalance of α- or β-globin chain production results in impaired red blood cell synthesis, anemia, and more erythroid progenitors in the blood stream. While patients affected by these disorders show definitive altered parameters related to erythropoiesis, the relationship between the degree of anemia, altered erythropoiesis, and dysfunctional iron metabolism has not been investigated in both α-thalassemia carriers (ATC) and β-thalassemia carriers (BTC). Here, we demonstrate that ATC have a significantly reduced hepcidin and increased soluble transferrin receptor levels but relatively normal hematological findings. In contrast, BTC have several hematological parameters significantly different from controls, including increased soluble transferrin receptor and erythropoietin levels. These changes in both groups suggest an altered balance between erythropoiesis and iron metabolism. The index sTfR/log ferritin and (hepcidin/ferritin)/sTfR are, respectively, increased and reduced relative to controls, proportional to the severity of each thalassemia group. In conclusion, we showed in this study, for the first time in the literature, that thalassemia carriers have altered iron metabolism and erythropoiesis.

  4. The Prevalence of Thalassemia Minor in The Aliabad Katool

    Directory of Open Access Journals (Sweden)

    F Niknezhad

    2007-01-01

    Full Text Available Background & Objectives: Thalassemia syndromes isone of the inherited disorders in which one or more globulin chains are affected. On the basis of clinical symptoms, thalassemias are categorized as minor, intermediate, and major. Minor beta -thalassemia is a mild microcytic hypo chromic anemia; in most cases asymptomatic and HbA2 is more than normal. Materials & Methods: This study carried out on 813 blood samples obtained from male high school students of Aliabad Katool, in the north of Iran. After detecting red blood cell indices of the subjects whose MCV was less than 80fl HbA study performed. Results: The MCV of 8.24% of the subjects was less than 80fl.34 of 67 had HbA2 of less than 3.5 %(normal while the rest more than 3.5%(minor. Conclusions: Since about 50% of microcytic anemic patients were the carrier of beta-thalassemia and it is highly Prevalent in this region (4.06%, we recommend to investigate HbA2 in people with MCV less than 80 fl. Keyword: Thalassemia, Thalassemia minor, HbA2, Iran

  5. Pain in thalassemia - an emerging complication

    Directory of Open Access Journals (Sweden)

    P.J. Giardina

    2011-12-01

    Full Text Available Many thalassemia subjects both transfused Major (TM and nontransfused Intermedia (TI suffer from longstanding bone disease, reduced or low bone mass (osteopenia or osteoporosis, fractures and bone pain. Unexpected musculoskeletal disease occurs despite longstanding hypertransfusion and new iron chelation strategies. Conditions which have been implicated in its pathogenesis include the massive ineffective erythropoiesis, chronic hypoxia associated with anemia, the local metabolic dysfunction from hemochromatosis, iron chelation toxicity, trace mineral deficiencies such as zinc deficiency, low vitamin D concentrations, the effect of endocrine dysfunction such as hypoparathyroidism, hypogonadism and growth hormone deficiency from hemochromatosis and the chronic inflammatory state induced by iron excess. The pathogenesis of bone disease has been attributed to the underlying marrow expansion of medullary bone caused by the massive ineffective erythropoiesis and subsequent cortical thinning. The process of normal bone health is maintained by a metabolic interplay of several hormonal factors including growth hormone, estrogen, testosterone, parathyroid hormone all of which can be diminished by iron overload in Thalassemia. Trace metals and vitamins including calcium, copper, zinc or vitamin C can also be deficient from iron excess or iron chelation which are also important contributors to bone metabolism. Indeed toxicities of iron chelation itself on bone development in the growing child associated with zinc deficiency, high Deferoxamine dosing and low iron burdens or the collagenous joint disease associated with deferiprone chelation have further contributed to the current musculoskeletal disease of Thalassemias. Decreased spinal height, vertebral flattening and scoliosis have also been reported. Magnetic Resonance Imaging (MRI of adolescent and adult β Thalassemia Major and Intermedia patients with osteoporosis and pain have assisted in defining the

  6. Genotype and phenotype characterizations in a large cohort of β-thalassemia heterozygote with different forms of α-thalassemia in northeast Thailand.

    Science.gov (United States)

    Yamsri, Supawadee; Sanchaisuriya, Kanokwan; Fucharoen, Goonnapa; Sae-Ung, Nattaya; Fucharoen, Supan

    2011-08-15

    In order to update the molecular basis of β-thalassemia and describe hematological features among different mutations and the concurrent of α- and β-thalassemias, 849 unrelated β-thalassemia heterozygotes recruited in northeast Thailand during a prevention and control program were studied. β- and α-thalassemia mutations were investigated using the polymerase chain reaction (PCR)-based technologies and hematological parameters were recorded using standard methods. Seventeen different mutations including both β(0)- and β(+) -thalassemias were identified. Eight of these 17 β-thalassemia alleles accounted for 97.4%, others were found at lower frequencies (<1.0%). Of the 849 cases, 626 were investigated for common α-thalassemia mutations and 155 (24.8%) were found to be co-inherited with different forms of α-thalassemia. Comparison of the hematological parameters among different β-thalassemia mutations revealed an increasing trend of MCV and MCH in a group of heterozygous states for the 3.4kb deletion and the A-G substitution at nucleotide (NT) -28. Hb A(2) and Hb F levels in individuals with the 3.4kb deletion were significantly higher than those with other mutations. Interaction of each β-thalassemia mutation with α-thalassemia did not affect the diagnostic ranges of Hb A(2) and Hb F, though the significantly increased MCV and MCH was noted. These findings underline the heterogeneity of β-thalassemia and the importance of hematological and molecular analyses of both α-and β-thalassemias in the diagnosis and genetic counseling of the couples at-risk of having babies with severe thalassemia diseases in the region.

  7. Reduced risk of uncomplicated malaria episodes in children with a+-thalassemia in northeastern Tanzania

    DEFF Research Database (Denmark)

    Enevold, Anders; Lusingu, John P; Mmbando, Bruno

    2008-01-01

    the susceptibility to uncomplicated malaria. We compared the risk of suffering from febrile, uncomplicated malaria between individuals carrying three common RBC polymorphisms (sickle cell trait, alpha(+)-thalassemia, and glucose-6-phosphate-dehydrogenase deficiency) and controls. The study was performed in an area......The prevalence of human red blood cell (RBC) polymorphisms is high in areas of intense Plasmodium falciparum transmission, and individuals carrying these genetic traits are believed to be partially protected against severe malaria. However, it remains uncertain how RBC polymorphisms affect...

  8. Oxidative stress and antioxidant status in beta-thalassemia heterozygotes

    Directory of Open Access Journals (Sweden)

    Luciana de Souza Ondei

    2013-01-01

    Full Text Available Background: Several studies have evaluated the oxidant and antioxidant status of thalassemia patients but most focused mainly on the severe and intermediate states of the disease. Moreover, the oxidative status has not been evaluated for the different beta-thalassemia mutations. Objective: To evaluate lipid peroxidation and Trolox equivalent antioxidant capacity in relation to serum iron and ferritin in beta thalassemia resulting from two different mutations (CD39 and IVS-I-110 compared to individuals without beta-thalassemia. Methods: One hundred and thirty subjects were studied, including 49 who were heterozygous for beta-thalassemia and 81 controls. Blood samples were subjected to screening tests for hemoglobin. Allele-specific polymerase chain reaction was used to confirm mutations for beta-thalassemia, an analysis of thiobarbituric acid reactive species was used to determine lipid peroxidation, and Trolox equivalent antioxidant capacity evaluations were performed. The heterozygous beta-thalassemia group was also evaluated for serum iron and ferritin status. Results: Thiobarbituric acid reactive species (486.24 ± 119.64 ng/mL and Trolox equivalent antioxidant capacity values (2.23 ± 0.11 mM/L were higher in beta-thalassemia heterozygotes compared to controls (260.86 ± 92.40 ng/mL and 2.12 ± 0.10 mM/L, respectively; p-value < 0.01. Increased thiobarbituric acid reactive species values were observed in subjects with the CD39 mutation compared with those with the IVS-I-110 mutation (529.94 ± 115.60 ng/mL and 453.39 ± 121.10 ng/mL, respectively; p-value = 0.04. However, average Trolox equivalent antioxidant capacity values were similar for both mutations (2.20 ± 0.08 mM/L and 2.23 ± 0.12 mM/L, respectively; p-value = 0.39. There was no influence of serum iron and ferritin levels on thiobarbituric acid reactive species and Trolox equivalent antioxidant capacity values. Conclusion: This study shows an increase of oxidative stress and

  9. Sickle cell syndrome. Association between hemoglobin S and β thalassemia

    Directory of Open Access Journals (Sweden)

    Nehuen P. Gasparini

    2016-12-01

    Full Text Available Sickle cell syndrome HbS/β thalassemia is an inheritable mendelian type disease where two affected alleles are simultaneously present, one from HbS (βS and the other from β thalassemia. That situation is mainly linked to individuals who share African and Mediterranean ancestors. The mutation responsible for HbS is a point mutation, whereas for β thalassemia, there are more than 200 mutations that cause different degrees of deficiency synthesis of β globin chain, which justifies the clinical and genetic heterogeneity of this syndrome. It is presented a clinical case of a young adult man with limited resources that consulted by longstanding bone pain. The patient presented anemia with a marked microcytosis. Hemoglobin electrophoresis was performed, an abnormal peak in position of HbS and high HbA2 fraction were detected. These last results indicated two possible molecular alterations simultaneously, for this reason the molecular study was performed looking for the most common β thalassemia mutations in our population and, the point mutation responsible for S hemoglobinopathy. Clinical data and biochemical laboratory allowed the diagnosis of sickle cell syndrome. The molecular study confirmed the syndrome carrying mutations IVS-I nt 110 G > A, responsible for β thalassemia and, codon 6 A > T (GAG → GTG: Glu → Val responsible for S hemoglobinophaty. Since it is a disease of high health impact, it is important to provide genetic counseling to the whole family.

  10. Thalassemia and hemoglobinopathies in Thua Thien Hue Province, Central Vietnam.

    Science.gov (United States)

    Nguyen, Hoa Van; Sanchaisuriya, Kanokwan; Nguyen, Dung; Phan, Hoa Thi Thuy; Siridamrongvattana, Sirivara; Sanchaisuriya, Pattara; Fucharoen, Supan; Fucharoen, Goonnapa; Schelp, Frank P

    2013-01-01

    A community-based assessment of thalassemias and hemoglobinopathies was conducted at the Thua Thien Hue Province, Central Vietnam. By cluster sampling, a total of 410 pregnant women attending the antenatal care service at 30 commune health centers were recruited consecutively from September 2011 to June 2012. Hemoglobin (Hb) analysis was performed using an automated Hb analyzer. α-Thalassemia (α-thal) genes were identified by polymerase chain reaction (PCR)-based techniques. Out of the 410 pregnant women, 2.7% carried α(0)-thal and 1.2% were β-thal carriers. One woman with the - -(THAI) deletion was also found. Among the females under survey, structural Hb variants with 3.2% Hb E [β26(B8)Glu→Lys, GAG>AAG; HBB: c.78G>C] and 3.7% Hb Constant Spring [Hb CS; α142, Term→Gln, TAA>CAA (α2); HBA2: c.427T>C] were found. Assessing the frequency of thalassemias and hemoglobinopathies by ethnicity, Kinh (Vietnamese) and ethnic minority groups, Hb CS with a high frequency of 24.0% was observed in the ethnic minority groups. These results provide basic population-based information, are useful not only for implementing measures for prevention and control of thalassemias in the region but also for studying the importance of thalassemias and hemoglobinopathies in ethnic minorities within Southeast Asia.

  11. Prevalence of Pulmonary Hypertension in Patients with Thalassemia Intermedia in 2009: a single center’s experience

    OpenAIRE

    2015-01-01

    Background: There are various clinical symptoms of thalassemia intermedia, and they lie roughly between those of major and minor forms of the disease. Patients with thalassemia intermedia occasionally require blood transfusions. This renders them susceptible to pulmonary arterial hypertension (PAH) syndrome, which is one of the most significant complications in patients with thalassemia intermedia. PAH is more common in in thalassemia intermedia than in thalassemia major, and it may cause car...

  12. Microtubule's conformational cap

    DEFF Research Database (Denmark)

    Chretien, D.; Janosi, I.; Taveau, J.C.

    1999-01-01

    The molecular mechanisms that allow elongation of the unstable microtubule lattice remain unclear. It is usually thought that the GDP-liganded tubulin lattice is capped by a small layer of GTP- or GDP-P(i)-liganded molecules, the so called "GTP-cap". Here, we point-out that the elastic properties...

  13. 广西贵港地区地中海贫血高风险人群的发病率及基因检测%Incidence and genetic test of thalassemia among high-risk population in Guigang City

    Institute of Scientific and Technical Information of China (English)

    李燕; 吴汉锋; 钟伟明

    2012-01-01

    Objective To analyze the incidence and genetic distribution of thalassemia among high-risk population in Guigang City of Guangxi Province,and provide the basis for the prevention the born of severe babies with thalassemia. Methods Among 342 high-risk people with thalassemia from January 2011 to June 2011, a detection gene were detected with gap-PCR,and RDB were applied for the detection of three alpha thalassemia point mutations and 17 kinds of beta thalassemia. Results The total detection rate was 80.99% with 167 alpha thalassemia cases, 101 beta Mediterranean anemia cases,9 double heterozygous cases. Conclusion Thalassemia is highly prevalent in Guangxi,therefore,genetic detection can enhance the detection rate of thalassemia and it is essentially conducive to giving sound child birth and reducing the birth of thalsssemia child.%目的 研究广西贵港地区地中海贫血高风险人群的发病率及基因分布,为预防地中海贫血重症患儿的出生、减少出生缺陷及提高人口素质服务.方法 2011年1月~2011年6月期间,对具有地中海贫血高风险的342人,应用单管多重PCR技术进行α缺失型基因检测以及反向点杂交法检测中国人常见的三种α-地中海贫血点突变和中国人常见的17种β-地中海贫血.结果 342人中检出α-地中海贫血167例,β-地中海贫血101例,α和β地贫双重杂合子9例,检出率为80.99%.结论 广西是地中海贫血高发区,应用基因诊断,有效地提高地中海贫血的检出率,对优生优育、干预重症地贫儿出生有着重要作用.

  14. Hepcidin and Hfe in iron overload in beta-thalassemia.

    Science.gov (United States)

    Gardenghi, Sara; Ramos, Pedro; Follenzi, Antonia; Rao, Niva; Rachmilewitz, Eliezer A; Giardina, Patricia J; Grady, Robert W; Rivella, Stefano

    2010-08-01

    Hepcidin (HAMP) negatively regulates iron absorption, degrading the iron exporter ferroportin at the level of enterocytes and macrophages. We showed that mice with beta-thalassemia intermedia (th3/+) have increased anemia and iron overload. However, their hepcidin expression is relatively low compared to their iron burden. We also showed that the iron metabolism gene Hfe is down-regulated in concert with hepcidin in th3/+ mice. These observations suggest that low hepcidin levels are responsible for abnormal iron absorption in thalassemic mice and that down-regulation of Hfe might be involved in the pathway that controls hepcidin synthesis in beta-thalassemia. Therefore, these studies suggest that increasing hepcidin and/or Hfe expression could be a strategy to reduces iron overload in these animals. The goal of this paper is to review recent findings that correlate hepcidin, Hfe, and iron metabolism in beta-thalassemia and to discuss potential novel therapeutic approaches based on these recent discoveries.

  15. Hepcidin and Hfe in iron overload in β-thalassemia

    Science.gov (United States)

    Gardenghi, Sara; Ramos, Pedro; Follenzi, Antonia; Rao, Niva; Rachmilewitz, Eliezer A.; Giardina, Patricia J.; Grady, Robert W.; Rivella, Stefano

    2013-01-01

    Hepcidin (HAMP) negatively regulates iron absorption, degrading the iron exporter ferroportin at the level of enterocytes and macrophages. We showed that mice with β-thalassemia intermedia (th3/+) have increased anemia and iron overload. However, their hepcidin expression is relatively low compared to their iron burden. We also showed that the iron metabolism gene Hfe is down-regulated in concert with hepcidin in th3/+ mice. These observations suggest that low hepcidin levels are responsible for abnormal iron absorption in thalassemic mice and that down-regulation of Hfe might be involved in the pathway that controls hepcidin synthesis in β-thalassemia. Therefore, these studies suggest that increasing hepcidin and/or Hfe expression could be a strategy to reduces iron overload in these animals. The goal of this paper is to review recent findings that correlate hepcidin, Hfe, and iron metabolism in β-thalassemia and to discuss potential novel therapeutic approaches based on these recent discoveries. PMID:20712796

  16. Autoimmune hemolytic anemia in patients with β-thalassemia major.

    Science.gov (United States)

    Xu, Lu-Hong; Fang, Jian-Pei; Weng, Wen-Jun; Huang, Ke; Zhang, Ya-Ting

    2012-04-01

    Hemolysis is a common feature in patients with β-thalassemia major. As a result, autoimmune hemolytic anemia complicating β-thalassemia is easily overlooked. Here, the authors described the clinical features and management of 7 patients with β-thalassemia major and autoimmune hemolytic anemia. These patients had fever, cough, and tea-colored urine on admission. The laboratory investigations showed a significant drop in hemoglobin and increased serum bilirubin. Coombs' tests revealed that anti-immunoglobulin G (IgG) and anti-C3 was positive in 7 and 5 cases, respectively, whereas anti-Rh E alloantibody was positive in 3 cases. All the patients received corticosteroids treatments and blood transfusions. Patients with anti-Rh E alloantibodies also received immunoglobulin treatments. Six of the patients responded well to the management, but 1 patient developed recurrent autoimmune hemolytic anemia that required cyclosporin A treatment. All the patients remained well by following up for more than 6 months.

  17. 孕妇地中海贫血的产前筛选与诊断%Prenatal screen and diagnosis of thalassemia.

    Institute of Scientific and Technical Information of China (English)

    卢巧云; 徐婉芳

    2011-01-01

    目的 总结在我院进行产前体检者中开展地中海贫血的产前筛选与诊断结果.研究运用血红蛋白分析法进行孕妇产前筛选与诊断的意义.方法 对2 219对夫妇使用血红蛋白定量法结合基因分析,进行常规地中海贫血筛选.从中筛选出双方同为地中海贫血基因携带者的夫妇,建议其进行相关的产前诊断.对同意进行产前诊断的孕早期孕妇,采取其羊水或绒毛样本进行地中海贫血基因诊断;对同意进行产前诊断的孕中晚期孕妇,以B超下穿刺法抽取脐静脉血样进行地中海贫血基因诊断.结果 检查出夫妇一方为轻度α-地中海贫血基因携带者221例,检出率为4.98%;检查出夫妇一方为轻度β-地中海贫血基因携带者133例,检出率为3.00%.检查出双方均为地中海贫血基因携带者共13对,其中同意进行产前诊断的11例,诊断为中、重型地中海贫血胎儿5例.结论 开展孕妇地中海盆血的产前筛选与诊断,可尽早确诊中、重型地中海贫血胎儿,为家庭和社会减轻了负担与痛苦.%Objective To analyze the results of prenatal screen and diagnosis of thalassemia in 4438 pregnant women. Methods Quantitation of hemoglobin and thalassemia genetic analysis were used for screening thalassemia in 2219 couples. The couples carring thalassemia genes were suggested to take some related prenatal examinations. After permission, amniotic fluid or chorionic villi samples, and umbilical vein blood were collected from early and middle - late gestation respectively for the detection of thalassemia gene. Results Mild alpha - thalassemia gene carrier and mild beta - thalassemia gene carrier in one person of the couple were found in 221 cases ( 4.98% ) and 133 cases ( 3.00% ) respectively;thalassemia gene was found in both husband and wife in 13 couples. Of the 13 couples, 11 agreed to make prenatal diagnosis and 5 foetus of them were diagnosed as heavy thalassemia. Conclusion

  18. Variable Clinical Phenotypes of α-Thalassemia Syndromes

    Directory of Open Access Journals (Sweden)

    Sylvia Titi Singer

    2009-01-01

    Full Text Available Genetic mutations of the α genes are common worldwide. In Asia and particularly Southeast Asia, they can result in clinically significant types of α-thalassemia, namely hemoglobin (Hb H disease and Hb Bart's hydrops fetalis. The latter is generally a fatal intrauterine condition, while Hb H disease results in clinical complications that are frequently overlooked. The high prevalence of the carrier state and the burden of these diseases (and other α-thalassemia variants call for more attention for improved screening methods and better care.

  19. [RDBH-method and big DyeTM terminator technology in accurate diagnosis of β-thalassemia and the allelic polymorphism of β-globin cluster].

    Science.gov (United States)

    Akperova, G A

    2014-11-01

    IThe purpose of this study was to evaluate of the efficiency of RDBH-method and Big DyeTM Terminator technology in an accurate diagnosis of β-thalassemia and the allelic polymorphism of β-globin cluster. It was done a complete hematology analysis (HB, MCH, MCV, MCHC, RBC, Hct, HbA2, HbF, Serum iron, Serum ferritin at four children (males, 6-10 years old) and their parents. Molecular analysis included Reverse Dot-Blot Hybridization StripAssay (RDBH) and DNA sequencing on ABI PRISM Big DyeTM Terminator. Hematologic and molecular parameters were contradictory. The homozygosity for β0-thalassemia (β0IVS2.1[G>A] and β0codon 8[-AA]) at three boys with the mild clinical manifestation and heterozygosity of their parents for mutations, and the absence of β-globin mutations at parents and a boy who holds monthly transfusion was established by RDBH-analysis. DNA sequencing by technology Big DyeTM Terminator showed polymorphism at positions -551 and -521 of Cap5'-region (-650-250) - (AT)7(T)7 and (AT)8(T)5. Application of the integrated clinical-molecular approach is an ideal method for an accurate diagnosis, identification of asymptomatic carriers and a reduce of the risk of complications from β-thalassemia, moreover screening of γG-gene and the level of fetal hemoglobin in early childhood will help manage of β-thalassemia clinic and prevent heavy consequences of the disease.

  20. 地中海贫血基因诊断在优生优育中的应用%Application of the eugenics in the gene diagnosis of thalassemia

    Institute of Scientific and Technical Information of China (English)

    王志剑; 邓之敏; 邝永辉

    2014-01-01

    目的:探讨河源地区地中海贫血的发病情况及基因分型。为开展地中海贫血的遗传咨询、产前诊断和预防计划提供参考。方法用一管定量法红细胞渗透脆性检测筛检受检人员,对筛查阳性或阴性临床疑似病例及部分贫血查因病例进行地贫基因检测。结果在7872例受检者,筛查出阳性272例,发生率为3.5%;对筛查部分阳性和阴性临床疑似病例及部分贫血查因病例标本132例进行地中海贫血基因检测,其中α地中海贫血48例(36.4%),β地中海贫血45例(34.1%),α、β混合型地中海贫血6例(4.5%),非地中海贫血33例(25%)。基因诊断为地中海贫血患者中(99例)筛查为阴性者19例,漏诊率为19.1%结论河源地区人口中的α与β地中海贫血的基因突变类型和频率较高,婚前检查、孕检或产前诊断应以地中海贫血基因诊断为主,为遗传咨询提供了理论依据,减少本地区地中海贫血的发生率。%Objective The incidence of thalassemia in Heyuan and studying gene typing. To provide reference for genetic counseling, prenatal diagnosis of Mediterranean anemia and prevention program. Methods Using a quantita-tive method erythrocyte osmotic fragility test screening inspection personnel, to screen the positive or negative clinical sus-pected cases and anemia were thalassemia gene detection check. Results in 7 872 examined cases, screening out the positive in 272 cases, the positive rate was 3.5%; Screening for part of the positive and negative clinical suspected cases and anemia check cases specimens from 132 patients were thalassemia gene detection, including 48 cases of alpha tha-lassemia (36.4%), 45 patients with beta thalassemia (34.1%), 6 cases of alpha, beta thalassemia mixed type (4.5%), 33 cas-es (25%) of non thalassemia. gene diagnosis for thalassemia patients (99 cases) screening was negative in 19 cases, the missed diagnosis rate was 19

  1. Clinical, hematologic and molecular variability of sickle cell-β thalassemia in western India

    Directory of Open Access Journals (Sweden)

    Mukherjee Malay

    2010-01-01

    Full Text Available Background: Sickle cell-β thalassemia (HbS-β thalassemia is a sickling disorder of varying severity, which results from compound heterozygosity for sickle cell trait and β thalassemia trait. The present study was undertaken to determine the genetic factors responsible for the clinical variability of HbS-β thalassemia patients from western India. Materials and Methods: Twenty-one HbS-β thalassemia cases with variable clinical manifestations were investigated. The α and β globin gene clusters were studied by molecular analysis. Results: Thirteen patients showed milder clinical presentation as against eight patients who had severe clinical manifestations. Four β thalassemia mutations were identified: IVS 1-5 (G→C, codon 15 (G→A, codon 30 (G→C and codon 8/9 (+G. α thalassemia and XmnI polymorphism in homozygous condition (+/+ were found to be common among the milder cases. The βS chromosomes were linked to the typical Arab-Indian haplotype (#31. Framework (FW linkage studies showed that four β thalassemia mutations were associated with different β globin gene frameworks. Linkage of codon 15 (G→A mutation to FW2 is being observed for the first time. Conclusion: The phenotypic expression of HbS-β thalassemia is not uniformly mild and α thalassemia and XmnI polymorphism in homozygous condition (+/+ are additional genetic factors modulating the severity of the disease in the Indian subcontinent.

  2. Cradle Cap (For Parents)

    Science.gov (United States)

    ... is the common term for seborrheic dermatitis , or seborrhea, which is called dandruff in older kids and ... another factor in the development of cradle cap. Seborrhea happens most often in babies and teenagers. In ...

  3. alpha-Globin genes: thalassemic and structural alterations in a Brazilian population

    Directory of Open Access Journals (Sweden)

    M.R.S.C. Wenning

    2000-09-01

    Full Text Available Seven unrelated patients with hemoglobin (Hb H disease and 27 individuals with alpha-chain structural alterations were studied to identify the alpha-globin gene mutations present in the population of Southeast Brazil. The -alpha3.7, --MED and -(alpha20.5 deletions were investigated by PCR, whereas non-deletional alpha-thalassemia (alphaHphalpha, alphaNcoIalpha, aaNcoI, alphaIcalpha and alphaTSaudialpha was screened with restriction enzymes and by nested PCR. Structural alterations were identified by direct DNA sequencing. Of the seven patients with Hb H disease, all of Italian descent, two had the -(alpha20.5/-alpha3.7 genotype, one had the --MED/-alpha3.7 genotype, one had the --MED/alphaHphalpha genotype and three showed interaction of the -alpha3.7 deletion with an unusual, unidentified form of non-deletional alpha-thalassemia [-alpha3.7/(aaT]. Among the 27 patients with structural alterations, 15 (of Italian descent had Hb Hasharon (alpha47Asp->His associated with the -alpha3.7 deletion, 4 (of Italian descent were heterozygous for Hb J-Rovigo (alpha53Ala->Asp, 4 (3 Blacks and 1 Caucasian were heterozygous for Hb Stanleyville-II (alpha78Asn->Lys associated with the alpha+-thalassemia, 1 (Black was heterozygous for Hb G-Pest (alpha74Asp->Asn, 1 (Caucasian was heterozygous for Hb Kurosaki (alpha7Lys->Glu, 1 (Caucasian was heterozygous for Hb Westmead (alpha122His->Gln, and 1 (Caucasian was the carrier of a novel silent variant (Hb Campinas, alpha26Ala->Val. Most of the mutations found reflected the Mediterranean and African origins of the population. Hbs G-Pest and Kurosaki, very rare, and Hb Westmead, common in southern China, were initially described in individuals of ethnic origin differing from those of the carriers reported in the present study and are the first cases to be reported in the Brazilian population.

  4. Total Antioxidant Status in Patients with Major β-Thalassemia

    Directory of Open Access Journals (Sweden)

    Lili Koochakzadeh

    2011-06-01

    Full Text Available Objective:Beta-thalassemia major is an autosomal recessive disease causing severe and hemolytic anemia, which begins about 2-6 months after birth. Iron overload, which arises from recurrent transfusion and ineffective erythropoiesis, can enhance oxidative stress in thalassemic patients. The aim of this study was to evaluate the serum total antioxidant capacity of patients with ß-Thalassemia major. Methods:Sixty six Iranian patients with β-thalassemia major and 66 age-gender matched controls were evaluated for serum total antioxidant status (TAS, uric acid (UA, bilirubin and albumin. In addition, serum ferritin and transaminases were recorded in these subjects. Findings: Significant increases of TAS, UA, and bilirubin were observed in the patient group, compared with the control group (P<0.01. Mean TAS and bilirubin in male patients was higher than in females (P=0.005 and P=0.008, respectively. There was also direct correlation between TAS and albumin (P<0.001, bilirubin (P<0.001 and UA (P=0.002. Conclusion: Endogenous antioxidants such as ferritin, UA and bilirubin can result in increased level of TAS in the patients with Beta-thalassemia major. Compensatory excess of TAS to oxidative stress could also be the reason for difference between our findings and previous studies.

  5. Study of glycolytic intermediates in hereditary elliptocytosis with thalassemia

    Directory of Open Access Journals (Sweden)

    Pavri Roshan

    1977-01-01

    Full Text Available Glycolytic intermediates like ATP, DPG and GSH have been studied in a family with. hereditary elliptocytosis and thalassemia. Results indicate a fall in ATP with a concomitant rise in DPG in the Patient. Findings are discussed in relation to other data.

  6. Relationship between Personality Traits and Happiness in Patients with Thalassemia

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    Babollah Bakhshipour

    2014-12-01

    Full Text Available Background: The aim of this study was determining the relationship between personality traits and happiness in patients with major thalassemia. Materials and Methods: The design of this study was descriptive (correlational study. The target population of this study was all under-treated patients with major thalassemia in Amirkola thalassemia center in 2011. Among these patients, 150 patients were sampled using simple random sampling method and Morgan's table. The data were analyzed by means of calculating Pearson correlation coefficients and multiple linear regression analysis. The patients were asked to complete NEO-five factor Inventory (short form and Oxford happiness inventory. Results: Based on the results, the coefficient of regression analysis of NEO personality factors (big five and happiness was 0.45, which shows a linear relationship between personality factors of NEO and happiness in patients with thalassemia. Thus, there is a statistically significant relationship among personality traits (neuroticism, extroversion, openness, agreeableness, conscientiousness and happiness. Conclusion: Among personality traits, extroversion, flexibility, agreeableness and conscientiousness had positive statistically meaningful relationship with happiness i.e. patients with lower scores in neuroticism, were happier.

  7. The Thalassemia International Federation: a global public health paradigm

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    Elpidoforos S. Soteriades

    2014-09-01

    Full Text Available Many international organizations are struggling today to coordinate limited economic and human resources in support of governments’ efforts to advance public health around the world. The United Nations and the World Health Organization, along with others play a pivotal role in this global effort. Furthermore, during the past few decades an increasingly higher percentage of global efforts on public health are carried out by specific health initiatives, international projects and non-governmental patient-oriented organizations. The Thalassemia International Federation (TIF is one such organization focusing on the control of thalassemia around the world. The current paper aims at presenting a comprehensive overview of the mission, goals, objectives and activities of this organization. Our ultimate goal is to highlight TIF’s public health paradigm and diffuse its success at an international levels for others to follow. TIF is devoted to disseminating information, knowledge, experience and best practices around the world to empower patients with thalassemia and their relatives, support health professionals providing care to such patients and promote national and international policies, which secure equal access to quality care for all patients with thalassemia.

  8. Recent trends in the gene therapy of β-thalassemia

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    Finotti A

    2015-02-01

    Full Text Available Alessia Finotti,1–3 Laura Breda,4 Carsten W Lederer,6,7 Nicoletta Bianchi,1–3 Cristina Zuccato,1–3 Marina Kleanthous,6,7 Stefano Rivella,4,5 Roberto Gambari1–3 1Laboratory for the Development of Gene and Pharmacogenomic Therapy of Thalassaemia, Biotechnology Centre of Ferrara University, Ferrara, Italy; 2Associazione Veneta per la Lotta alla Talassemia, Rovigo, Italy; 3Department of Life Sciences and Biotechnology, Section of Biochemistry and Molecular Biology, Ferrara University, Ferrara, Italy; 4Department of Pediatrics, Division of Haematology/Oncology, Weill Cornell Medical College, New York, NY, USA; 5Department of Cell and Development Biology, Weill Cornell Medical College, New York, NY, USA; 6Department of Molecular Genetics Thalassaemia, The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus; 7Cyprus School of Molecular Medicine, Nicosia, Cyprus Abstract: The β-thalassemias are a group of hereditary hematological diseases caused by over 300 mutations of the adult β-globin gene. Together with sickle cell anemia, thalassemia syndromes are among the most impactful diseases in developing countries, in which the lack of genetic counseling and prenatal diagnosis have contributed to the maintenance of a very high frequency of these genetic diseases in the population. Gene therapy for β-thalassemia has recently seen steadily accelerating progress and has reached a crossroads in its development. Presently, data from past and ongoing clinical trials guide the design of further clinical and preclinical studies based on gene augmentation, while fundamental insights into globin switching and new technology developments have inspired the investigation of novel gene-therapy approaches. Moreover, human erythropoietic stem cells from β-thalassemia patients have been the cellular targets of choice to date whereas future gene-therapy studies might increasingly draw on induced pluripotent stem cells. Herein, we summarize the most

  9. Vitamin E effect on osmotic fragility in β thalassemia major

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    Agus Fitrianto

    2014-09-01

    Full Text Available Background Blood transfusion remains the main therapy for anemia in β thalassemia major patients. However, frequent transfusions can cause oxidative stress in response to iron overload. Vitamin E is considered to be the best lipid-soluble exogenous antioxidant in humans. It can protect phospholipid membrane from peroxidation. Erythrocyte osmotic fragility is a useful test to assess for the improvement of red blood cells in thalassemia patients after vitamin E supplementation. Objective To investigate the effect of vitamin E for improving erythrocyte osmotic fragility in β- thalassemia major and for decreasing the need for frequent transfusions. Methods This was a double blind placebo controlled randomized clinical trial on children aged 2-14 years with thalassemia major who received frequent blood transfusions. Fifty subjects were divided into 2 groups: group I with vitamin E supplementation and group II with placebo, as a control group, for a period of 1 month. Pre- and post-treatment data on erythrocyte osmotic fragility and hemoglobin level were analyzed with non-paired T-test. Results Improved erythrocyte osmotic fragility was found: in group I, pre-treatment 31.59 (SD 6.342% to post-treatment 38.08 (SD 7.165%, compared to the control group pre-treatment 34.40 (SD 6.985% to post-treatment 29.26 (SD 9.011% (P=0.0001. Comparison of the mean delta Hb level in group I was 0.94 (SD 0.605 gr% and that of group II was - 0.23 (SD 1.199 gr% (P= 0.0001. Conclusion Vitamin E supplementation improves erythrocyte fragility and Hb level in β-thalassemia major pediatric patients. [Paediatr Indones. 2014;54:280-3.].

  10. Factors associated with psychiatric disorders that experience individuals with thalassemia

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    Ioannis Koutelekos

    2013-04-01

    Full Text Available Thalassemia is an inherited blood disorder characterized by anomalies in the synthesis of the beta chains of hemoglobin resulting in variable health problems. The chronicity and the nature of the disease impose significant limitations on individuals' life and as a result they frequently experience anxiety and depression. Aim: The aim of the present study was to review the literature about factors associated with psychiatric disorders that experience patients with thalassemia. Method: The method of this study included bibliographic research of the literature from reviews and researches, mainly in the PubMed data base, which referred to the factors associated with psychiatric disorders in patients with thalassaemia. PubMed was searched using the following key search terms: "anxiety", "depression", "thalassaemia" while the research covered the period 1996-2011. Results: Though the developments in the treatment and prognosis of thalassemia have dramatically altered the approach to the care of patients, however the psychological aspects of the disease have received little attention since the number of relevant studies are generally limited. According to the literature, patients with thalassemia frequently experience psychiatric disorders (anxiety and depression due to various reasons, out of which the main are the chronicity of disease, the disease complications, the financial, social and personal problems, the lack of family and social support, the change in body image and the reduction of self-esteem level. Symptoms of anxiety and depression may influence negatively the outcome of the disease including low adherence to treatment, increased morbidity and poor quality of life. Conclusions: A regular screening for anxiety and depression symptoms and identification of individuals at high risk should be an integral part of medical therapy. Early screening implies early treatment and provides valuable information for the planning of intervention programs

  11. The "lively" cytokines network in beta-Thalassemia Major-related osteoporosis.

    Science.gov (United States)

    Morabito, Nunziata; Russo, Giuseppina T; Gaudio, Agostino; Lasco, Antonino; Catalano, Antonio; Morini, Elisa; Franchina, Fabio; Maisano, Domenica; La Rosa, Mariangela; Plota, Maria; Crifò, Adolfa; Meo, Anna; Frisina, Nicola

    2007-06-01

    Osteoporosis affects approximately 40-50% of adult patients with beta-Thalassemia Major (beta TM). Recent data have implicated an altered modulation of the osteoprotegerin (OPG)/receptor activator of NFkB ligand (RANKL) system in the pathogenesis of beta TM-osteoporosis. OPG/RANKL system acts downstream from IL-1 alpha, IL-6 and TNF-alpha and it may be the final actor mediating the effects of these cytokines on the regulation of both postmenopausal and metabolic bone resorption. However, to date, there are no data on circulating levels of these pro-resorptive cytokines in beta TM patients. We investigated the potential relationships among these cytokines, several markers of bone turnover and bone mineral density (BMD) in beta TM patients. IL-1 alpha, IL-6 and TNF-alpha, OPG and RANKL serum levels, hemato-urinary bone remodeling markers and bone mineral density (BMD) at L2L4 and femoral neck as well as erythropoietin (EPO), 17beta-estradiol, and free-testosterone levels were measured in 30 well treated beta TM patients and in 20 healthy subjects, matched for age, sex and BMI with the patients. beta TM patients showed an altered bone turnover, with increased deoxypyridinoline (D-PYR) levels (P<0.0001), decreased osteocalcin (BGP) concentrations (<0.0001) and significantly lower lumbar (P=0.001) and femoral (P<0.05) BMD values as compared to controls. Circulating levels of IL-1 alpha (P<0.0001), TNF-alpha (P<0.0001) and IL-6 (P<0.05) were all increased in beta TM patients as compared with controls. In beta TM patients, IL-1 alpha was significantly related with D-PYR (r=0.5; P<0.05), RANKL (r=0.7; P=0.03) and IL-6 (r=0.3; P=0.006); IL-6 was also significantly correlated with D-PYR (r=0.5; P<0.05) and EPO levels (r=0.3; P=0.03); TNF-alpha showed a negative correlation with L2L4 BMD (r=-0.4; P<0.05). Our data demonstrate, for the first time, an association between increased circulating levels of pro-resorptive cytokines and an altered bone turnover in beta TM

  12. Study of Serum Haptoglobin Level and its Relation to Erythropoietic Activity in Beta Thalassemia Children

    OpenAIRE

    Seham M. Ragab; Safan, Manal A.; Badr, Eman A.

    2015-01-01

    Background Serum haptoglobin (Hp) is a reliable marker for hemolysis regardless the inflammatory state. Objective We investigated the possible relation between Hp depletion and hemolysis severity, hepatitis C virus (HCV) infection and iron load in β-thalassemia children. Methods Twenty two β-thalassemia major (TM),20 β-thalassemia intermedia (TI) children with 20 age and sex matched healthy controls were involved. Pre-transfusion hemoglobin level was considered. Serum ferritin, Hp and transfe...

  13. Insulin-like growth factor-1 levels in children with Beta-thalassemia minor

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    Mehran Karimi

    2008-09-01

    Full Text Available Objective: Growth retardation in children with b-thalassemia major is multifactorial. Some etiologies described for this condition are hemochromatosis, disturbed growth hormone (GH / insulin growth factor-1 (IGF-1 axis, undernutrition and hypermetabolism. It has also been proven that growth retardation is present in b-thalassemia major children despite regular transfusion and chelation. Our aim was to evaluate the level of IGF-1 in b-thalassemia minor subjects and compare it with that in healthy children. Material and Methods: Fifty children aged 6 months to 15 years with b-thalassemia minor (32 males, 18 females and 50 age- and sex-matched normal healthy children were selected. Medical history was taken and complete physical examination was done in each case; IGF-1 level was checked in all cases. This study was done in Shiraz, southern Iran, during 2005.Results: IGF-1 levels were significantly lower in b-thalassemia minor children than normal children (P = 0.015. This result demonstrates that some etiologies of growth failure in b-thalassemia major other than those described to date can exist, which may be shared with b-thalassemia minor in feature or may be transformed by genes that are either expressed or not.Conclusion: We conclude that in addition to that observed in b-thalassemia major, IGF-1 level is also decreased in b-thalassemia minor, and these two may have similar etiologies.

  14. Síndrome de Plummer-Vinson: uma rara associação na talassemia Plumer-Vinson syndrome: a rare association with thalassemia

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    Eduardo Crema

    2007-12-01

    Full Text Available A síndrome de Plummer-Vinson é caracterizada por disfagia cervical, deficiência de ferro e presença de membrana esofágica. Neste estudo, relatam-se dois casos dessa síndrome em irmãos adolescentes. Eles não obtiveram aumento dos níveis hematimétricos após reposição com ferro oral, o que, associado à eletroforese de hemoglobinas, sustentou o diagnóstico de talassemia concomitante. Devido ao quadro dos filhos, os pais foram também submetidos à eletroforese de hemoglobinas cujo diagnóstico do pai foi talassemia alfa/beta menor e da mãe, talassemia alfa menor. Os irmãos tiveram disfagia refratária e necessitaram de dilatação endoscópica. Ambos necessitaram de terapia com ferro venoso com melhora dos níveis hematimétricos.Plummer-Vinson syndrome is characterized by cervical dysphagia, iron deficiency and the presence of esophageal membranes. We report two cases of this syndrome present in adolescent brothers with associated thalassemia. After oral iron therapy, their hematimetric levels showed no increase, which associated with the results of hemoglobin electrophoresis, sustained the diagnosis of thalassemia. Due to the condition of the children, the parents were submitted to hemoglobin electrophoresis examinations; the father was diagnosed as having minor alpha/beta thalassemia and the mother as minor beta thalassemia. Both patients suffered from refractory dysphagia and required endoscopic dilatation. They both underwent venous iron therapy, which improved the hematimetric levels.

  15. β-Thalassemia and Polycythemia vera: targeting chronic stress erythropoiesis.

    Science.gov (United States)

    Crielaard, Bart J; Rivella, Stefano

    2014-06-01

    β-Thalassemia and Polycythemia vera are genetic disorders which affect the synthesis of red blood cells, also referred to as erythropoiesis. Although essentially different in clinical presentation - patients with β-thalassemia have an impairment in β-globin synthesis leading to defective erythrocytes and anemia, while patients with Polycythemia vera present with high hemoglobin levels because of excessive red blood cell synthesis - both pathologies may characterized by lasting high erythropoietic activity, i.e. chronic stress erythropoiesis. In both diseases, therapeutic strategies targeting chronic stress erythropoiesis may improve the address phenotype and prevent secondary pathology, such as iron overload. The current review will address the basic concepts of these strategies to reduce chronic stress erythropoiesis, which may have significant clinical implications in the near future.

  16. Thermogravimetric analysis coupled with chemometrics as a powerful predictive tool for ß-thalassemia screening.

    Science.gov (United States)

    Risoluti, Roberta; Materazzi, Stefano; Sorrentino, Francesco; Maffei, Laura; Caprari, Patrizia

    2016-10-01

    β-Thalassemia is a hemoglobin genetic disorder characterized by the absence or reduced β-globin chain synthesis, one of the constituents of the adult hemoglobin tetramer. In this study the possibility of using thermogravimetric analysis (TGA) followed by chemometrics as a new approach for β-thalassemia detection is proposed. Blood samples from patients with β-thalassemia were analyzed by the TG7 thermobalance and the resulting curves were compared to those typical of healthy individuals. Principal Component Analysis (PCA) was used to evaluate the correlation between the hematological parameters and the thermogravimetric results. The thermogravimetric profiles of blood samples from β-thalassemia patients were clearly distinct from those of healthy individuals as result of the different quantities of water content and corpuscular fraction. The hematological overview showed significant decreases in the values of red blood cell indices and an increase in red cell distribution width value in thalassemia subjects when compared with those of healthy subjects. The implementation of a predictive model based on Partial Least Square Discriminant Analysis (PLS-DA) for β-thalassemia diagnosis, was performed and validated. This model permitted the discrimination of anemic patients and healthy individuals and was able to detect thalassemia in clinically heterogeneous patients as in the presence of δβ-thalassemia and β-thalassemia combined with Hb Lepore. TGA and Chemometrics are capable of predicting ß-thalassemia syndromes using only a few microliters of blood without any pretreatment and with an hour of analysis time. A fast, rapid and cost-effective diagnostic tool for the β-thalassemia screening is proposed.

  17. North Polar Cap

    Science.gov (United States)

    2004-01-01

    [figure removed for brevity, see original site] This week we will be looking at five examples of laminar wind flow on the north polar cap. On Earth, gravity-driven south polar cap winds are termed 'catabatic' winds. Catabatic winds begin over the smooth expanse of the cap interior due to temperature differences between the atmosphere and the surface. Once begun, the winds sweep outward along the surface of the polar cap toward the sea. As the polar surface slopes down toward sealevel, the wind speeds increase. Catabatic wind speeds in the Antartic can reach several hundreds of miles per hour. In the images of the Martian north polar cap we can see these same type of winds. Notice the streamers of dust moving downslope over the darker trough sides, these streamers show the laminar flow regime coming off the cap. Within the trough we see turbulent clouds of dust, kicked up at the trough base as the winds slow down and enter a chaotic flow regime. The horizontal lines in these images are due to framelet overlap and lighting conditions over the bright polar cap. Image information: VIS instrument. Latitude 86.5, Longitude 64.5 East (295.5 West). 40 meter/pixel resolution. Note: this THEMIS visual image has not been radiometrically nor geometrically calibrated for this preliminary release. An empirical correction has been performed to remove instrumental effects. A linear shift has been applied in the cross-track and down-track direction to approximate spacecraft and planetary motion. Fully calibrated and geometrically projected images will be released through the Planetary Data System in accordance with Project policies at a later time. NASA's Jet Propulsion Laboratory manages the 2001 Mars Odyssey mission for NASA's Office of Space Science, Washington, D.C. The Thermal Emission Imaging System (THEMIS) was developed by Arizona State University, Tempe, in collaboration with Raytheon Santa Barbara Remote Sensing. The THEMIS investigation is led by Dr. Philip Christensen

  18. VITAMIN D STATUS IN THALASSEMIA MAJOR: AN UPDATE

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    Ashraf Tawfik Soliman

    2013-09-01

    Full Text Available The survival of patients with thalassemia major has progressively improved with advances in therapy; however, osteoporosis and cardiac dysfunction remain frequent complications. Adequate circulating levels of vitamin D are essential for optimal skeletal health and reducing fracture risk. Vitamin D deficiency and insufficiency is reported to be high in thalassemic patients in many countries despite the presence of good sunshine and routine prescription of 400–1,000 IU vitamin D per day. The risk of vitamin D deficiency in thalassemia and its relation to bone disease; including osteoporosis, rickets, scoliosis, spinal deformities and fractures as well as to cardiac dysfunction is discussed in this mini-review. Monitoring and maintaining normal serum level of 25-OH vitamin D through oral intake of vitamin D and early correction of VDD by oral or parental use of vitamin D may significantly improve bone mineral accretion and ameliorate cardiac function. The survival of patients with thalassemia major has progressively improved with advances in therapy; however, osteoporosis and cardiac dysfunction remain frequent complications. Adequate circulating levels of vitamin D are essential for optimal skeletal health and reducing fracture risk. Vitamin D deficiency and insufficiency is reported to be high in thalassemic patients in many countries despite the presence of good sunshine and routine prescription of 400–1,000 IU vitamin D per day. The risk of vitamin D deficiency in thalassemia and its relation to bone disease; including osteoporosis, rickets, scoliosis, spinal deformities and fractures as well as to cardiac dysfunction is discussed in this mini-review. Monitoring and maintaining normal serum level of 25-OH vitamin D through oral intake of vitamin D and early correction of VDD by oral or parental use of vitamin D may significantly improve bone mineral accretion and ameliorate cardiac function.

  19. Study of ocular manifestations in children of thalassemia

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    Dhara K. Gosai

    2014-04-01

    Conclusion: Most of the ocular changes of beta thalassemia are attributed to the course and severity of the disease. Reduction in serum iron and serum Ferritin levels by iron- chelating agents and regular ocular examination to look for side-effects of such agents can aid in preventing or delaying ocular complications. [Int J Res Med Sci 2014; 2(2.000: 695-698

  20. Iron Chelation Adherence to Deferoxamine and Deferasirox in Thalassemia

    OpenAIRE

    Trachtenberg, Felicia; Vichinsky, Elliott; Haines, Dru; Pakbaz, Zahra; Mednick, Lauren; Sobota, Amy; Kwiatkowski, Janet; Thompson, Alexis A.; Porter, John; Coates, Thomas; Giardina, Patricia J.; Olivieri, Nancy; Yamashita, Robert; Neufeld, Ellis J.

    2011-01-01

    The Thalassemia Clinical Research Network collected adherence information from 79 patients on deferoxamine and 186 on deferasirox from 2007 to 2009. Chelation adherence was defined as percent of doses administered in the last 4 weeks (patient report) out of those prescribed (chart review). Chelation history since 2002 was available for 97 patients currently on deferoxamine and 217 on deferasirox, with crude estimates of adherence from chart review. Self-reported adherence to both deferoxamine...

  1. Non-transfusion dependent thalassemia: translating evidence to guidelines

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    Afif R. Harb

    2014-12-01

    Full Text Available The thalassemias are a group of inherited disorders of hemoglobin synthesis characterized by various degrees of defective production of the α- or β-globin chains of adult hemoglobin A. Non-transfusion- dependent thalassemia (NTDT includes a group of thalassemia patients who do not require regular RBC transfusions for survival, but may require occasional transfusions due to infection or pregnancy or may require more regular transfusions later in life due to splenomegaly or other complications. Due to the rising phenomenon of global migration, this previously well-localized entity is currently spreading more and more worldwide reaching Northern America and Northern Europe. The clinical picture of NTDT is governed by the severity of the ineffective erythropoiesis and the chronic hemolytic anemia, which, in turn, lead to iron overload, hypercoagulability, and an array of clinical complications involving almost every organ system. Patients with NTDT suffer from complications that are distinct from those encountered in patients with transfusion- dependent thalassemia (TDT in addition to the complications shared by both TDT and NTDT. As a consequence, patients with NTDT deserve a care specifically tailored to their needs. In the care of patients with NTDT, aiming at a standardized yet personalized care is not an easy task especially that NTDT patients lie on a heterogeneous spectrum with a wide variability in their clinical presentation and response to therapy. Therefore, guidelines emerge as a necessity to answer the specific needs of NTDT patients and the clinicians caring for them. In this article, we summarize the complications most commonly associated with NTDT and the recommendations of the guidelines for the management of patients with NTDT, based on the best available evidence.

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

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    Ruchaneekorn W. Kalpravidh

    2013-01-01

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

  3. Thalassemia: essential radiographic and clinical features of interest to dentistry

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    Luiz Roberto Coutinho Manhães Junior

    2008-01-01

    Full Text Available Thalassemia is a type of hereditary anemia that predominantly affects individuals born in or descendents of countries bathed by the Mediterranean Sea, such as Italy and Greece. Also known as Cooley’s anemia and Mediterranean anemia, the disease causes alterations in hemoglobin formation and malformations of the cranium, long bones, maxilla and mandible. It presents two distinct clinical conditions: one severe, called “major” thalassemia, and the other mild, denominated “minor” thassalemia. Hematologic exam diagnoses the two forms of the disease. Its clinical and radiographic manifestations include hepatosplenomegalia, lymphadenopathy, augmented mandible, increase in medullary spaces, thick bone trabeculae and in lower quantity, resembling a “spider web”, displacement of the mandibular canal, with loss of detail of its superior and inferior corticals and a radiographic aspect of “hair standing on end” at the surface of the cranium. Some of these manifestations are so characteristic and capable of being observed in radiographs that they form part of the dentist’s routine. This case report discusses the alterations observed in the panoramic radiograph of a patient with thalassemia diagnosed by means of hematologic exam.

  4. X-ray scattering signatures of {beta}-thalassemia

    Energy Technology Data Exchange (ETDEWEB)

    Desouky, Omar S. [Radiation Physics Department, National Center for Radiation Research and Technology (NCRRT) (Egypt); Elshemey, Wael M. [Biophysics Department, Faculty of Science, Cairo University (Egypt)], E-mail: waelelshemey@yahoo.com; Selim, Nabila S. [Radiation Physics Department, National Center for Radiation Research and Technology (NCRRT) (Egypt)

    2009-08-11

    X-ray scattering from lyophilized proteins or protein-rich samples is characterized by the presence of two characteristic broad peaks at scattering angles equivalent to momentum transfer values of 0.27 and 0.6 nm{sup -1}, respectively. These peaks arise from the interference of coherently scattered photons. Once the conformation of a protein is changed, these two peaks reflect such change with considerable sensitivity. The present work examines the possibility of characterizing the most common cause of hemolytic anaemia in Egypt and many Mediterranean countries; {beta}-thalassemia, from its X-ray scattering profile. This disease emerges from a genetic defect causing reduced rate in the synthesis of one of the globin chains that make up hemoglobin. As a result, structurally abnormal hemoglobin molecules are formed. In order to detect such molecular disorder, hemoglobin samples of {beta}-thalassemia patients are collected, lyophilized and measured using a conventional X-ray diffractometer. Results show significant differences in the X-ray scattering profiles of most of the diseased samples compared to control. The shape of the first scattering peak at 0.27 nm{sup -1}, in addition to the relative intensity of the first to the second scattering peaks, provides the most reliable signs of abnormality in diseased samples. The results are interpreted and confirmed with the aid of Fourier Transform Infrared (FTIR) spectroscopy of normal and thalassemia samples.

  5. Evaluation of cardiac functions in patients with thalassemia major

    Energy Technology Data Exchange (ETDEWEB)

    Kucuk, N.O.; Aras, G.; Sipahi, T.; Ibis, E.; Akar, N.; Soylu, A.; Erbay, G. [Ankara Univ. (Turkey). Medical School

    1999-06-01

    It is known that a blood transfusion is necessary for survival in patients with thalassemia, but it may cause myocardial dysfunction due to myocardial siderosis as in other organs. The aim of this study was to evaluate myocardial perfusion by means of stress thallium scanning (MPS) and left ventricular functions by rest radionuclide ventriculography (RNV). Twenty-one patients at ages 9-16 (mean 12.1{+-}3.2) who have been diagnosed with thalassemia for 4-15 years mean 12.7{+-}4.8) were included in the study. They had blood transfusion 78-318 times (mean 162.1{+-}71). MPS and RNV was performed within two days after the any transfusion. MPS showed ischemia in 3 patients and normal perfusion in 18 patients. RNV revealed normal systolic parameters (wall motion, EF, PER, TPE) but diminished diastolic parameters (TPF, PFR) compared with normal values (p<0.05). We conclude that ischemia or fixed defects may be seen in stress MPS as results of cardiac involvement in patients with thalassemia. But, RNV is an important and preferable test for the early detection of subclinic cardiomyopathy. RNV may therefore show diastolic abnormalities before the systolic abnormalities show up. (author)

  6. X-ray scattering signatures of β-thalassemia

    Science.gov (United States)

    Desouky, Omar S.; Elshemey, Wael M.; Selim, Nabila S.

    2009-08-01

    X-ray scattering from lyophilized proteins or protein-rich samples is characterized by the presence of two characteristic broad peaks at scattering angles equivalent to momentum transfer values of 0.27 and 0.6 nm -1, respectively. These peaks arise from the interference of coherently scattered photons. Once the conformation of a protein is changed, these two peaks reflect such change with considerable sensitivity. The present work examines the possibility of characterizing the most common cause of hemolytic anaemia in Egypt and many Mediterranean countries; β-thalassemia, from its X-ray scattering profile. This disease emerges from a genetic defect causing reduced rate in the synthesis of one of the globin chains that make up hemoglobin. As a result, structurally abnormal hemoglobin molecules are formed. In order to detect such molecular disorder, hemoglobin samples of β-thalassemia patients are collected, lyophilized and measured using a conventional X-ray diffractometer. Results show significant differences in the X-ray scattering profiles of most of the diseased samples compared to control. The shape of the first scattering peak at 0.27 nm -1, in addition to the relative intensity of the first to the second scattering peaks, provides the most reliable signs of abnormality in diseased samples. The results are interpreted and confirmed with the aid of Fourier Transform Infrared (FTIR) spectroscopy of normal and thalassemia samples.

  7. Body Composition in Adult Patients with Thalassemia Major

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    Marianna Vlychou

    2016-01-01

    Full Text Available Objective. To assess body composition in adult male and female patients with thalassemia major by dual-energy X-ray absorptiometry (DXA and to compare the findings with a group of healthy age-matched controls. Methods. Our study group included sixty-two patients (27 males, mean age 36 years, and 35 females, mean age 36.4 years and fifteen age-matched healthy controls. All patients had an established diagnosis of thalassemia major and followed a regular blood transfusion scheme since childhood and chelation treatment. Fat, lean, and bone mineral density (BMD were assessed with dual-energy X-ray absorptiometry. Ferritin levels and body mass index of all patients and controls were also recorded. Student t-test and Wilcoxon test were performed and statistical significance was set at p<0.05. Results. BMD and whole body lean mass are lower in both male and female adult patients compared with controls (p<0.01 in both groups, whereas whole body fat mass was found to have no statistically significant difference compared to controls. Regional trunk fat around the abdomen was found to be lower in male patients compared to controls (p=0.02. Conclusion. Severe bone loss and diminished lean mass are expected in adult male and female patients with thalassemia major. Fat changes seem to affect mainly male patients.

  8. Genetic counseling for thalassemia in the Islamic Republic of Iran.

    Science.gov (United States)

    Strauss, Bernard S

    2009-01-01

    The response of groups to pressing medical problems cannot be predicted on theoretical grounds. An example is the program for the control of beta-thalassemia in Iran, a country with a tradition of inbreeding and a conservative religious culture, and in which thalassemia is common. Thalassemia is largely treatable, but the treatment is lifelong and onerous and creates a serious economic burden for the individual family and for the national health budget. The genetics are simple, and inexpensive screening tests are available to identify carriers. An Iranian program requiring mandatory premarital screening was started in 1997, and between 1998 and 2005 the laws of the country were modified to permit abortion of affected fetuses. The story of this effort indicates how a country with a social system very different from that of the United States responded to a medical problem with significant ethical overtones. The Iranian experience supports the optimistic view that societies can react to pressing problems with pragmatic rather than theoretical solutions.

  9. Analysis of thalassemia genetic test among pregnants with negative hematological phenotype%血液学初筛表型阴性的孕妇地中海贫血基因检测结果分析

    Institute of Scientific and Technical Information of China (English)

    李爱敏; 唐曙明; 陈海霞; 刘彩艳

    2015-01-01

    目的:了解血液学初筛表型阴性的孕妇地中海贫血基因类型及分布,为优生优育提供参考和指导。方法用全自动血液分析仪测定病人平均红细胞体积(MCV)、平均红细胞血红蛋白含量(MCH),应用gap-PCR法检测3种缺失型α-地贫基因和膜反向杂交法检测17种β-地贫基因突变,对实验数据进行统计分析。结果在1787例地贫初筛表型阴性的孕妇中,检出地贫基因携带者52例,占总检出地贫的14.21%(52/366),其中αα/-α3.746例、-α4.2/αα3例、β地贫(均为CAP杂合子)2例、α复合β地贫(基因型-α3.7/βEM)1例,分别占检出的88.46%、5.77%、3.85%、1.92%。结论在地贫高发地区, MCV≥82fl、MCH≥27pg不能完全排除携带地贫基因的风险,基因型以αα/-α3.7为主。%Objective To investigate the genotypes and distribution of thalassemia in pregnant women with negative hemato-logical phenotype, providing reference and guidance for good prenatal and postnatal care. Methods MCV and MCH were detect-ed by hematology system. Gap-PCR was used to detect the three kinds of gene deletion of α-thalassemia and reverse dot blot ( RDB) was used to detect the17 kinds of gene mutation ofβ-thalassemia, All data from the detection was analyzed statistically. Re-sults Among 1787 pregnants with negative hematological phenotype, 52 cases of thalassemia gene carriers were detected, accouting for 14.21%(52/366) in all thalassemia gene carriers. 46 cases ofαα/-α3.7,3 cases of-α4.2/αα, 2 cases of CAP heterozygosis ofβ-thalassemia and a case ofα3.7/βEM ofα-andβ-compound thalassemia were detected, occupied 88.46%, 5.77%, 3.85%and 1.92%respectively. Conclusions In high incidence areas of thalassemia, the thalassemia gene carries couldn't be completely ruled out with MCV≥82fl、MCH≥27pg, among whom the main genotype of thalassemia detected isαα/-α3.7.

  10. Application of Domestic Full-automatic Protein Electrophoresis System in Thalassemia Screening%国产全自动蛋白电泳系统在地中海贫血筛查中应用

    Institute of Scientific and Technical Information of China (English)

    刘平

    2011-01-01

    judge the patients who whether or not suffered from thalassemia and the type of thalassemia;at the same time ,alpha and beta gene diagnosis tests had been done for all patients. Results: 181 cases alpha light-duty thalassemia, 5 cases HbH disease, 68 cases beta light-duty thalassemia,and 6 patients abnormal hemoglobin disease (including 3 HbE, 1 HbK, lHbG and 1 HbD)had been Detected and other 806 cases were phenotypic normal; but the results of genetic diagnosis showed that: 134 cases alpha light-duty thalassemia, 5 cases HbH disease, 65 cases beta light-duty thalassemia, 861 cases phenotypic normal; Comparison between screening and gene diagnosis: the diagnostic accordance rate of alpha thalassemia screening was low, only 74.03%,but HbH disease was 100% ;And the diagnostic accordance rate of beta thalassemia was higher, at 95.59%. Conclusion: The esolution of SH2020 full-automatic agarose gel electrophoresis system in the thalassemia screening is high, especially for beta thalassemia and HbH disease, but the esolution to alpha thalassemia screening is low, and there is misdiagnosis rate.

  11. Prevalence of renal tubular dysfunction in beta thalassemia minor in shiraz

    Directory of Open Access Journals (Sweden)

    Ali Moradi Nakhodcheri

    2012-02-01

    Full Text Available  Background & objective: β-Thalassemia minor is an asymptomatic hereditary disease. The first study on the relation of renal tubular dysfunction and β-thalassemia minor was performed in 2002 but those studies seem inadequate.The main goal of this study is through evaluation of renal tubular function in 100 patients with thalassemia minor. Materials & Methods: 100 patients with β- thalassemia which confirmed by hemoglobin electrophoresis and CBC as well as RBC indices were studied.14 out of 100 cases exit because of Urinary Tract Infection, diabetes mellitus or hypertension.Complete chemistry profile was performed on serum and urine of all reminder 86 patients (46 female and 40 male. Patients classified into two groups: β-thalassemia minor with anemia and without anemia. Another control group include 50 healthy individuals also considered.Then data analyzed by proper statistical methods. Results: 20 out of 86 reminder cases e.g. 24% showed at least one index of renal tubular dysfunction.58% of patients was been anemic and 42% non anemic. The most prominent tubular dysfunction was seen in a 29 years old lady with glucosuria and without anemia. conclusion: β-Thalassemia minor is common in Iran specially in Fars province. This study revealed significant renal tubular dysfunction in patient with β-thalassemia minor. So it is necessary to check out thalassemic patients for renal function tests periodically. Key words: β-thalassemia, minor,renal tubular dysfunction

  12. Minihepcidin peptides as disease modifiers in mice affected by β-thalassemia and polycythemia vera.

    Science.gov (United States)

    Casu, Carla; Oikonomidou, Paraskevi Rea; Chen, Huiyong; Nandi, Vijay; Ginzburg, Yelena; Prasad, Princy; Fleming, Robert E; Shah, Yatrik M; Valore, Erika V; Nemeth, Elizabeta; Ganz, Tomas; MacDonald, Brian; Rivella, Stefano

    2016-07-14

    In β-thalassemia and polycythemia vera (PV), disordered erythropoiesis triggers severe pathophysiological manifestations. β-Thalassemia is characterized by ineffective erythropoiesis, reduced production of erythrocytes, anemia, and iron overload and PV by erythrocytosis and thrombosis. Minihepcidins are hepcidin agonists that have been previously shown to prevent iron overload in murine models of hemochromatosis and induce iron-restricted erythropoiesis at higher doses. Here, we show that in young Hbb(th3/+) mice, which serve as a model of untransfused β-thalassemia, minihepcidin ameliorates ineffective erythropoiesis, anemia, and iron overload. In older mice with untransfused β-thalassemia, minihepcidin improves erythropoiesis and does not alter the beneficial effect of the iron chelator deferiprone on iron overload. In PV mice that express the orthologous JAK2 mutation causing human PV, administration of minihepcidin significantly reduces splenomegaly and normalizes hematocrit levels. These studies indicate that drug-like minihepcidins have a potential as future therapeutics for untransfused β-thalassemia and PV.

  13. COMBINED USE OF ERYTHROCYTE ZINC PROTOPORPHYRINE AND MCV: DIFFERENTIATION OF BETA THALASSEMIA FROM IRON DEFICIENCY ANEMIA

    Directory of Open Access Journals (Sweden)

    H KHOSHAMOOZ

    2001-12-01

    Full Text Available Introduction: Due to the prevalence of beta thalassemia and iron deficiency anemia in Irana need for an accurate, quick, inexpensive and simple method for differential diagnosis between these two disorders is felt. In this study the value of zpp measurement as a tool to distinguish iron deficiency from heterozygous beta thalassemia in microcrystal patients was evaluated. Methods: In this study on 140 persons with microcytosis, the hemoglobin electrophoresis, serum iron, TIBC and serum ferritin and protoporphyrine relating to zinc (ZPP were measured. Results: ZPP had been increased in all iron deficient patients and in 53 percent of Heterozygote beta thalassemia patients. Using combination of MCV and ZPP in iron deficient anemic patients and heterozygote beta thalassemia show the 99 percent accuaracy in differentiation of these two disorders. Discussion: According to the results, this method has better accuracy than red blood cells formulation in the screening programs for beta thalassemia and iron defficiency anemia.

  14. 骨髓增生异常综合征伴获得性α地中海贫血中X连锁α地中海贫血伴智力障碍基因突变的研究进展%Ressearch progress of α-Thalassemia mental retardation X-linked gene mutation of acquired α-Thalassemia myelodystic syndrome

    Institute of Scientific and Technical Information of China (English)

    郑鹏茜

    2015-01-01

    α地中海贫血多由第16号染色体异常引起的遗传性疾病,在恶性血液肿瘤疾病中,尤其是骨髓增生异常综合征(MDS),发现α地中海贫血可作为获得性疾病出现,称为骨髓增生异常综合征伴获得性α-地中海贫血(ATMDS),其机制与体细胞发生X连锁α地中海贫血伴智力障碍(ATRX)基因突变相关.越来越多的研究结果表明ATRX基因编码产物可作为反式作用因子可调节α珠蛋白表达.通过对ATRX蛋白功能的分析,从染色质重塑、调控基因表达等分子机制阐明ATRX基因、ATRX蛋白、α珠蛋白在ATMDS发生、发展中的内在联系,有助于在分子机制水平阐释ATMDS临床表现.%Alpha-thalassemia is a common inherited form of anemia that usually results from dysfunction of the chromosome 16.Acquired alpha-thalassemia associated with somatic mutation in alpha thalassemia mental retardation X-linked (ATRX) gene has been found in patients who develop neoplastic myeloid disorders,especially myelodystic syndrome (MDS).So it is called acquired alpha-thalassemia myelodystic syndrome(ATMDS).A majority of researches suggested the protein encoded by ATRX gene functions as a trans-acting factor regulates expression of α-globin.Summarizing studies on function of ATRX protein,such as chromatin remodeler and gene regulation,we elucidate the association among ATRX gene,ATRX protein and α-globin in the development of ATMDS.It helps us explain ATMDS symptoms in terms of molecular mechanisms.

  15. Hepatic lesions and hemolysis following administration of 3. cap alpha. , 7. cap alpha. , 12. cap alpha. -trihydroxy-5. beta. -cholestan-26-oyl taurine to rats

    Energy Technology Data Exchange (ETDEWEB)

    Hanson, R.F. (Univ. of Minnesota, Minneapolis); Williams, G.C.; Hachey, D.; Sharp, H.L.

    1977-09-01

    Patients with a metabolic block in the conversion of THCA into cholic acid develop cirrhosis and hemolysis, and die of hepatic failure. In these patients, THCA is largely conjugated to taurine (tauro-THCA) and excreted instead of being converted into cholic acid. In the present study, the effects of tauro-THCA on hemolysis, bile flow, and hepatic morphology were evaluated in bile fistula rats. All rats infused with tauro-THCA at rates of 0.25, 0.50 or 0.75 ..mu..mol/min developed hemolysis with hemoglobinuria. A direct toxic effect of tauro-THCA on washed human red blood cell membranes was demonstrated at a concentration of 8 x 10/sup -4/ M. Liver biopsy sections from rats infused for a 2 hr period with tauro-THCA were examined by electron microscopy and showed dilation of the rough endoplasmic reticulum and distortion of mitochondrial membranes. Cholestasis was not induced, since tauro-THCA actually caused a greater choleretic response for a given rate of bile salt excretion than did taurocholate. This study raises the possibility that the clinical liver disease seen in patients with a metabolic block in the conversion of THCA into cholic acid may be caused by tauro-THCA.

  16. Saltstone Clean Cap Formulation

    Energy Technology Data Exchange (ETDEWEB)

    Langton, C

    2005-04-22

    The current operation strategy for using Saltstone Vault 4 to receive 0.2 Ci/gallon salt solution waste involves pouring a clean grout layer over the radioactive grout prior to initiating pour into another cell. This will minimize the radiating surface area and reduce the dose rate at the vault and surrounding area. The Clean Cap will be used to shield about four feet of Saltstone poured into a Z-Area vault cell prior to moving to another cell. The minimum thickness of the Clean Cap layer will be determined by the cesium concentration and resulting dose levels and it is expected to be about one foot thick based on current calculations for 0.1 Ci Saltstone that is produced in the Saltstone process by stabilization of 0.2 Ci salt solution. This report documents experiments performed to identify a formulation for the Clean Cap. Thermal transient calculations, adiabatic temperature rise measurements, pour height, time between pour calculations and shielding calculations were beyond the scope and time limitations of this study. However, data required for shielding calculations (composition and specific gravity) are provided for shielding calculations. The approach used to design a Clean Cap formulation was to produce a slurry from the reference premix (10/45/45 weight percent cement/slag/fly ash) and domestic water that resembled as closely as possible the properties of the Saltstone slurry. In addition, options were investigated that may offer advantages such as less bleed water and less heat generation. The options with less bleed water required addition of dispersants. The options with lower heat contained more fly ash and less slag. A mix containing 10/45/45 weight percent cement/slag/fly ash with a water to premix ratio of 0.60 is recommended for the Clean Cap. Although this mix may generate more than 3 volume percent standing water (bleed water), it has rheological, mixing and flow properties that are similar to previously processed Saltstone. The recommended

  17. Structure of the N-terminal domain of the adenylyl cyclase-associated protein (CAP) from Dictyostelium discoideum.

    Science.gov (United States)

    Ksiazek, Dorota; Brandstetter, Hans; Israel, Lars; Bourenkov, Gleb P; Katchalova, Galina; Janssen, Klaus-Peter; Bartunik, Hans D; Noegel, Angelika A; Schleicher, Michael; Holak, Tad A

    2003-09-01

    Cyclase-associated proteins (CAPs) are widely distributed and highly conserved proteins that regulate actin remodeling in response to cellular signals. The N termini of CAPs play a role in Ras signaling and bind adenylyl cyclase; the C termini bind to G-actin and thereby alter the dynamic rearrangements of the microfilament system. We report here the X-ray structure of the core of the N-terminal domain of the CAP from Dictyostelium discoideum, which comprises residues 51-226, determined by a combination of single isomorphous replacement with anomalous scattering (SIRAS). The overall structure of this fragment is an alpha helix bundle composed of six antiparallel helices. Results from gel filtration and crosslinking experiments for CAP(1-226), CAP(255-464), and the full-length protein, together with the CAP N-terminal domain structure and the recently determined CAP C-terminal domain structure, provide evidence that the functional structure of CAP is multimeric.

  18. Bone marrow transplantation for thalassemia: a global perspective

    Directory of Open Access Journals (Sweden)

    Mohamed Hamed Hussein

    2013-03-01

    Full Text Available Even though severe thalassemia is a preventable disease, over 100,000 new cases are born yearly, particularly in the Middle East and South-East Asia. Most of these children may not reach adulthood because long-term appropriate supportive care is either inaccessible or unaffordable. Bone marrow transplantation (BMT remains the only available definitive cure and success rates can be very high in appropriately selected patients, i.e. low-risk younger children with a matched family donor. In these circumstances BMT may be justified medically, ethically as well as financially, in fact, the cost of low-risk BMT is equivalent to that of a few years of non-curative supportive. This manuscript will briefly review the current status of bone marrow transplantation for thalassemia major with particular emphasis on a global prospective and present the experience of the Cure2Children Foundation supporting sustainable and scalable start up BMT programs in low-resource settings. The initial twelve consecutive patients managed in two start up BMT units in Pakistan (Children’s Hospital of the Pakistan Institute of Medical Sciences, Islamabad and India (South East Asia Institute for Thalassemia, Jaipur were included in this analysis. These initial six patients per each institution where purposely chosen as the focus of this report because they represent the steepest phase of the learning curve. The median age at transplant was 3.9 years, range 0.9 to 6.0, liver was no greater than 2 cm from costal margin, and all received matched related BMT. A structured on-site focused training program as well as ongoing intensive on-line cooperation was provided by the Cure2Children team of professionals. At a median follow-up of 7.5 months (range 3.5 to 33.5 months both thalassemia-free and overall survival are 92%, one patient died of encephalitis-meningitis of unknown cause. No rejections where observed. Neutrophil recovery occurred at a median of 15.5 days (range 13

  19. Polar Cap Retreat

    Science.gov (United States)

    2004-01-01

    13 August 2004 This red wide angle Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows a view of the retreating seasonal south polar cap in the most recent spring in late 2003. Bright areas are covered with frost, dark areas are those from which the solid carbon dioxide has sublimed away. The center of this image is located near 76.5oS, 28.2oW. The scene is large; it covers an area about 250 km (155 mi) across. The scene is illuminated by sunlight from the upper left.

  20. Human parvovirus B19 in patients with beta thalassemia major from Tehran, Iran

    Science.gov (United States)

    Arabzadeh, Seyed Ali Mohammad; Alizadeh, Farideh; Tavakoli, Ahmad; Mollaei, Hamidreza; Bokharaei-Salim, Farah; Karimi, Gharib; Farahmand, Mohammad; Mortazavi, Helya Sadat

    2017-01-01

    Background Due to the tropism of human parvovirus B19 to erythroid progenitor cells, infection in patients with an underlying hemolytic disorder such as beta-thalassemia major leads to suppression of erythrocyte formation, referred to as transient aplasia crisis (TAC), which may be life-threatening. We investigated the prevalence of parvovirus B19 among patients with beta thalassemia major attending the Zafar Adult Thalassemia Clinic in Tehran, Iran. Methods This cross-sectional study was performed to determine the presence of parvovirus B19 DNA in blood samples and parvovirus B19 genotypes in plasma samples of patients with thalassemia major. The population consisted of 150 patients with beta-thalassemia major who attended the Zafar clinic in Tehran. Specimens were studied using a real-time polymerase chain reaction assay. Results The prevalence of parvovirus B19 in our study population was 4%. Of 150 patients with thalassemia, six (4%) were positive for B19 DNA. There was no significant correlation between blood transfusion frequency and B19 DNA positivity. Finally, phylogenetic analysis of human parvovirus B19 revealed genotype I in these six patients. Conclusion In this study, acute B19 infections were detected in patients with beta thalassemia major. Screening of such high-risk groups can considerably reduce the incidence and prevalence of B19 infection; thus, screening is required for epidemiologic surveillance and disease-prevention measures.

  1. Combined Chelation Therapy with Deferasirox and Deferoxamine in Thalassemia

    OpenAIRE

    Lal, Ashutosh; Porter, John; Sweeters, Nancy; Ng, Vivian; Evans, Patricia; Neumayr, Lynne; Kurio, Gregory; Harmatz, Paul; Vichinsky, Elliott

    2012-01-01

    Iron overload is the primary cause of mortality and morbidity in thalassemia major despite advances in chelation therapy. We performed a pilot clinical trial to evaluate the safety and efficacy of combined therapy with deferasirox (DFX, 20-30 mg/kg daily) and deferoxamine (DFO, 35-50 mg/kg on 3-7 days/week) in 22 patients with persistent iron overload or organ damage. In the 18 subjects completing 12 months of therapy, median liver iron concentration decreased by 31% from 17.4 mg/g (range 3.9...

  2. Physical growth in children with transfusion-dependent thalassemia

    Directory of Open Access Journals (Sweden)

    Harish K Pemde

    2011-02-01

    Full Text Available Harish K Pemde, Jagdish Chandra, Divya Gupta, Varinder Singh, Rajni Sharma, AK DuttaDepartment of Pediatrics, Lady Hardinge Medical College, Kalawati Saran Children's Hospital, New Delhi, IndiaObjective: To describe physical growth and related factors in transfusion-dependent thalassemia patients.Methods: This is a cross-sectional analysis of the records of the patients registered at and being followed up by the Thalassemia Day Care Center (TDCC at Kalawati Saran Children's Hospital, New Delhi, India. Clinical and laboratory parameters were recorded on a spreadsheet for analysis. Clinical parameters included weight, height, sexual maturity ratings, and general and systemic physical examination. Laboratory parameters included pretransfusion hemoglobin (Hb, periodic serum ferritin, and tests for viral markers of human immunodeficiency virus (HIV and hepatitis B and C. Z-scores for weight, height, and body mass index (BMI were calculated using World Health Organization reference data. Statistical analysis was carried out using Microsoft Excel® and Stata® software.Results: Out of 214 patients registered at the TDCC since 2001, 154 were included in this study. The mean age of patients was 9.19 years (range 0.5–20 years. Pretransfusion Hb was well maintained (mean 9.21 g/dL; 95% confidence interval [CI]: 9.06–9.36, but the mean serum ferritin levels were approximately three times (3112 ng/mL the desired value despite the patients being on deferiprone (72% or deferasirox (25%. One-third (33.11% of the patients had short stature, 13% were thin, and 10.82% were very thin (BMI z-score <-3. No patient was overweight or obese. Linear regression coefficient showed that for every 1-year increase in age, the mean ferritin value increased by 186.21 pg/mL (95% CI: 143.31–228.27. Height z-scores had significant correlation with mean ferritin levels, whereas correlation with mean pretransfusion Hb was not significant statistically. Mean ferritin levels

  3. Evaluation of Endocrine Complications in Patients with Thalassemia Major

    Directory of Open Access Journals (Sweden)

    Birol Baytan

    2008-10-01

    Full Text Available Aim: Multiple blood transfusions in beta thalassemia patients causes iron overload in various tissues including endocrine glands thereby leading to multiple endocrine dysfunction. The aim of this study was to determine the endocrine complications seen in beta thalassemia patients followed-up in outpatient clinics of Pediatric Hematology Division of Uludag University Faculty of Medicine. Materials and Methods: The files of patients with thalassemia major followed-up in outpatient clinics of Pediatric Hematology Division of Uludag University Faculty of Medicine from January 1976 to August 2008 were retrospectively evaluated for endocrine disorders. All patients had a detailed physical examination including palpation of thyroid gland and pubertal staging. Endocrine evaluation was performed in the Division of Pediatric Endocrinology.Results: A total of 44 [20 female (45.5%; 24 male (54.5%; and mean chronological age 13.54±7.32 (2.75-35.2 years] patients were evaluated. The ratios of patients with endocrine dysfunction were 27.2 % and 90.9%, respectively, when we exclude or include those with osteoporosis/osteopenia or growth failure other than growth hormone deficiency. Of all patients, 27 (61.3% had osteoporosis, 17 (38.6% had growth retardation, 11 (25% had osteopenia, 6 (13.6% had hypogonadism, 3 (6.8% had hypothyroidism, 2 (4.5% had hypoparathyroidism, 1 (2.3 had growth hormone deficiency, and 1 (2.3 had type 1 diabetes mellitus. Mean ferritin levels and monthly transfusion numbers were 1976.15±1494.75 ng/ml and 1.46±0.34, respectively. There were no significant association between ferritin levels, monthly transfusion needs, and endocrine dysfunctions studied. Endocrine dysfunctions did not differ significantly amongst those having different chelating agents. The ratio of patients with growth retardations in 10 to 19-age-group was significantly higher than those in 0 to 9-age-group (30.6% vs 8.3%; p=0.049. Conclusion: Patients with

  4. Reactivation of fetal hemoglobin in thalassemia and sickle cell disease

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    Sandro Eridani

    2014-09-01

    Full Text Available Considerable attention has been recently devoted to mechanisms involved in the perinatal hemoglobin switch, as it was long ago established that the survival of fetal hemoglobin (HbF production in significant amount can reduce the severity of the clinical course in severe disorders like β-thalassemia and sickle cell disease (SCD. For instance, when β-thalassemia is associated with hereditary persistence of fetal hemoglobin (HPFH the disease takes a mild course, labeled as thalassemia intermedia. The same clinical amelioration occurs for the association between HPFH and SCD. As for the mechanism of this effect, some information has been obtained from the study of natural mutations at the human β-globin locus in patients with increased HbF, like the Corfu thalassemia mutations. Important evidence came from the discovery that drugs capable of improving the clinical picture of SCD, like decitabine ad hydroxycarbamide, are acting through the reactivation, to some extent, of HbF synthesis. The study of the mechanism of action of these compounds was followed by the identification of some genetic determinants, which promote this event. In particular, among a few genetic factors involved in this process, the most relevant appears the BCL11A gene, which is now credited to be able to silence γ-globin genes in the perinatal period by interaction with several erythroid-specific transcription factors and is actually considered as a barrier to HbF reactivation by known HbF inducing agents. Epigenetics is also a player in the process, mainly through DNA demethylation. This is certified by the recent demonstration that hypomethylating agents such as 5-azacytidine and decitabine, the first compounds used for HbF induction by pharmacology, act as irreversible inhibitors of demethyltransferase enzymes. Great interest has also been raised by the finding that several micro-RNAs, which act as negative regulators of gene expression, have been implicated in the

  5. Thalassemia in the United Arab Emirates: Why it can be prevented but not eradicated

    Science.gov (United States)

    2017-01-01

    Thalassemia is a genetic blood disorder that causes abnormal hemoglobin. Hemoglobin is a protein in red blood cells that carries oxygen and is made of two proteins from four α-globin genes and two β-globin genes. A defect in one or more of these genes causes thalassemia. The treatment of thalassemia mostly depends on life-long blood transfusions and removal of excessive iron from the blood stream. Such tremendous blood consumption puts pressure on the national blood stock in many countries. In particular, in the United Arab Emirates (UAE), various forms of thalassemia prevention have been used and hence, the substantial reduction of the thalassemia major population has been achieved. However, the thalassemia carrier population still remains high, which leads to the potential increase in the thalassemia major population through carrier-carrier marriages. In this work, we investigate the long-term impact and efficacy of thalassemia prevention measures via mathematical modeling at a population level. To our best knowledge, this type of assessment has not been done before and there is no mathematical model that has investigated such a problem for thalassemia or any blood disorders at a population level. By using UAE data, we perform numerical simulations of our model and conduct sensitivity analysis of parameter values to see which parameter values affect most the dynamics of our model. We discover that the prevention measures can contribute to reduce the prevalence of the disease only in the short term but not eradicate the disease in the long term. PMID:28135306

  6. Preliminary Study on Thalassemia Screening and Genetic Counseling in Selective Hmong People in Saraburi Province, Thailand

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    Pa Vang

    2008-01-01

    Full Text Available it can lead to the destruction of red blood cells. Studies have shown that there is a high prevalence of thalassemia in Southeast Asia. The Institute of Health Research, Chulalongkorn University developed a successful “Module” to screen for thalassemia in the Thai population, however, it has not been implemented in the minority population in Thailand. In this study, we investigated the feasibility of the newly developed educational and thalassemia screening program with the Hmong population. The primary aim of this study was to test this program. The secondary aim was to determine the prevalence of thalassemia in the Hmong and provide education. A third aim was to determine the reliability of two different screening methods in the Hmong population. A pre-test and post-test design was used; participants (N=12 were individuals residing in Thailand with the ability to read English and between the ages 18-50. The participants met twice with the researchers to complete the program. The first contact consisted of assessing participants’ knowledge about thalassemia, providing thalassemia information and education about genetic counseling, and drawing blood samples. The second contact consisted of assessing knowledge, providing a written report of individual blood sample results and counseling. The initial interview revealed that the majority of the participants (82% did not know anything about thalassemia prior to participation. The program was easy to understand by most participants (90%. Of the eleven Hmong participants, two tested positive for being a possible carrier for thalassemia. In order to reduce the prevalence of thalassemia, it is necessary to engage in risk reduction health services. The modified screening method proved to be as effective as the standard method. Therefore, the program can expand and be used in other regional populations with low cost.

  7. Erythrocyte reference values in Emirati people with and without α+ thalassemia

    Directory of Open Access Journals (Sweden)

    Showqi Saad

    2011-02-01

    Full Text Available Abstract Background Interpreting the erythroid lineage in populations with high frequency of α+ thalassemia allele is challenging due to the high prevalence of α+ thalassemia homozygotes. For such populations, separate reference values for normal and α+ thalassemia homozygotes are needed. Methods We studied the erythroid lineage in 1,079 citizens of United Arab Emirates (UAE. Subjects with abnormal hemoglobin (39, iron deficiency (136 or erroneous entries (8 were excluded. MCV distribution in the remaining individuals (896 was visibly bimodal. Statistical mixture analysis with Normix program was used to separate subpopulations with normal and small red cells. Hardy-Weinberg equation was used to estimate genotype frequencies. Results MCV of 78.0 fl separated phenotype-derived normal homozygotes (715 from phenotype-derived α+ thalassemia homozygotes (181. The erythrocyte indices were significantly different between the two groups (p + thalassemia homozygotes (-α/-α was 0.20 and markedly varied among tribes, 0 to 0.31 (Mean = 0.15. The frequency of phenotype-derived α+ thalassemia allele was 0.44; when accounting for tribal population structure and inbreeding, the calculated frequency was 0.34. These values were very similar to those found in the same population by genotyping and other phenotyping methods. The erythrocyte reference values for phenotype-derived normal homozygotes in Emiratis closely overlapped with those for Caucasians and normal homozygotes defined by genotyping. The reference values for phenotype-derived α+ thalassemia homozygotes in Emiratis also closely overlapped with those for α+ thalassemia homozygotes defined by genotyping. Conclusion In populations with frequent α+ thalassemia mutations, two sets of erythrocyte reference values could be determined without genotyping.

  8. Novel Βeta (β)-Thalassemia Mutation in Turkish Children

    OpenAIRE

    2014-01-01

    Beta (β)-thalassemia is the most frequently observed hereditary blood disorder in the world. It is characterized by deficiency of hemoglobin β-globin gene and is also a profoundly heterogeneous both at the molecular and clinical level. In the case of β-thalassemia, there is reduced (β+ type) or absent (βo type) synthesis of the beta chains of hemoglobin. β-Thalassemia clinically occurs in three main forms: major, intermedia and minor according to requirement of transfusion. The objective of t...

  9. CARMIL is a bona fide capping protein interactant.

    Science.gov (United States)

    Remmert, Kirsten; Olszewski, Thomas E; Bowers, M Blair; Dimitrova, Mariana; Ginsburg, Ann; Hammer, John A

    2004-01-23

    CARMIL, also known as Acan 125, is a multidomain protein that was originally identified on the basis of its interaction with the Src homology 3 (SH3) domain of type I myosins from Acanthamoeba. In a subsequent study of CARMIL from Dictyostelium, pull-down assays indicated that the protein also bound capping protein and the Arp2/3 complex. Here we present biochemical evidence that Acanthamoeba CARMIL interacts tightly with capping protein. In biochemical preparations, CARMIL copurified extensively with two polypeptides that were shown by microsequencing to be the alpha- and beta-subunits of Acanthamoeba capping protein. The complex between CARMIL and capping protein, which is readily demonstratable by chemical cross-linking, can be completely dissociated by size exclusion chromatography at pH 5.4. Analytical ultracentrifugation, surface plasmon resonance and SH3 domain pull-down assays indicate that the dissociation constant of capping protein for CARMIL is approximately 0.4 microm or lower. Using CARMIL fusion proteins, the binding site for capping protein was shown to reside within the carboxyl-terminal, approximately 200 residue, proline-rich domain of CARMIL. Finally, chemical cross-linking, analytical ultracentrifugation, and rotary shadowed electron microscopy revealed that CARMIL is asymmetric and that it exists in a monomer dimer equilibrium with an association constant of 1.0 x 10(6) m(-1). Together, these results indicate that CARMIL self-associates and interacts with capping protein with affinities that, given the cellular concentrations of the proteins ( approximately 1 and 2 microm for capping protein and CARMIL, respectively), indicate that both activities should be physiologically relevant.

  10. Novel Multipin Electrode Cap System for Dry Electroencephalography.

    Science.gov (United States)

    Fiedler, P; Pedrosa, P; Griebel, S; Fonseca, C; Vaz, F; Supriyanto, E; Zanow, F; Haueisen, J

    2015-09-01

    Current usage of electroencephalography (EEG) is limited to laboratory environments. Self-application of a multichannel wet EEG caps is practically impossible, since the application of state-of-the-art wet EEG sensors requires trained laboratory staff. We propose a novel EEG cap system with multipin dry electrodes overcoming this problem. We describe the design of a novel 24-pin dry electrode made from polyurethane and coated with Ag/AgCl. A textile cap system holds 97 of these dry electrodes. An EEG study with 20 volunteers compares the 97-channel dry EEG cap with a conventional 128-channel wet EEG cap for resting state EEG, alpha activity, eye blink artifacts and checkerboard pattern reversal visual evoked potentials. All volunteers report a good cap fit and good wearing comfort. Average impedances are below 150 kΩ for 92 out of 97 dry electrodes, enabling recording with standard EEG amplifiers. No significant differences are observed between wet and dry power spectral densities for all EEG bands. No significant differences are observed between the wet and dry global field power time courses of visual evoked potentials. The 2D interpolated topographic maps show significant differences of 3.52 and 0.44% of the map areas for the N75 and N145 VEP components, respectively. For the P100 component, no significant differences are observed. Dry multipin electrodes integrated in a textile EEG cap overcome the principle limitations of wet electrodes, allow rapid application of EEG multichannel caps by non-trained persons, and thus enable new fields of application for multichannel EEG acquisition.

  11. THE IMPACT OF IRON DEFICIENCY ON HBA2 LEVEL IN BETA THALASSEMIA MINOR IN SULAIMANI NORTHEASTERN IRAQ

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    Awaz Ahmed Kamal

    2015-11-01

    Full Text Available Background: HbA2 plays a key role in screening programs for beta thalassemia because a small increase in this fraction is the most important marker of beta thalassemia heterozygous carriers. The potential impact of coincident iron deficiency on HbA2 based identification of beta thalassemia minor is worrisome issue for screening laboratories, this is especially true for resource-constrained settings where iron deficiency is wide spread and molecular confirmatory tests for borderline HbA2 values may be unavailable. Objective: the aim of this study is to evaluate the effect of iron deficiency on HbA2 level in order to improve the detection of beta thalassemia trait with or without iron deficiency in our population. Materials and Method: In this study 145 individuals were enrolled including normal controls (50, beta thalassemia minor (50 and coincident beta thalassemia with iron deficiency cases (45. Complete blood count, serum iron, total iron binding capacity and HbA2 with HbF estimation were done for every individual. Result: The mean HbA2 level was (2.4± 0.4 in control, (5.2 ± 0.9 in beta thalassemia minor and 5.1± 0.9 in coincident iron deficiency with beta thalassemia minors. All hematological parameters were significantly lower in beta thalassemia minor and coincident iron deficiency with beta thalassemia minor in comparison to the control group .Mean HbA2 level did not show a significant difference in thalassemia minor (5.2±0.9 when compared with the mean HbA2 levels in coincidentiron deficiency with beta thalassemia minor. Conclusion: The presence of iron deficiency did not preclude the detection of beta thalassemia minor in our population

  12. Hemoglobin Interlaken in combination with beta thalassemia trait

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    Mara J. Ojeda

    2013-01-01

    Full Text Available We report a rare a1 globin gene variant (Hb Interlaken found in a 63-year-old woman of Italian ancestry living in Buenos Aires Province, Argentina. The variant, a missense mutation at cd15 (GGT → GAT causing a Gly →Asp amino acid substitution and also known as Hb J Oxford, was found in combination with the common thalassemia trait cd 39 (C→T. The clinical picture of the patient was that of a b-thalassemia trait. 我们曾报道在阿根廷布宜诺斯艾利斯一名63岁意大利血统的妇女体内发现罕有的1珠蛋白基因(因特拉肯血红蛋白)变体。研究发现该变体是导致Gly → Asp氨基酸置的错义突变,也称为Hb J Oxford,与常见的地中海贫血性症cd 39 (C → T)有关。该患者临床症状与乙型地中海贫血特征相同。

  13. Current recommendations for chelation for transfusion-dependent thalassemia.

    Science.gov (United States)

    Kwiatkowski, Janet L

    2016-03-01

    Regular red cell transfusions used to treat thalassemia cause iron loading that must be treated with chelation therapy. Morbidity and mortality in thalassemia major are closely linked to the adequacy of chelation. Chelation therapy removes accumulated iron and detoxifies iron, which can prevent and reverse much of the iron-mediated organ injury. Currently, three chelators are commercially available--deferoxamine, deferasirox, and deferiprone--and each can be used as monotherapy or in combination. Close monitoring of hepatic and cardiac iron burden is central to tailoring chelation. Other factors, including properties of the individual chelators, ongoing transfusional iron burden, and patient preference, must be considered. Monotherapy generally is utilized if the iron burden is in an acceptable or near-acceptable range and the dose is adjusted accordingly. Combination chelation often is employed for patients with high iron burden, iron-related organ injury, or where adverse effects of chelators preclude administration of an appropriate chelator dose. The combination of deferoxamine and deferiprone is the best studied, but increasing data are available on the safety and efficacy of newer chelator combinations, including deferasirox with deferoxamine and the oral-only combination of deferasirox with deferiprone. The expanding chelation repertoire should enable better control of iron burden and improved outcomes.

  14. Anesthetic management of a patient with sickle β+ thalassemia

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    Saswata Bharati

    2011-01-01

    Full Text Available Sickle cell disease is a congenital condition and its most common clinical manifestation is anemia due to chronic hemolysis. Persistent and accelerated hemolysis associated with multiple transfusions is a recognized risk factor for the development of cholelithiasis. The occurrence of gallstones is one of the most important manifestations of sickle cell disease in the digestive tract. Most gallstones are pigmented and characteristically occur at younger ages and the prevalence of cholelithiasis increases progressively with age, affecting 50% of young adults. Cholecystectomy is the most common surgical procedure performed in sickle cell disease patients. Anesthesia in this population of patients for major surgeries deserves special attention due to various complications particularly silent infarctions of end organs are common. We are reporting a 14-year-old girl diagnosed with sickle cell anemia and β+ thalassemia with cholelithiasis went for cholecystectomy under general anesthesia. Although the patient has both β+ thalassemia and sickle cell disease component, the latter is of more concern for anesthesia.

  15. Deferasirox in Indian children with thalassemia major: 3 years experience

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    Mayank Dhamija

    2013-01-01

    Full Text Available Objective: To evaluate the efficacy and safety of the oral iron chelator deferasirox in treating transfusional hemosiderosis in a cohort of Indian children with thalassemia major with high iron load. Materials and Methods: The first 50 children (age 2-18 yrs with thalassemia major to commence deferasirox at our center were enrolled and followed up for a period of 36 months between April 2008 and March 2011. The dose of deferasirox was determined by their baseline serum ferritin and was adjusted to a maximum of 40 mg/kg/day depending on response. Ferritin levels, SGOT, SGPT, serum creatinine and urine albumin were regularly monitored. Results: Of the 50 patients, 76% documented a significant decline in serum ferritin ( P<0.05. Seven (14% patients had a stable ferritin whilst 5 patients (10% documented an increase over the study period. The mean serum ferritin at baseline, 12, 24 and 36 months was 4354, 3260, 3290 and 3042, respectively ( P<0.05. The median serum ferritin at the same time points was 3555, 2810, 2079 and 2271, respectively ( P<0.05. No severe toxicity was seen. Conclusions: Deferasirox, when given in doses ≥30 mg/kg, was found to be an effective and safe drug in reducing transfusional hemosiderosis. Thirty five (70% needed dose escalation upto 40 mg/kg/day. Fifteen (30%, however did not achieve a negative iron balance despite maximally permissible doses.

  16. Deferasirox in Indian children with thalassemia major: 3 years experience

    Science.gov (United States)

    Dhamija, Mayank; Mahajan, Amita; Kalra, Manas; Virmani, Anju

    2013-01-01

    Objective: To evaluate the efficacy and safety of the oral iron chelator deferasirox in treating transfusional hemosiderosis in a cohort of Indian children with thalassemia major with high iron load. Materials and Methods: The first 50 children (age 2-18 yrs) with thalassemia major to commence deferasirox at our center were enrolled and followed up for a period of 36 months between April 2008 and March 2011. The dose of deferasirox was determined by their baseline serum ferritin and was adjusted to a maximum of 40 mg/kg/day depending on response. Ferritin levels, SGOT, SGPT, serum creatinine and urine albumin were regularly monitored. Results: Of the 50 patients, 76% documented a significant decline in serum ferritin (P<0.05). Seven (14%) patients had a stable ferritin whilst 5 patients (10%) documented an increase over the study period. The mean serum ferritin at baseline, 12, 24 and 36 months was 4354, 3260, 3290 and 3042, respectively (P<0.05). The median serum ferritin at the same time points was 3555, 2810, 2079 and 2271, respectively (P<0.05). No severe toxicity was seen. Conclusions: Deferasirox, when given in doses ≥30 mg/kg, was found to be an effective and safe drug in reducing transfusional hemosiderosis. Thirty five (70%) needed dose escalation upto 40 mg/kg/day. Fifteen (30%), however did not achieve a negative iron balance despite maximally permissible doses. PMID:23878481

  17. Bone Mineral Density in Thalassemia Major Patients from Antalya, Turkey

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    Ibrahim Aslan

    2012-01-01

    Full Text Available Aim. We assessed the bone mineral density and related parameters in nine adults, thirty-eight pubertal, prepubertal totally forty-seven patients with thalassemia major living in Antalya, Turkey. Materials and Methods. We measured height and pubertal staging in last five years by six-month intervals. Average ferritin and hemoglobin concentrations were calculated for last three years. The levels of hydroxyproline, calcium, phosphorus, and creatinine were measured in 24 h urine, and those of parathormone, IGF 1, osteocalcine, alkaline phosphatase, calcium, ionized calcium, magnesium, phosphorus, creatine, blood glucose, thyroid stimulating hormone, alanine transaminase, and aspartate transaminase were determined in serum, and also the bone mineral density was measured. Results. The average L1–L4 bone mass density was 27.1±10.1 g cm−2; the average bone mineral content was 0.65 ± 0.11 g. of the patients with a Z-score under 2.5. A moderate relationship was found between the bone mass density age and height. Subjects in low pubertal staging and short stature (<3% percentile have significantly lower bone mass densities P<0.001. Conclusion. he prevalence of osteoporosis is high in patients with thalassemia major, possibly related to delayed puberty.

  18. -Thalassemia: HiJAKing Ineffective Erythropoiesis and Iron Overload

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    Luca Melchiori

    2010-01-01

    Full Text Available -thalassemia encompasses a group of monogenic diseases that have in common defective synthesis of -globin. The defects involved are extremely heterogeneous and give rise to a large phenotypic spectrum, with patients that are almost asymptomatic to cases in which regular blood transfusions are required to sustain life. As a result of the inefficient synthesis of -globin, the patients suffer from chronic anemia due to a process called ineffective erythropoiesis (IE. The sequelae of IE lead to extramedullary hematopoiesis (EMH with massive splenomegaly and dramatic iron overload, which in turn is responsible for many of the secondary pathologies observed in thalassemic patients. The processes are intimately linked such that an ideal therapeutic approach should address all of the complications. Although -thalassemia is one of the first monogenic diseases to be described and represents a global health problem, only recently has the scientific community started to focus on the real molecular mechanisms that underlie this disease, opening new and exciting therapeutic perspectives for thalassemic patients worldwide.

  19. Growth and endocrine disorders in thalassemia: The international network on endocrine complications in thalassemia (I-CET) position statement and guidelines.

    Science.gov (United States)

    De Sanctis, Vincenzo; Soliman, Ashraf T; Elsedfy, Heba; Skordis, Nicos; Kattamis, Christos; Angastiniotis, Michael; Karimi, Mehran; Yassin, Mohd Abdel Daem Mohd; El Awwa, Ahmed; Stoeva, Iva; Raiola, Giuseppe; Galati, Maria Concetta; Bedair, Elsaid M; Fiscina, Bernadette; El Kholy, Mohamed

    2013-01-01

    The current management of thalassemia includes regular transfusion programs and chelation therapy. It is important that physicians be aware that endocrine abnormalities frequently develop mainly in those patients with significant iron overload due to poor compliance to treatment, particularly after the age of 10 years. Since the quality of life of thalassemia patients is a fundamental aim, it is vital to monitor carefully their growth and pubertal development in order to detect abnormalities and to initiate appropriate and early treatment. Abnormalities should be identified and treatment initiated in consultation with a pediatric or an adult endocrinologist and managed accordingly. Appropriate management shall put in consideration many factors such as age, severity of iron overload, presence of chronic liver disease, thrombophilia status, and the presence of psychological problems. All these issues must be discussed by the physician in charge of the patient's care, the endocrinologist and the patient himself. Because any progress in research in the field of early diagnosis and management of growth disorders and endocrine complications in thalassemia should be passed on to and applied adequately to all those suffering from the disease, on the 8 May 2009 in Ferrara, the International Network on Endocrine Complications in Thalassemia (I-CET) was founded in order to transmit the latest information on these disorders to the treating physicians. The I-CET position statement outlined in this document applies to patients with transfusion-dependent thalassemia major to help physicians to anticipate, diagnose, and manage these complications properly.

  20. Growth and endocrine disorders in thalassemia: The international network on endocrine complications in thalassemia (I-CET position statement and guidelines

    Directory of Open Access Journals (Sweden)

    Vincenzo De Sanctis

    2013-01-01

    Full Text Available The current management of thalassemia includes regular transfusion programs and chelation therapy. It is important that physicians be aware that endocrine abnormalities frequently develop mainly in those patients with significant iron overload due to poor compliance to treatment, particularly after the age of 10 years. Since the quality of life of thalassemia patients is a fundamental aim, it is vital to monitor carefully their growth and pubertal development in order to detect abnormalities and to initiate appropriate and early treatment. Abnormalities should be identified and treatment initiated in consultation with a pediatric or an adult endocrinologist and managed accordingly. Appropriate management shall put in consideration many factors such as age, severity of iron overload, presence of chronic liver disease, thrombophilia status, and the presence of psychological problems. All these issues must be discussed by the physician in charge of the patient′s care, the endocrinologist and the patient himself. Because any progress in research in the field of early diagnosis and management of growth disorders and endocrine complications in thalassemia should be passed on to and applied adequately to all those suffering from the disease, on the 8 May 2009 in Ferrara, the International Network on Endocrine Complications in Thalassemia (I-CET was founded in order to transmit the latest information on these disorders to the treating physicians. The I-CET position statement outlined in this document applies to patients with transfusion-dependent thalassemia major to help physicians to anticipate, diagnose, and manage these complications properly.

  1. Development of Gasless Pyrotechnic Cap

    Science.gov (United States)

    1980-05-01

    beam cathode ray oscillo- scope. The caps were ignited by removing the safety pin . This also triggered the oscilloscope. The change in pressure inside...sensitivity. STRIKER SAFETY PIN PERCUSSION CAP FIXED VOLUME / ;PRESSURE TRANSDUCER TO C.R.O. FIG. 8 - Device used to determine pressure time

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

    Science.gov (United States)

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

    2005-01-01

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

  3. Magnetic measurements on human erythrocytes: Normal, beta thalassemia major, and sickle

    Science.gov (United States)

    Sakhnini, Lama

    2003-05-01

    In this article magnetic measurements were made on human erythrocytes at different hemoglobin states (normal and reduced hemoglobin). Different blood samples: normal, beta thalassemia major, and sickle were studied. Beta thalassemia major and sickle samples were taken from patients receiving lifelong blood transfusion treatment. All samples examined exhibited diamagnetic behavior. Beta thalassemia major and sickle samples showed higher diamagnetic susceptibilities than that for the normal, which was attributed to the increase of membrane to hemoglobin volume ratio of the abnormal cells. Magnetic measurements showed that the erythrocytes in the reduced state showed less diamagnetic response in comparison with erythrocytes in the normal state. Analysis of the paramagnetic component of magnetization curves gave an effective magnetic moment of μeff=7.6 μB per reduced hemoglobin molecule. The same procedure was applied to sickle and beta thalassemia major samples and values for μeff were found to be comparable to that of the normal erythrocytes.

  4. Brazilian Thalassemia Association protocol for iron chelation therapy in patients under regular transfusion

    Directory of Open Access Journals (Sweden)

    Monica Pinheiro de Almeida Verissimo

    2013-01-01

    Full Text Available In the absence of an iron chelating agent, patients with beta-thalassemia on regular transfusions present complications of transfusion-related iron overload. Without iron chelation therapy, heart disease is the major cause of death; however, hepatic and endocrine complications also occur. Currently there are three iron chelating agents available for continuous use in patients with thalassemia on regular transfusions (desferrioxamine, deferiprone, and deferasirox providing good results in reducing cardiac, hepatic and endocrine toxicity. These practice guidelines, prepared by the Scientific Committee of Associação Brasileira de Thalassemia (ABRASTA, presents a review of the literature regarding iron overload assessment (by imaging and laboratory exams and the role of T2* magnetic resonance imaging (MRI to control iron overload and iron chelation therapy, with evidence-based recommendations for each clinical situation. Based on this review, the authors propose an iron chelation protocol for patients with thalassemia under regular transfusions.

  5. Prevalence of βS-globin gene haplotypes, α-thalassemia (3.7 kb deletion and redox status in patients with sickle cell anemia in the state of Paraná, Brazil

    Directory of Open Access Journals (Sweden)

    Eliana LitsukoTomimatsu Shimauti

    2015-09-01

    Full Text Available The aim of this study was to determine the frequency of beta S-globin gene (βS globin haplotypes and alpha thalassemia with 3.7 kb deletion (−α3.7kb thalassemia in the northwest region of Paraná state, and to investigate the oxidative and clinical-hematological profile of βS globin carriers in this population. Of the 77 samples analyzed, 17 were Hb SS, 30 were Hb AS and 30 were Hb AA. The βSglobin haplotypes and −α3.7kb thalassemia were identified using polymerase chain reaction.Trolox equivalent antioxidant capacity (TEAC and lipid peroxidation (LPO were assessed spectophotometrically. Serum melatonin levels were determined using high-performance liquid chromatography coupled to coulometric electrochemical detection. The haplotype frequencies in the SS individuals were as follows: Bantu- 21 (62%, Benin - 11 (32% and Atypical- 2 (6%. Bantu/Benin was the most frequent genotype. Of the 47 SS and AS individuals assessed, 17% (n = 8 had the −α3.7kb mutation. Clinical manifestations, as well as serum melatonin, TEAC and LPO levels did not differ between Bantu/Bantu and Bantu/Benin individuals (p > 0.05. Both genotypes were associated with high LPO and TEAC levels and decreased melatonin concentration. These data suggest that the level of oxidative stress in patients with Bantu/Bantu and Bantu/Benin genotypes may overload the antioxidant capacity.

  6. Prevalence of β(S)-globin gene haplotypes, α-thalassemia (3.7 kb deletion) and redox status in patients with sickle cell anemia in the state of Paraná, Brazil.

    Science.gov (United States)

    Shimauti, Eliana LitsukoTomimatsu; Silva, Danilo Grunig Humberto; de Souza, Eniuce Menezes; de Almeida, Eduardo Alves; Leal, Francismar Prestes; Bonini-Domingos, Claudia Regina

    2015-01-01

    The aim of this study was to determine the frequency of beta S-globin gene (β(S) globin) haplotypes and alpha thalassemia with 3.7 kb deletion (-α(3.7kb) thalassemia) in the northwest region of Paraná state, and to investigate the oxidative and clinical-hematological profile of β(S) globin carriers in this population. Of the 77 samples analyzed, 17 were Hb SS, 30 were Hb AS and 30 were Hb AA. The β(S)globin haplotypes and -α(3.7kb) thalassemia were identified using polymerase chain reaction.Trolox equivalent antioxidant capacity (TEAC) and lipid peroxidation (LPO) were assessed spectophotometrically. Serum melatonin levels were determined using high-performance liquid chromatography coupled to coulometric electrochemical detection. The haplotype frequencies in the SS individuals were as follows: Bantu- 21 (62%), Benin - 11 (32%) and Atypical- 2 (6%). Bantu/Benin was the most frequent genotype. Of the 47 SS and AS individuals assessed, 17% (n = 8) had the -α(3.7kb) mutation. Clinical manifestations, as well as serum melatonin, TEAC and LPO levels did not differ between Bantu/Bantu and Bantu/Benin individuals (p > 0.05). Both genotypes were associated with high LPO and TEAC levels and decreased melatonin concentration. These data suggest that the level of oxidative stress in patients with Bantu/Bantu and Bantu/Benin genotypes may overload the antioxidant capacity.

  7. Pyogenic liver abscess in beta-thalassemia major--report of two cases.

    Science.gov (United States)

    Hwang, C F; Lee, C Y; Lee, P I; Chen, J M; Lli, K H; Lin, D T; Chang, M H

    1994-01-01

    Pyogenic liver abscess, which may lead to devastating consequences, is an uncommon medical problem in pediatrics and has generally been reported in compromised hosts. This article describes two patients with beta-thalassemia major and hemochromatosis complicated by Klebsiella pneumoniae liver abscess. One of the patients had severe complications, including subphrenic abscess, pleural effusion and meningitis. To present knowledge, the occurrence of K. pneumoniae liver abscess in patients with beta-thalassemia major has never before been reported in the literature.

  8. Subclinical renal abnormalities in young thalassemia major and intermedia patients and its relation to chelation therapy

    OpenAIRE

    Adly, Amira A.M.; Dalia N. Toaima; Noha Refaat Mohamed; Karim Mahmoud Abu El Seoud

    2014-01-01

    Background: Limited data are available about renal involvement in thalassemia patients. Renal dysfunction in these patients seems to be multifactorial attributed mainly to long standing anemia, chronic hypoxia, iron overload and toxicity of iron chelators. Objective: To assess the frequency of subclinical glomerular and tubular dysfunctions in children and adolescents with β-thalassemia major and intermedia, and to correlate these findings with the degree of iron overload and type of chela...

  9. Sickle-β+ thalassemia with splenic calcification and bone marrow infarction: a case report

    OpenAIRE

    2008-01-01

    We came across an unusual case of a 20 years old male from north India who presented with repeated episodes of pyrexia of unknown origin (PUO) and history of chronic hemolytic anemia. On investigation he was detected to have Sickle-β+ Thalassemia and subtle features of hyposplenism. Radiological investigations revealed extensive splenic calcification and bone marrow examination to evaluate for PUO showed extensive bone marrow infarction and fibrosis. Molecular diagnosis for beta thalassemia m...

  10. Anemia, iron deficiency and thalassemia among adolescents in Northeast Thailand: results from two independent surveys.

    Science.gov (United States)

    Pansuwan, Anupong; Fucharoen, Goonnapa; Fucharoen, Supan; Himakhun, Boonmee; Dangwiboon, Samrit

    2011-01-01

    The prevalence of adolescent anemia, iron deficiency and thalassemia were examined in 2 provinces of northeast Thailand. Blood specimens were collected from adolescent subjects aged 15-17 years in 2 areas; 185 (85 males and 100 females) in Mukdahan province and 313 (116 males and 197 females) in Roi-Et. RBC parameters, serum ferritin levels, Hb and DNA analyses for the identification of common thalassemia genes in Thailand were investigated. The prevalences of anemia were found to be 21.1% (8.1 in male and 13.0 in female) and 16.6% (8.9 in male and 7.7 in female) in Mukdahan and Roi-Et province, respectively. Iron deficiency was observed to be 24.3% in Mukdahan and 14.7% in Roi-Et. Various types of thalassemia were identified in 62.2 and 58.8% of the subject populations, respectively. The proportions of iron deficiency, thalassemia and combined thalassemia and iron deficiency among anemic subjects were 10.2, 53.8 and 30.8% in Mukdahan, and 7.7, 67.3 and 9.6% in Roi-Et. Hematological characteristics were analyzed and are presented. It is concluded that thalassemia and hemoglobinopathies rather than iron deficiency are major causes of adolescent anemia which should be taken into account in public health strategies for the control of anemia in the region.

  11. Association of erythrocyte deformability with red blood cell distribution width in metabolic diseases and thalassemia trait.

    Science.gov (United States)

    Vayá, Amparo; Alis, Rafael; Suescún, Marta; Rivera, Leonor; Murado, Julian; Romagnoli, Marco; Solá, Eva; Hernandez-Mijares, Antonio

    2015-01-01

    Increased red blood distribution width (RDW) in anemia is related to disturbances in the cellular surface/volume ratio, usually accompanied by morphological alterations, while it has been shown in inflammatory diseases that the activity of pro-inflammatory cytokines disturbing erythropoiesis increases RDW. Recently it has been reported that higher RDW is related with decreased erythrocyte deformability, and that it could be related with the association of RDW and increased risk of cardiovascular diseases. In order to analyze the influence of morphological alterations and proinflammatory status on the relationship between RDW and erythrocyte deformability, we analyzed erythrocyte deformability along with RDW and other hematological and biochemical parameters in 36 α-thalassemia, 20 β-thalassemia, 20 δβ-thalassemia trait carriers, 61 metabolic syndrome patients and 76 morbidly obese patients. RDW correlated inversely with erythrocyte deformability in minor β-thalassemia (r =-0.530, p thalassemia is often accompanied by more marked cell-shaped perturbations than other thalassemia traits. This could be the reason for this negative association only in this setting. Higher anisocytosis seems to be associated with greater morphologic alterations (shape/volume), which reduce erythrocyte deformability. The proinflammatory profile in metabolic patients can be related to the positive association of RDW with erythrocyte deformability found in these patients. However, further research is needed to explain the mechanisms underlying this association.

  12. Hypoparathyroidism and intracerebral calcification in patients with beta-thalassemia major

    Energy Technology Data Exchange (ETDEWEB)

    Karimi, M. [Iran-Shiraz-Namazee Hospital, Namazee Square, Hematology Research Center, Department of Pediatrics, Shiraz University of Medical Sciences, Shiraz (Iran, Islamic Republic of)], E-mail: karimim@sums.ac.ir; Rasekhi, A.R. [Iran-Shiraz-Namazee Hospital, Namazee Square, Imaging Research Center, Department of Radiology, Shiraz University of Medical Sciences, Shiraz (Iran, Islamic Republic of)], E-mail: rasekhia@sums.ac.ir; Rasekh, M. [Iran-Shiraz-Namazee Hospital, Namazee Square, Department of Endocrinology and Metabolism, Shiraz University of Medical Sciences, Shiraz (Iran, Islamic Republic of)], E-mail: Rasekhm@sums.ac.ir; Nabavizadeh, S.A. [Iran-Shiraz-Namazee Hospital, Namazee Square, Imaging Research Center, Department of Radiology, Shiraz University of Medical Sciences, Shiraz (Iran, Islamic Republic of)], E-mail: nabavia@gmail.com; Assadsangabi, R. [Iran-Shiraz-Namazee Hospital, Namazee Square, Imaging Research Center, Department of Radiology, Shiraz University of Medical Sciences, Shiraz (Iran, Islamic Republic of)], E-mail: assadsangabi@yahoo.com; Amirhakimi, G.H. [Iran-Shiraz-Namazee Hospital, Namazee Square, Department of Endocrinology and Metabolism, Shiraz University of Medical Sciences, Shiraz (Iran, Islamic Republic of)], E-mail: amirhakimig@sums.ac.ir

    2009-06-15

    Background: Hypoparathyroidism is one of the most important endocrine complications of thalassemia major. This study was conducted to evaluate the prevalence of intracerebral calcifications in patients with thalassemia with and without hypoparathyroidism. Methods: 47 beta-thalassemia patients with hypoparathyroidism underwent a brain CT scan to investigate the presence and extent of intracerebral calcification. 30 age- and sex-matched beta-thalassemic patients with normal parathyroid function who had undergone brain CT for headache, or some other minor neurologic problems were also enrolled in the study serving as controls. The amount of intracerebral calcification, hematologic parameters, and some clinical findings were compared between both groups. Results: Intracerebral calcification was present in 54.2% of beta-thalassemia patients with hypoparathyroidism. The most frequent sites of calcification were basal ganglia, and frontoparietal areas of the brain. Thalami, internal capsule, cerebellum and posterior fossa were other less frequently calcified regions of the brain. In contrast, there was no evidence of intracerebral calcifications in the 30 thalassemic patients with normal parathyroid function. There was not a statistically significant difference between serum ferritin concentrations in thalassemia patient with hypoparathyroidism and those with normal parathyroid function (2781 vs. 2178, P > 0.05). Conclusion: Intracranial calcification is a common finding in thalassemia patients with hypoparathyroidism, it can be extensive and involves most regions of the brain.

  13. Etiopathological mechanisms and clinical characteristics of hyperhemolysis syndrome in Spanish patients with thalassemia.

    Science.gov (United States)

    Vagace, Jose Manuel; Cardesa, Rocío; Corbacho, Antonio; Vázquez, Teresa; de la Maya, Maria Dolores; Gonzalez, Fernando Ataulfo; Nieto, José Bartolomé; Urrutia, Emilia; Gómez, María Jesus; Pascual, Teresa; Aguinaco, Maria Reyes; Gervasini, Guillermo

    2016-09-01

    Hyperhemolysis syndrome (HHS) is characterized by severe intravascular hemolysis with a decrease in the reticulocyte count, which is triggered and aggravated by transfusion and cannot be explained by standard immunohematological studies. A nationwide study was conducted in order to retrospectively identify thalassemia patients with HHS in Spain in order to assess pre-disposing mechanisms for this syndrome. For this, the expression of adhesion (CD49, CD36) and complement-related molecules (C3a, CD59) and the levels of reticulocyte apoptosis and macrophage activation were measured in 4 thalassemia patients with HHS, 14 patients without HHS, and 10 healthy subjects. Five of the six thalassemia patients had δβ-thalassemia. The patients were not alloimmunized prior to the syndrome, which was developed after the first transfusion in all but one case. Patients with δβ-thalassemia did not respond to corticoids or immunoglobulins; only splenectomy was successful. The expression of CD49 (α4β1 integrin) was far higher in patients who had experienced HHS (85.07 ± 18.46 vs. 46.28 ± 24.31; p thalassemia was the most common hemoglobinopathy in patients with HHS. Furthermore, the risk to develop this syndrome may be associated with an increased expression of α4β1 integrin.

  14. Carrier Screening and Prenatal Gene Diagnosis of β-thalassemia by PCR-RDB Technique

    Institute of Scientific and Technical Information of China (English)

    张宏秀; 单可人; 惠春林; 何燕; 袁筑华; 窦友莲; 曾金琳; 谢渊; 修瑾

    2003-01-01

    In order to identify the distribution of gene types of β-thalassemia and reduce the birthrates of β-thalassemia major in Guiyang area, 1054 pregnant women and their spouses from Affiliated Hospital, Guiyang Medical College were screened. The positive samples were analyzed with polymerase chain reaction and reverse dot blot method (PCR-RDB). When both partners were heterozygous identified as carriers for β- thalassemia, the risk of having a fetus who was homozygous or compound heterozygous was 2.66 %; the ratio of male to female was 1/1.15. Seven types of mutation were identified. CD17 and CD41-42 were dominant among them. Among the 4 cases subject to prenatal gene diagnosis, one fetus was completely normal and 3 fetuses were diagnosed as having β-thalassemia major (1 homozygous and 2 compound heterozygous). The fetuses diagnosed as β-thalassemia major were selectively terminated within two weeks. It was concluded that the birthrate of β-thalassemia major in Guiyang area was reduced and the target of improving birth outcome and child development has been achieved.

  15. Thalassemia major and intermedia in jammu and kashmir, India: a regional transfusion centre experience.

    Science.gov (United States)

    Vasudev, Rahul; Sawhney, Vijay

    2014-12-01

    Data on status of thalassemia and hemoglobinopathies from the extreme northern part of India is scarce. We investigated socio-demographic characteristics and management issues related to β-thalassemia in Jammu and Kashmir, India. Data from 96 thalassemia major and intermedia patients visiting the department of transfusion medicine for their transfusion needs was collected. Parameters recorded included age group, age at diagnosis, gender, religion, districts of the state they belonged to, family history of thalassemia, blood group, type of thalassemia (major/intermedia), total number of transfusions received and chelation therapy status. Thalassemia major patients comprised 92 (95.8 %) and intermedia 4 (4.2 %) of the cohort. Most cases were diagnosed in infancy or early childhood. The districts of Jammu and Rajouri together contributed 53 % of the cases. Most patients were Hindu (76/96, 79.2 %). A positive family history was most often obtained from Muslim patients (8/18, 44.4 %). Only 50 % cases were on iron chelation therapy. There is a need to come up with a national/local policy to manage disease in endemic areas and a policy formulated to help families and patients. Data such as ours may help in health management planning for thalassemic patients in this region.

  16. Phenotype and Genotype in a Cohort of 312 Adult Patients with Nontransfusion-Dependent Thalassemia in Northeast Thailand.

    Science.gov (United States)

    Prayalaw, Patcharawadee; Teawtrakul, Nattiya; Jetsrisuparb, Arunee; Pongudom, Saranya; Fucharoen, Goonnapa; Fucharoen, Supan

    2016-01-01

    Patients with nontransfusion-dependent thalassemia (NTDT) do not require regular blood transfusion for survival but may encounter several complications that contribute to morbidity and mortality. We report the molecular heterogeneity and hematological features of NTDT in 312 adult patients in northeast Thailand. Hemoglobin (Hb) and DNA analyses identified 177 subjects with Hb E-β-thalassemia, 1 with homozygous β0-thalassemia and 134 with Hb H, AEBart's and EEBart's diseases. For β-thalassemia, 12 different mutations including both β0- and β+-thalassemias were detected. Coinheritance of α-thalassemia as an ameliorating factor was observed in 18 of 178 cases (10.1%) with β-thalassemia. The α-globin gene triplicated haplotype (αααanti3.7) was observed in 1 case of Hb E-β0-thalassemia. The presence of the -158 (Cx2192;T) Gx03B3;-XmnI polymorphism (+/+) was found to be associated with increased Hb F expression, but its frequency in the studied subjects was low. Those with α-thalassemia included 17 with deletional and 51 nondeletional Hb H, and 63 with AEBart's and 3 with EEBart's diseases. The hematological parameters of these NTDT and genotype-phenotype relationships are presented. The diverse molecular heterogeneity of NTDT underlines the importance of complete genotyping of the patient. These results should prove useful for management planning, the prediction of clinical outcome and to improve genetic counseling for NTDT patients.

  17. Adrenal extramedullary hematopoiesis associated with β-thalassemia major

    Directory of Open Access Journals (Sweden)

    Bijan Keikhaei

    2012-01-01

    Full Text Available The presence of apparently normal hematopoietic tissue outside of bone marrow cavity is defined as extramedullary hema - topoiesis (EMH. EMH is a rare complication in thalassemia major (TM and adrenal gland as well. This report describes a case of adrenal EMH in a 26-year-old man with β-TM. He has been transfused with regular blood transfusion since 9 months. During the routine physical examination he was incidentally found to have a hypoechoic mass at his abdominal ultrasonography. Abdominal computed tomography scan revealed a right well-defined suprarenal mass 7.7¥7.3¥5.8 cm in size. The diagnosis of EMH was confirmed with ultrasonographic-guided fine needle biopsy. Treatment options which include intensified regular blood transfusion and hydroxyurea have been started.

  18. Progress toward the genetic treatment of the beta-thalassemias.

    Science.gov (United States)

    Sadelain, Michel; Lisowski, Leszek; Samakoglu, Selda; Rivella, Stefano; May, Chad; Riviere, Isabelle

    2005-01-01

    The beta-thalassemias are congenital anemias that are caused by mutations that reduce or abolish expression of the beta-globin gene. They can be cured by allogeneic hematopoietic stem cell (HSC) transplantation, but this therapeutic option is not available to most patients. The transfer of a regulated beta-globin gene in autologous HSCs is a highly attractive alternative treatment. This strategy, which is simple in principle, raises major challenges in terms of controlling expression of the globin transgene, which ideally should be erythroid specific, differentiation- and stage-restricted, elevated, position independent, and sustained over time. Using lentiviral vectors, May et al. demonstrated in 2000 that an optimized combination of proximal and distal transcriptional control elements permits lineage-specific and elevated beta-globin expression, resulting in therapeutic hemoglobin production and correction of anemia in beta-thalassemic mice. Several groups have by now replicated and extended these findings to various mouse models of severe hemoglobinopathies, thus fueling enthusiasm for a potential treatment of beta-thalassemia based on globin gene transfer. Current investigation focuses on safety issues and the need for improved vector production methodologies. The safe implementation of stem cell-based gene therapy requires the prevention of the formation of replication-competent viral genomes and minimization of the risk of insertional oncogenesis. Importantly, globin vectors, in which transcriptional activity is highly restricted, have a lesser risk of activating oncogenes in hematopoietic progenitors than non-tissue-specific vectors, by virtue of their late-stage erythroid specificity. As such, they provide a general paradigm for improving vector safety in stem cell-based gene therapy.

  19. Psychometric properties of the Specific Thalassemia Quality of Life Instrument for adults

    Directory of Open Access Journals (Sweden)

    Lyrakos GN

    2012-07-01

    Full Text Available Georgios N Lyrakos,1,2 Demetra Vini,2 Helen Aslani,2 Marouso Drosou-Servou212nd Department of Anesthesiology, School of Medicine, University of Athens, Pain Clinic, Attikon University Hospital, 2Thalassemia Unit, General Hospital of Nikaia Ag. Panteleimon, Athens, GreeceBackground: No specific questionnaire has been developed to assess the health-related quality of life of thalassemia patients. Thus, the main objective of this study was to develop, according to psychometric standards, a self-administered Specific Thalassemia Quality of Life Instrument (STQOLI for adult patients.Methods: First, a qualitative phase was conducted to generate items and identify domains using the critical analysis incident technique and a literature review. A list of easily comprehensible, non-redundant items was defined using the Delphi technique and a pilot study on ten thalassemia patients. This phase involved both patients and experts. The second step was a quantitative validation phase comprising a study of 128 thalassemia patients in a single hospital. It was designed to select items, identify dimensions, and measure reliability and internal and concurrent validity. The psychometric and scaling properties of the proposed 41-item Specific Thalassemia Quality of Life Instrument were then assessed among patients recruited from the Thalassemia Unit at the General Hospital of Nikaia, Greece.Results: The final questionnaire had 41 items comprising four main domains and one global item about general health. The factorial structure was satisfactory (loading > 0.40 on each factor of the four domains for all items. Interscale correlations ranged from 0.06 to 0.78, Cronbach's α-coefficients were 0.78 for the psychosocial domain, 0.77 for the chelation domain, 0.72 for the transfusion domain, 0.81 for the disease and symptoms domain, and 0.840 for the total score of the questionnaire.Conclusion: The 41-item Specific Thalassemia Quality of Life Instrument seems to be a

  20. ATLAS - End-Cap calorimeter

    CERN Multimedia

    2006-01-01

    The End-cap calorimeter was moved with the help of the rails and this calorimeter will measure the energy of particles close to the beam axis when protons collide. Cooling is important for maximum detector efficiency.

  1. Molecular Mechanism of AHSP-Mediated Stabilization of Alpha-Hemoglobin

    Energy Technology Data Exchange (ETDEWEB)

    Feng,L.; Gell, D.; Zhou, S.; Gu, L.; Kong, Y.; Li, J.; Hu, M.; Yan, N.; Lee, C.; et al.

    2005-01-01

    Hemoglobin A (HbA), the oxygen delivery system in humans, comprises two alpha and two beta subunits. Free alpha-hemoglobin (alphaHb) is unstable, and its precipitation contributes to the pathophysiology of beta thalassemia. In erythrocytes, the alpha-hemoglobin stabilizing protein (AHSP) binds alphaHb and inhibits its precipitation. The crystal structure of AHSP bound to Fe(II)-alphaHb reveals that AHSP specifically recognizes the G and H helices of alphaHb through a hydrophobic interface that largely recapitulates the alpha1-beta1 interface of hemoglobin. The AHSP-alphaHb interactions are extensive but suboptimal, explaining why beta-hemoglobin can competitively displace AHSP to form HbA. Remarkably, the Fe(II)-heme group in AHSP bound alphaHb is coordinated by the distal but not the proximal histidine. Importantly, binding to AHSP facilitates the conversion of oxy-alphaHb to a deoxygenated, oxidized [Fe(III)], nonreactive form in which all six coordinate positions are occupied. These observations reveal the molecular mechanisms by which AHSP stabilizes free alphaHb.

  2. Risk of erectile dysfunction in transfusion-naive thalassemia men: a nationwide population-based retrospective cohort study.

    Science.gov (United States)

    Chen, Yu-Guang; Lin, Te-Yu; Lin, Cheng-Li; Dai, Ming-Shen; Ho, Ching-Liang; Kao, Chia-Hung

    2015-04-01

    Based on the mechanism of pathophysiology, thalassemia major or transfusion-dependent thalassemia patients may have an increased risk of developing organic erectile dysfunction resulting from hypogonadism. However, there have been few studies investigating the association between erectile dysfunction and transfusion-naive thalassemia populations. We constructed a population-based cohort study to elucidate the association between transfusion-naive thalassemia populations and organic erectile dysfunction. This nationwide population-based cohort study involved analyzing data from 1998 to 2010 obtained from the Taiwanese National Health Insurance Research Database, with a follow-up period extending to the end of 2011. We identified men with transfusion-naive thalassemia and selected a comparison cohort that was frequency-matched with these according to age, and year of diagnosis thalassemia at a ratio of 1 thalassemia man to 4 control men. We analyzed the risks for transfusion-naive thalassemia men and organic erectile dysfunction by using Cox proportional hazards regression models. In this study, 588 transfusion-naive thalassemia men and 2337 controls were included. Total 12 patients were identified within the thalassaemia group and 10 within the control group. The overall risks for developing organic erectile dysfunction were 4.56-fold in patients with transfusion-naive thalassemia men compared with the comparison cohort after we adjusted for age and comorbidities. Our long-term cohort study results showed that in transfusion-naive thalassemia men, there was a higher risk for the development of organic erectile dysfunction, particularly in those patients with comorbidities.

  3. Prenatal diagnosis of thalassemia and hemoglobinopathies in Thailand: experience from 100 pregnancies.

    Science.gov (United States)

    Fucharoen, S; Winichagoon, P; Thonglairoam, V; Siriboon, W; Siritanaratkul, N; Kanokpongsakdi, S; Vantanasiri, C

    1991-03-01

    In this review, we describe a simple strategy to detect the three severe thalassemic diseases commonly found in Thailand. Hb Bart's hydrops fetalis can be detected unambiguously by ultrasonography at 18-20 weeks of gestation or detected early in the first trimester by the gene amplification technique. Prenatal diagnosis for homozygous beta-thalassemia is better performed in the second trimester by in vitro protein synthesis. This is because the molecular defects of some beta-thalassemias are still unknown and homozygosity of the same mutation is low. In contrast, beta-thalassemia/Hb E is easily detected, in the first trimester, by direct visualization on electrophoresis or by dot blot analysis of enzymatically amplified DNA with a set of nonradioactively labeled oligonucleotide probes complementary to the most common mutations. We also found that the beta/gamma synthesis ratio in homozygous Hb E is similar to that of beta-thalassemia/Hb E and DNA analysis is the only method to distinguish these two conditions in the couple at risk of having either beta-thalassemia/Hb E or asymptomatic homozygous Hb E. In 100 pregnancies studied, the diagnoses were achieved in 96 pregnancies. Complications leading to fetal loss were found in 3 pregnancies: one woman developed amnionitis after fetal blood sampling; one had amniotic fluid leakage after the biopsy, and the third, carrying a normal fetus, aborted 10 days after fetal blood sampling with urinary tract infection and high fever. However, these figures are compatible with other reports and the risks are significantly lower than that of thalassemic disease the fetus is facing. One case of beta-thalassemia/Hb E was incorrectly diagnosed prenatally as being Hb E trait. In twenty-five pregnancies (25%) prenatally diagnosed to carry affected fetuses it was decided to have abortion. This study shows the feasibility of prenatal diagnosis for thalassemic diseases in Thailand which, in addition to screening and genetic counseling

  4. Screening of β-thalassemia trait and other hemoglobinopathies among blood donors in Punjab

    Directory of Open Access Journals (Sweden)

    Rajesh Kumar

    2015-01-01

    Full Text Available Introduction: Hemoglobinopathies are common genetic disorders of hemoglobin, which can be prevented by population screening and offering genetic counseling. The cumulative gene frequency of hemoglobinopathies in India is 4.2%. The carrier state for β-thalassemia in India varies from 1% to 17% with an average of 3.2%. The present study was undertaken to find out the burden of hemoglobinopathies and spectrum of this disorders among the blood donors. Materials and Methods: The study includes 975 students between 18 and 25 years who donated blood, were screened for β-thalassemia trait and related hemoglobinopathies by high-performance liquid chromatography (HPLC using Bio-Rad variant. Samples were also run on a hemato analyzer for red cell indices and peripheral smear for red cell morphology. Results: A total of 41 donors showed abnormal hemoglobin fractions in HPLC. Out of these, 32 (3.3% were diagnosed with β-thalassemia trait, 8 (0.8% with Hb-D Punjab and 1 (0.1% with Hb-S trait. The frequency of β-thalassemia trait in the student from different geographical regions varied from 0.8% to 4.44%, being the highest in those from Punjab and frequency of β-thalassemia trait in different caste groups varied from 0 to 4.74%, being the highest in the student from Jatt Sikh community. Conclusions: A universal approach of screening for β-thalassemia trait should be included as a part of standard blood testing among the college students, premarital and of the extended family of thalassemics. Population group with high gene frequencies requires screening programs as well as increased awareness and education program to control the birth of thalassemia major.

  5. Evaluation of Tricuspid Regurgitant Jet Velocity in Thalassemia Patients with Splenectomy

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    Nikparvar

    2015-02-01

    Full Text Available Background β-thalassemia is an inherited disorder of β-globin biosynthesis. Dysfunction in hemoglobin chain production, ineffective erythropoiesis, and hemolysis occur in β-thalassemia. Pulmonary arterial hypertension (PAH is increasingly detected in patients with β-thalassemia, and splenectomy which decreases the need for blood transfusion increases the pulmonary artery pressure (PAP. Objectives This study aimed to assess the PAP in patients with β-thalassemia (male or female and major or intermedia who had undergone splenectomy. Methods A total of 137 patients suffering from β-thalassemia were evaluated during the study. All subjects were referred for cardiac evaluation. Clinical history, presence of cardiac symptoms, and previous splenectomy were noted. Standard M-mode, 2D, and Doppler echocardiographic examinations were performed for all subjects. Patients with a tricuspid regurgitant jet velocity (TRV ≥ 2.5 m/s were considered at risk for PAH. Results Average age of the patients was 21.15 ± 6.68 years. No significant difference was observed in the PAP between the 2 groups of thalassemia major and intermedia and also the 2 sex groups. Indeed, 6.6% of the patients had an increased PAP. The significant finding of the study was that the patients who had had splenectomy were significantly at an increased risk of PAH (P = 0.046. Conclusions The etiology of PAH in thalassemia is multifactorial such as inflammatory mediators. Also, the absence of the spleen plays an important role in developing a high TRV and PAH.

  6. Genetic therapy for beta-thalassemia: from the bench to the bedside.

    Science.gov (United States)

    Arumugam, Paritha; Malik, Punam

    2010-01-01

    Beta-thalassemia is a genetic disorder with mutations in the β-globin gene that reduce or abolish β-globin protein production. Patients with β-thalassemia major (Cooley's anemia) become severely anemic by 6 to 18 months of age, and are transfusion dependent for life, while those with thalassemia intermedia, a less-severe form of thalassemia, are intermittently or rarely transfused. An allogeneically matched bone marrow transplant is curative, although it is restricted to those with matched donors. Gene therapy holds the promise of "fixing" one's own bone marrow cells by transferring the normal β-globin or γ-globin gene into hematopoietic stem cells (HSCs) to permanently produce normal red blood cells. Requirements for effective gene transfer for the treatment of β-thalassemia are regulated, erythroid-specific, consistent, and high-level β-globin or γ-globin expression. Gamma retroviral vectors have had great success with immune-deficiency disorders, but due to vector-associated limitations, they have limited utility in hemoglobinopathies. Lentivirus vectors, on the other hand, have now been shown in several studies to correct mouse and animal models of thalassemia. The immediate challenges of the field as it moves toward clinical trials are to optimize gene transfer and engraftment of a high proportion of genetically modified HSCs and to minimize the adverse consequences that can result from random integration of vectors into the genome by improving current vector design or developing novel vectors. This article discusses the current state of the art in gene therapy for β-thalassemia and some of the challenges it faces in human trials.

  7. Alpha fetoprotein

    Science.gov (United States)

    Fetal alpha globulin; AFP ... Greater than normal levels of AFP may be due to: Cancer in testes , ovaries, biliary (liver secretion) tract, stomach, or pancreas Cirrhosis of the liver Liver cancer ...

  8. Comparison of human CAP and CAP2, homologs of the yeast adenylyl cyclase-associated proteins.

    Science.gov (United States)

    Yu, G; Swiston, J; Young, D

    1994-06-01

    We previously reported the identification of human CAP, a protein that is related to the Saccharomyces cerevisiae and Schizosaccharomyces pombe adenylyl cyclase-associated CAP proteins. The two yeast CAP proteins have similar functions: the N-terminal domains are required for the normal function of adenylyl cyclase, while loss of the C-terminal domains result in morphological and nutritional defects that are unrelated to the cAMP pathways. We have amplified and cloned cDNAs from a human glioblastoma library that encode a second CAP-related protein, CAP2. The human CAP and CAP2 proteins are 64% identical. Expression of either human CAP or CAP2 in S. cerevisiae cap- strains suppresses phenotypes associated with deletion of the C-terminal domain of CAP, but does not restore hyper-activation of adenylyl cyclase by RAS2val19. Similarly, expression of either human CAP or CAP2 in S. pombe cap- strains suppresses the morphological and temperature-sensitive phenotypes associated with deletion of the C-terminal domain of CAP in this yeast. In addition, expression of human CAP, but not CAP2, suppresses the propensity to sporulate due to deletion of the N-terminal domain of CAP in S. pombe. This latter observation suggests that human CAP restores normal adenylyl cyclase activity in S. pombe cap- cells. Thus, functional properties of both N-terminal and C-terminal domains are conserved between the human and S. pombe CAP proteins.

  9. Prevalence of transfusion transmitted infections amongst multiple blood transfused patients of β-thalassemia major in a tertiary care hospital

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    Kundan Mittal

    2016-12-01

    Conclusions: Thalassemia is a chronic transfusion dependent disease complicated by the effects of iron overload on various organs leading to increased morbidity and mortality. The risk of transmission of TTI in thalassemia increases with time as number of transfusions increase. Use of advanced technology in blood screening, voluntary donations, donor selection, asepsis during blood transfusion should be used to curtail the transmission.

  10. a+- Thalassemia Protects against Anemia Associated with Asymptomatic Malaria: Evidence from Community-Based Surveys in Tanzania and Kenya

    NARCIS (Netherlands)

    Veenemans, J.; Andang'o, P.E.A.; Mbugi, E.V.; Kraaijenhagen, R.; Mwaniki, D.; Mockenhaupt, F.P.; Roewer, S.; Olomi, R.M.; Shao, J.F.; Meer, van der J.W.M.; Savelkoul, H.F.J.; Verhoef, J.C.M.

    2008-01-01

    Background. In hospital-based studies, ¿+-thalassemia has been found to protect against severe, life-threatening falciparum malaria. ¿+-Thalassemia does not seem to prevent infection or high parasite densities but rather limits progression to severe disease¿in particular, severe malarial anemia. We

  11. 地中海贫血胸部髓外造血影像表现(附6例分析)%Imaging findings of intrathoracic extramedullary hematopoiesis in thalassemia:sixe cases report

    Institute of Scientific and Technical Information of China (English)

    杨军克; 黄筠洋; 俞雷; 岑炳奎; 黄晓

    2012-01-01

    目的 探讨地中海贫血胸部髓外造血组织增生的影像表现,提高影像诊断和鉴别诊断.方法 回顾性分析经临床证实的6例地中海贫血继发髓外造血(EMH)的胸部影像学资料,β-地中海贫血5例,α-地中海贫血1例.胸部X线平片6例,CT平扫4例,MRI平扫及增强2例.结果 影像表现为两侧脊柱旁瘤样软组织肿块影,4例合并胸壁肋骨下EMH,1例合并胸壁肋骨下、肺部及胸段椎管内多部位EMH;2例β-地中海贫血EMH见纤细骨针样钙化,MRI上呈等T1等T2信号,轻-中度强化;1例α-地中海贫血EMH巨大,密度不均,T1、T2呈等、高信号,轻-中度不均匀强化,2年后X线平片观察EMH大小有变化.CT引导下穿刺活检,镜下大部分为脂肪组织,并见片状坏死灶.结论 地中海贫血继发EMH,依据影像表现特点,结合临床及实验室检查可做出正确诊断.%Objective To investigate the imaging findings of intrathoracic extramedullary hematopoiesis(EMH) in thalassemia,so that to improve its diagnosis and differential diagnosis.Methods Clinical and imaging findings of 6 cases with EMH in thalassemia were retrospectively analyzed.There were Beta-thalassemia in 5 cases and Alpha-thalassemia in 1 case; 6 cases were examined by chest X-ray,CT plain scans in A cases, MRI plain scan and contrast-enhanced scan in 2 cases were performed.Results The imaging features of EMH were tumor-like masses at the posterior mediastinum of bilateral paravertebral, and accompanied with chest wall EMH in 4 cases,chest wall,lung and spinal canal EMH in 1 case.The calcific shadows of bony trabecula-like inside the masses were seen in 2 cases with Beta-thalassemia, and on MRI, EMH were of same signal intensity as compared to adjacent muscles on T1WI and T2WI,and slight to mild homogeneous enhancement after intravenous contrast administration.1 case with Alpha-thalassemia, the signal intensity or density of the lesions was inhomogeneous,and isointense and high signal

  12. Rare association between two genetic conditions: turner syndrome and beta thalassemia minor

    Directory of Open Access Journals (Sweden)

    Dorina STOICANESCU

    2009-11-01

    Full Text Available Rare disorders are defined as diseases, including those of genetic origin, which are life-threatening or chronically debilitating, which are of such low prevalence that special combined efforts are needed to address them. We present a case with a rare association between two genetic conditions: Turner phenotype and beta thalassemia minor. Turner syndrome is a chromosomal disorder that is characterized by the absence of all or part of a second sex chromosome in some or all cells. This condition occurs in 1 in 2,500 to 3,000 girls. The physical features include webbing of the neck, short stature, delayed growth of the skeleton, broad chest, cardivascular abnormalities and gonadal dysgenesis. Women with this disorder are usually infertile due to ovarian failure. The clinical diagnosis was confirmed by the cytogenetic and by FISH analysis, which revealed the presence of only one X chromosome. Treatment may include human growth hormone and estrogen replacement therapy. On the other hand, thalassemias are genetic conditions that result from imbalance in the normal coordinated synthesis of the globin subunits that make up the hemoglobin tetramer, leading to decreased and defective production of hemoglobin. Beta thalassemia syndromes are hereditary disorders characterized by a genetic deficiency in the synthesis of beta-globin chains. Beta thalassemia is inherited in an autosomal recessive manner. Thalassemia minor usually presents as an asymptomatic mild microcytic anemia, but our case also had splenomegaly and required splenectomy.

  13. Investigation of molecular heterogeneity of β-thalassemia disorder in District Charsadda of Pakistan

    Science.gov (United States)

    Shakeel, Muhammad; Arif, Muhammad; Rehman, Shoaib Ur; Yaseen, Tabassum

    2016-01-01

    Objective: Thalassemia is blood related disease which arises from the reduced level of hemoglobin in red blood cells (RBC), a protein responsible for carrying oxygen inside the body. Considering its widespread occurrence in developing countries like Pakistan, this study aims to investigate the common molecular anomalies of the beta thalassemia disease in district Charsadda, Khyber Pakhtunkhwa. Methods: This work was done at Abdul Wali Khan University (AWKU) Mardan, Khyber Pakhtunkhwa, Pakistan. The work was performed on the blood samples collected from the patients and their families with beta thalassemia major (n = 13 families) belonged to District Charsadda. The collected blood samples were analyzed for presence of six known mutations with the help of polymerase cha in reaction technique i.e. amplification of refractory mutation system. Results: Our Study reports six known mutations (IVS-1-5, FSC 8/9, CD 41/42, IVS-1-1, CD 15 and FSC-5) accounting for about 90% of total beta thalassemia genes in this country. Among the reported mutations, IVS 1-5 was the most prevalent beta thalassemia gene in patients belonging to District Charsadda. Conclusion: The results and findings of the current study may help in accessing the frequency of these common mutations and in initiating pre-natal diagnosis programme in Pakistan. PMID:27182268

  14. β-thalassemia: a model for elucidating the dynamic regulation of ineffective erythropoiesis and iron metabolism.

    Science.gov (United States)

    Ginzburg, Yelena; Rivella, Stefano

    2011-10-20

    β-thalassemia is a disease characterized by anemia and is associated with ineffective erythropoiesis and iron dysregulation resulting in iron overload. The peptide hormone hepcidin regulates iron metabolism, and insufficient hepcidin synthesis is responsible for iron overload in minimally transfused patients with this disease. Understanding the crosstalk between erythropoiesis and iron metabolism is an area of active investigation in which patients with and models of β-thalassemia have provided significant insight. The dependence of erythropoiesis on iron presupposes that iron demand for hemoglobin synthesis is involved in the regulation of iron metabolism. Major advances have been made in understanding iron availability for erythropoiesis and its dysregulation in β-thalassemia. In this review, we describe the clinical characteristics and current therapeutic standard in β-thalassemia, explore the definition of ineffective erythropoiesis, and discuss its role in hepcidin regulation. In preclinical experiments using interventions such as transferrin, hepcidin agonists, and JAK2 inhibitors, we provide evidence of potential new treatment alternatives that elucidate mechanisms by which expanded or ineffective erythropoiesis may regulate iron supply, distribution, and utilization in diseases such as β-thalassemia.

  15. Oxidative stress and age-related changes in T cells: is thalassemia a model of accelerated immune system aging?

    Science.gov (United States)

    Ghatreh-Samani, Mahdi; Esmaeili, Nafiseh; Soleimani, Masoud; Asadi-Samani, Majid; Ghatreh-Samani, Keihan; Shirzad, Hedayatolah

    2016-01-01

    Iron overload in β-thalassemia major occurs mainly due to blood transfusion, an essential treatment for β-thalassemia major patients, which results in oxidative stress. It has been thought that oxidative stress causes elevation of immune system senescent cells. Under this condition, cells normally enhance in aging, which is referred to as premature immunosenescence. Because there is no animal model for immunosenescence, most knowledge on the immunosenescence pattern is based on induction of immunosenescence. In this review, we describe iron overload and oxidative stress in β-thalassemia major patients and how they make these patients a suitable human model for immunosenescence. We also consider oxidative stress in some kinds of chronic virus infections, which induce changes in the immune system similar to β-thalassemia major. In conclusion, a therapeutic approach used to improve the immune system in such chronic virus diseases, may change the immunosenescence state and make life conditions better for β-thalassemia major patients.

  16. Cardiac failure in β-thalassemia: diagnosis, prevention and management

    Directory of Open Access Journals (Sweden)

    A. Aessopos

    2011-12-01

    Full Text Available Heart failure always represented and still remains the leading cause of mortality in β (β-thalassemia, despite the therapeutic advances and the considerable amelioration of prognosis accomplished over the last decades. High cardiac output due to chronic anemia and myocardial iron overload due to repetitive blood transfusions are the two main pathogenetic mechanisms causing heart failure in β-thalassemia. In regularly treated thalassemia major patients, left ventricular dysfunction, resulting mainly from myocardial siderosis, is considered to be the primary cause of heart failure and thus the prevention, early recognition and effective management of iron overload is of key importance. However, the spectrum of cardiovascular complications that may ultimately lead to heart is wide and should be individually investigated in each one of the patients. Echocardiography is the main modality used for the regular follow-up and screening of asymptomatic patients and for the evaluation of patients with cardiac symptoms, while the T2* relaxation time provided by magnetic resonance imaging allows the accurate identification and quantification of myocardial iron burden and thus the proper guidance of iron chelation therapy. 近几十年来,尽管治疗方法取得进步和预断方法得到显著改进,但是心脏衰竭仍是引起β地中海贫血症患者死亡的主要原因。 慢性贫血导致的高心输出量和反复输血导致的心脏铁过载,是导致β地中海贫血患者心脏衰竭的两大发病机制。 在常规治疗的重型地中海贫血患者中,心脏铁质沉着病引起的可逆性左心室功能障碍,被认为是心脏衰竭的主要原因。因此,预防、早期确诊和有效控制铁过载至关重要。 然而,最终导致心脏衰竭的心血管并发症的症状繁多,应对每个患者单独进行检查。 超声心动图仪是用于无症状患者定期随访、筛查和诊断有心脏病症状患

  17. The North Zealand CAP Monitor

    DEFF Research Database (Denmark)

    Nielsen, Minna; Ravn, Pernille; Notander Clausen, Lise

    Contect We describe how we developed a monitoring system for community acquired pneumonia (CAP) at North Zealand Regional hospital. We serve 310.000 inhabitants and annually around 3200 patients with CAP are admitted. As part of a program of clinical pathways for common conditions, a pathway...... for pneumonia was designed and implemented in 2010. Problem In spite of our clinical pathway for CAP we found delays in start of treatment, overuse of antibiotics and long length of stay (LOS). Mortality was nearly 20 %. Assessment of problem and analysis of its causes We established an audit group of two...... nurses and two senior doctors. Direct observations of the clinical processes revealed problems of coordination, complex disease trajectories that did not fit with the pneumonia pathway, unclear guidelines and variation in their interpretation. Intervention We designed a measurement system to monitor...

  18. Macrophages support pathological erythropoiesis in polycythemia vera and β-thalassemia.

    Science.gov (United States)

    Ramos, Pedro; Casu, Carla; Gardenghi, Sara; Breda, Laura; Crielaard, Bart J; Guy, Ella; Marongiu, Maria Franca; Gupta, Ritama; Levine, Ross L; Abdel-Wahab, Omar; Ebert, Benjamin L; Van Rooijen, Nico; Ghaffari, Saghi; Grady, Robert W; Giardina, Patricia J; Rivella, Stefano

    2013-04-01

    Regulation of erythropoiesis is achieved by the integration of distinct signals. Among them, macrophages are emerging as erythropoietin-complementary regulators of erythroid development, particularly under stress conditions. We investigated the contribution of macrophages to physiological and pathological conditions of enhanced erythropoiesis. We used mouse models of induced anemia, polycythemia vera and β-thalassemia in which macrophages were chemically depleted. Our data indicate that macrophages contribute decisively to recovery from induced anemia, as well as the pathological progression of polycythemia vera and β-thalassemia, by modulating erythroid proliferation and differentiation. We validated these observations in primary human cultures, showing a direct impact of macrophages on the proliferation and enucleation of erythroblasts from healthy individuals and patients with polycythemia vera or β-thalassemia. The contribution of macrophages to stress and pathological erythropoiesis, which we have termed stress erythropoiesis macrophage-supporting activity, may have therapeutic implications.

  19. Combining gene therapy and fetal hemoglobin induction for treatment of β-thalassemia.

    Science.gov (United States)

    Breda, Laura; Rivella, Stefano; Zuccato, Cristina; Gambari, Roberto

    2013-06-01

    β-thalassemias are caused by nearly 300 mutations of the β-globin gene, leading to a low or absent production of adult hemoglobin (HbA). Two major therapeutic approaches have recently been proposed: gene therapy and induction of fetal hemoglobin (HbF) with the objective of achieving clinically relevant levels of Hbs. The objective of this article is to describe the development of therapeutic strategies based on a combination of gene therapy and induction of HbFs. An increase of β-globin gene expression in β-thalassemia cells can be achieved by gene therapy, although de novo production of clinically relevant levels of adult Hb may be difficult to obtain. On the other hand, an increased production of HbF is beneficial in β-thalassemia. The combination of gene therapy and HbF induction appears to be a pertinent strategy to achieve clinically relevant results.

  20. Levels of Beta-2 Microglobulin and Cystatin C in Beta Thalassemia Major Patients

    Directory of Open Access Journals (Sweden)

    Ayse Kacar

    2014-03-01

    Full Text Available Aim: Thalassemia is accepted to be the most common genetic disease in the world. This study was performed to establish whether there was a glomerular renal damage, which was usually a less mentioned subject in patients with Beta Thalassemia Major, and to compare urea, creatinine and creatinine clearance with early indicators of kidney damage as Cystatin-C and %u03B2-2 microglobulin as on determining the glomerular damage. Material and Method: This study was prospectively performed in patients, who were regularly followed in the children hematology outpatient clinic with a diagnosis of Beta Thalassemia Major. Results: There was no statistically significant difference between urea and levels of creatinine clearance and Cystatin-C. There was a statistically negative relationship between creatinine and creatinine clearance at an advanced level as 53.7% (p: 0.002, p

  1. Proposed low-cost premarital screening program for prevention of sickle cell and thalassemia in Yemen.

    Science.gov (United States)

    Al-Nood, Hafiz; Al-Hadi, Abdulrahman

    2013-01-01

    In Yemen, the prevalence of sickle cell trait and β-thalassemia trait are high. The aim of this premarital program is to identify sickle cell and thalassemia carrier couples in Yemen before completing marriages proposal, in order to prevent affected birth. This can be achieved by applying a low-cost premarital screening program using simple blood tests compatible with the limited health resources of the country. If microcytosis or positive sickle cell is found in both or one partner has microcytosis and the other has positive sickle cell, so their children at high risk of having sickle cell or/and thalassemia diseases. Carrier couples will be referred to genetic counseling. The outcomes of this preventive program are predicted to decrease the incidence of affected birth and reduce the health burden of these disorders. The success of this program also requires governmental, educational and religious supports.

  2. Proposed low-cost premarital screening program for prevention of sickle cell and thalassemia in Yemen

    Science.gov (United States)

    Al-Nood, Hafiz; Al-Hadi, Abdulrahman

    2013-01-01

    In Yemen, the prevalence of sickle cell trait and β-thalassemia trait are high. The aim of this premarital program is to identify sickle cell and thalassemia carrier couples in Yemen before completing marriages proposal, in order to prevent affected birth. This can be achieved by applying a low-cost premarital screening program using simple blood tests compatible with the limited health resources of the country. If microcytosis or positive sickle cell is found in both or one partner has microcytosis and the other has positive sickle cell, so their children at high risk of having sickle cell or/and thalassemia diseases. Carrier couples will be referred to genetic counseling. The outcomes of this preventive program are predicted to decrease the incidence of affected birth and reduce the health burden of these disorders. The success of this program also requires governmental, educational and religious supports. PMID:25003062

  3. Iron chelation therapy in transfusion-dependent thalassemia patients: current strategies and future directions

    Directory of Open Access Journals (Sweden)

    Saliba AN

    2015-06-01

    Full Text Available Antoine N Saliba, Afif R Harb, Ali T Taher Department of Internal Medicine, Division of Hematology/Oncology, American University of Beirut, Beirut, Lebanon Abstract: Transfusional iron overload is a major target in the care of patients with transfusion-dependent thalassemia (TDT and other refractory anemias. Iron accumulates in the liver, heart, and endocrine organs leading to a wide array of complications. In this review, we summarize the characteristics of the approved iron chelators, deferoxamine, deferiprone, and deferasirox, and the evidence behind the use of each, as monotherapy or as part of combination therapy. We also review the different guidelines on iron chelation in TDT. This review also discusses future prospects and directions in the treatment of transfusional iron overload in TDT whether through innovation in chelation or other therapies, such as novel agents that improve transfusion dependence. Keywords: thalassemia, transfusion-dependent thalassemia, iron overload, iron chelation therapy, transfusion

  4. $\\alpha_s$ review (2016)

    CERN Document Server

    d'Enterria, David

    2016-01-01

    The current world-average of the strong coupling at the Z pole mass, $\\alpha_s(m^2_{Z}) = 0.1181 \\pm 0.0013$, is obtained from a comparison of perturbative QCD calculations computed, at least, at next-to-next-to-leading-order accuracy, to a set of 6 groups of experimental observables: (i) lattice QCD "data", (ii) $\\tau$ hadronic decays, (iii) proton structure functions, (iv) event shapes and jet rates in $e^+e^-$ collisions, (v) Z boson hadronic decays, and (vi) top-quark cross sections in p-p collisions. In addition, at least 8 other $\\alpha_s$ extractions, usually with a lower level of theoretical and/or experimental precision today, have been proposed: pion, $\\Upsilon$, W hadronic decays; soft and hard fragmentation functions; jets cross sections in pp, e-p and $\\gamma$-p collisions; and photon F$_2$ structure function in $\\gamma\\,\\gamma$ collisions. These 14 $\\alpha_s$ determinations are reviewed, and the perspectives of reduction of their present uncertainties are discussed.

  5. Phosphoproteomic analysis of apoptotic hematopoietic stem cells from hemoglobin E/β-thalassemia

    Directory of Open Access Journals (Sweden)

    Roytrakul Sittiruk

    2011-06-01

    Full Text Available Abstract Background Hemoglobin E/β-thalassemia is particularly common in Southeast Asia and has variable symptoms ranging from mild to severe anemia. Previous investigations demonstrated the remarkable symptoms of β-thalassemia in terms of the acceleration of apoptotic cell death. Ineffective erythropoiesis has been studied in human hematopoietic stem cells, however the distinct apoptotic mechanism was unclear. Methods The phosphoproteome of bone marrow HSCs/CD34+ cells from HbE/β-thalassemic patients was analyzed using IMAC phosphoprotein isolation followed by LC-MS/MS detection. Decyder MS software was used to quantitate differentially expressed proteins in 3 patients and 2 normal donors. The differentially expressed proteins from HSCs/CD34+ cells were compared with HbE/β-thalassemia and normal HSCs. Results A significant change in abundance of 229 phosphoproteins was demonstrated. Importantly, the analysis of the candidate proteins revealed a high abundance of proteins that are commonly found in apoptotic cells including cytochrome C, caspase 6 and apoptosis inducing factors. Moreover, in the HSCs patients a significant increase was observed in a specific type of phosphoserine/threonine binding protein, which is known to act as an important signal mediator for the regulation of cell survival and apoptosis in HbE/β-thalassemia. Conclusions Our study used a novel method to investigate proteins that influence a particular pathway in a given disease or physiological condition. Ultimately, phosphoproteome profiling in HbE/β-thalassemic stem cells is an effective method to further investigate the cell death mechanism of ineffective erythropoiesis in β-thalassemia. Our report provides a comprehensive phosphoproteome, an important resource for the study of ineffective erythropoiesis and developing therapies for HbE/β-thalassemia.

  6. Cardiac iron overload in chronically transfused patients with thalassemia, sickle cell anemia, or myelodysplastic syndrome

    Science.gov (United States)

    de Montalembert, Mariane; Ribeil, Jean-Antoine; Brousse, Valentine; Guerci-Bresler, Agnes; Stamatoullas, Aspasia; Vannier, Jean-Pierre; Dumesnil, Cécile; Lahary, Agnès; Touati, Mohamed; Bouabdallah, Krimo; Cavazzana, Marina; Chauzit, Emmanuelle; Baptiste, Amandine; Lefebvre, Thibaud; Puy, Hervé; Elie, Caroline

    2017-01-01

    The risk and clinical significance of cardiac iron overload due to chronic transfusion varies with the underlying disease. Cardiac iron overload shortens the life expectancy of patients with thalassemia, whereas its effect is unclear in those with myelodysplastic syndromes (MDS). In patients with sickle cell anemia (SCA), iron does not seem to deposit quickly in the heart. Our primary objective was to assess through a multicentric study the prevalence of cardiac iron overload, defined as a cardiovascular magnetic resonance T2*8 ECs in the past year, and age older than 6 years. We included from 9 centers 20 patients with thalassemia, 41 with SCA, and 25 with MDS in 2012-2014. Erythrocytapharesis did not consistently prevent iron overload in patients with SCA. Cardiac iron overload was found in 3 (15%) patients with thalassemia, none with SCA, and 4 (16%) with MDS. The liver iron content (LIC) ranged from 10.4 to 15.2 mg/g dry weight, with no significant differences across groups (P = 0.29). Abnormal T2* was not significantly associated with any of the measures of transfusion or chelation. Ferritin levels showed a strong association with LIC. Non-transferrin-bound iron was high in the thalassemia and MDS groups but low in the SCA group (P<0.001). Hepcidin was low in thalassemia, normal in SCA, and markedly elevated in MDS (P<0.001). Two mechanisms may explain that iron deposition largely spares the heart in SCA: the high level of erythropoiesis recycles the iron and the chronic inflammation retains iron within the macrophages. Thalassemia, in contrast, is characterized by inefficient erythropoiesis, unable to handle free iron. Iron accumulation varies widely in MDS syndromes due to the competing influences of abnormal erythropoiesis, excess iron supply, and inflammation. PMID:28257476

  7. β-Thalassemia Distribution in the Old World: an Ancient Disease Seen from a Historical Standpoint

    Science.gov (United States)

    De Sanctis, Vincenzo; Kattamis, Christos; Canatan, Duran; Soliman, Ashraf T.; Elsedfy, Heba; Karimi, Mehran; Daar, Shahina; Wali, Yasser; Yassin, Mohamed; Soliman, Nada; Sobti, Praveen; Al Jaouni, Soad; El Kholy, Mohamed; Fiscina, Bernadette; Angastiniotis, Michael

    2017-01-01

    Background Haemoglobinopathies constitute the commonest recessive monogenic disorders worldwide, and the treatment of affected individuals presents a substantial global disease burden. β-thalassaemia is characterised by the reduced synthesis (β+) or absence (βo) of the β-globin chains in the HbA molecule, resulting in accumulation of excess unbound α-globin chains that precipitate in erythroid precursors in the bone marrow and in the mature erythrocytes, leading to ineffective erythropoiesis and peripheral haemolysis. Approximately 1.5% of the global population are heterozygotes (carriers) of the β-thalassemias; there is a high incidence in populations from the Mediterranean basin, throughout the Middle East, the Indian subcontinent, Southeast Asia, and Melanesia to the Pacific Islands. Aim The principal aim of this paper is to review, from a historical standpoint, our knowledge about an ancient disease, the β-thalassemias, and in particular, when, how and in what way β-thalassemia spread worldwide to reach such high incidences in certain populations. Results Mutations involving the β-globin gene are the most common cause of genetic disorders in humans. To date, more than 350 β-thalassaemia mutations have been reported. Considering the current distribution of β- thalassemia, the wide diversity of mutations and the small number of specific mutations in individual populations, it seems unlikely that β-thalassemia originated in a single place and time. Conclusions Various processes are known to determine the frequency of genetic disease in human populations. However, it is almost impossible to decide to what extent each process is responsible for the presence of a particular genetic disease. The wide spectrum of β-thalassemia mutations could well be explained by looking at their geographical distribution, the history of malaria, wars, invasions, mass migrations, consanguinity, and settlements. An analysis of the distribution of the molecular spectrum of

  8. Birth of healthy children after preimplantation diagnosis of β-thalassemia

    Institute of Scientific and Technical Information of China (English)

    焦泽旭; 庄广伦; 周灿权; 舒益民; 李洁; 梁晓燕

    2004-01-01

    Background Clinical programs for preventing β-thalassemia are presently based on prospective carrier screening and prenatal diagnosis. This paper report an achievement of a pregnancy with unaffected embryos using in vitro fertilization and embryo transfer (IVF-ET), in combination with preimplantation genetic diagnosis (PGD), for a couple at risk of having children with β-thalassemia.Methods A couple carrying different thalassemia mutations, both a codon 41-42 mutation and the IVS Ⅱ 654 mutation, received standard IVF treatment, with intracytoplasmic sperm injection, embryo biopsiy, single cell polymerase chain reaction (PCR) and DNA analysis. Only unaffected or carrier embryos were transferred to the uterine cavity. After confirmation of pregnancy, a prenatal diagnosis was performed.Results Of a total of 13 embryos analyzed for β-globin mutations, PGD indicated that 2 were normal,3 were affected, and 6 were carriers. Diagnosis could not be made in the other 2 embryos. Three embryos were transferred to the uterus on the third day after oocyte retrieval. Ultrasonography revealed a twin pregnancy with one blighted ovum. The prenatal genetic diagnosis revealed that both fetuses were unaffected, and two healthy boys were born, confirming the results of PGD.Conclusions We developed a single-cell based primer extension preamplification (PEP)-PCR assay for the detection of β-thalassemia mutations. The assays were efficient and accurate at all stages of the procedure, and resulted in the birth of PGD-confirmed β-thalassemia free children in China. PEP was used here in PGD for β-thalassemia.

  9. Prevalence of β-thalassemia and other haemoglobinopathies in six cities in India: a multicentre study.

    Science.gov (United States)

    Mohanty, D; Colah, R B; Gorakshakar, A C; Patel, R Z; Master, D C; Mahanta, J; Sharma, S K; Chaudhari, U; Ghosh, M; Das, S; Britt, R P; Singh, S; Ross, C; Jagannathan, L; Kaul, R; Shukla, D K; Muthuswamy, V

    2013-01-01

    The population of India is extremely diverse comprising of more than 3,000 ethnic groups who still follow endogamy. Haemoglobinopathies are the commonest hereditary disorders in India and pose a major health problem. The data on the prevalence of β-thalassemias and other haemoglobinopathies in different caste/ethnic groups of India is scarce. Therefore the present multicentre study was undertaken in six cities of six states of India (Maharashtra, Gujarat, West Bengal, Assam, Karnataka and Punjab) to determine the prevalence of haemoglobinopathies in different caste/ethnic groups using uniform methodology. Fifty-six thousand seven hundred eighty individuals (college students and pregnant women) from different caste/ethnic groups were screened. RBC indices were measured on an automated haematology counter while the percentage of HbA(2), HbF and other abnormal Hb variants were estimated by HPLC on the Variant Hemoglobin Testing System. The overall prevalence of β-thalassemia trait was 2.78 % and varied from 1.48 to 3.64 % in different states, while the prevalence of β-thalassemia trait in 59 ethnic groups varied from 0 to 9.3 %. HbE trait was mainly seen in Dibrugarh in Assam (23.9 %) and Kolkata in West Bengal (3.92 %). In six ethnic groups from Assam, the prevalence of HbE trait varied from 41.1 to 66.7 %. Few subjects with δβ-thalassemia, HPFH, HbS trait, HbD trait, HbE homozygous and HbE β-thalassemia as well as HbS homozygous and HbS-β-thalassemia (India.

  10. β-Thalassemia Intermedia in Northern Iraq: A Single Center Experience

    Directory of Open Access Journals (Sweden)

    Nasir A. S. Al-Allawi

    2014-01-01

    Full Text Available To investigate the molecular basis of β-thalassemia intermedia in Northern Iraq and evaluate its management practices, a total of 74 patients from 51 families were enrolled. The patients were clinically and hematologically reevaluated, and had their β-thalassemia mutations characterized, as well as the number of α-globin genes and Xmn I Gγ −158 (C>T polymorphism studied. Out of 14 β-thalassemia mutations identified, the four most common were IVS-I-6 (T>C [33.3%], IVS-II-I (G>A [21.1%], codon 82/83(−G [10.1%], and codon 8 (−AA [8.1%]. The most common contributing factors to the less severe phenotype of thalassemia intermedia were found to be the inheritance of mild β-thalassemia alleles and the Xmn I polymorphism, while concomitant α-thalassemia had a limited role. Several complications were documented including: pulmonary hypertension in 20.4%, diabetes mellitus in 1.4%, hypothyroidism in 2.9%, and heart failure in 2.7%, while no documented cases of venous thrombosis were found. Compared to their counterparts in several Mediterranean countries, it appears that our patients were much less frequently transfused and had a lower proportion of patients who were splenectomized, on iron chelation, or hydroxycarbamide therapy. Such practices require further scrutiny to ensure that a better level of care is provided and that growth retardation, skeletal changes, and other complications are prevented or reduced.

  11. The organization of the gamma-delta-beta gene complex in normal and thalassemia cells.

    Science.gov (United States)

    Bank, A; Mears, J G; Ramirez, F; Burns, A L; Spence, S; Feldenzer, J; Baird, M

    1980-01-01

    Restriction enzyme digestion analysis and direct human globin gene cloning have permitted analysis of the physical arrangement of nucleotide sequences within and surrounding the human globin genes. With these methods it has been shown that the linear arrangement 5' to 3' of the globin genes is G gamma-A gamma-delta-beta. The G gamma and A gamma genes are separated by about 3.5 kilobases (kb), while the A gamma and delta genes are 15 kb apart, and the delta and beta 6.5 kb apart. Each of these genes contains a large intervening sequence (IVS) of approximately 1 kb in precisely the same position between condons 104 and 105. In addition, each of these genes has a small IVS between codons 30 and 31. In homozygous delta beta thalassemia DNA, there is deletion of all of the normal delta and beta gene fragments. However, a new fragment 4.2 kb in size containing the 5' end of the delta globin gene is retained. Retention of this fragment in delta beta thalassemia, but not in HPFH is consistent with a role for sequences in this region for limiting gamma globin gene expression. Studies to date suggest that the beta + and beta 0 thalassemias will be due to a heterogeneous group of DNA defects affecting either beta globin gene transcription or beta mRNA processing. In most cases of beta + and beta 0 thalassemia DNA analyzed, there is no detectable deletion of beta or delta genes. In three India beta 0 patients, deletion of the 3' end of the beta gene has been found. Analysis of cloned beta globin genes from a patient with beta + thalasseia shows differences from normal in the fragments generated by restriction enzymes which cut frequently. Whether these differences are responsible for the defect in thalassemia or are polymorphisms unrelated to thalassemia remains to be determined.

  12. SALIVA IRON AND FERRITIN LEVELS IN PATIENTS WITH THALASSEMIA AND IRON DEFICIENCY ANEMIA

    Directory of Open Access Journals (Sweden)

    Duran Canatan

    2012-01-01

    Full Text Available

    Most of the  techniques for measuring iron accumulation such as serum iron concentration, iron binding capacity, serum ferritin level, liver biopsy are invasive and hard methods for patients. The changes in trace element concentrations in saliva at different systemic diseases shows the quantity of the element at the body. The aim of this study was to compare the levels of iron and ferritin in saliva and serum in patients  with thalassemia and iron deficiency anemia. For this purpose, 35 healthy children as control group and 71 thalassemia major, 10 thalassemia intermedia and 15 thalassemia trait patients were involved. Their saliva  and serum iron and ferritin levels were measured.  There was no statistically difference between age and gender in all groups and control group (p>0.05.  In all groups saliva iron levels are higher than serum iron levels(p<0.05. Furthermore there was a positive correlation betwen serum and saliva  iron levels in thalassemia major, intermedia and trait groups ( p=0.000, r=0.972, r=0.720, r=0.955 and also there was a positive correlation between serum and saliva iron levels in control and iron deficiency group (p= 0.000, r= 0.885, r= 0.368.  In conclusion,  Saliva iron and ferritin levels increase  as well as serum in patients with thalassemia and decrease in patients with iron deficiency anemia. Saliva can be used for diagnosis routinely  to shows the iron overload  and deficiency of the body and its easy applicability and also a non-invasive procedure is important advantage.

  13. SALIVA IRON AND FERRITIN LEVELS IN PATIENTS WITH THALASSEMIA AND IRON DEFICIENCY ANEMIA

    Directory of Open Access Journals (Sweden)

    Duran Canatan

    2012-08-01

    Full Text Available Most of the  techniques for measuring iron accumulation such as serum iron concentration, iron binding capacity, serum ferritin level, liver biopsy are invasive and hard methods for patients. The changes in trace element concentrations in saliva at different systemic diseases shows the quantity of the element at the body. The aim of this study was to compare the levels of iron and ferritin in saliva and serum in patients  with thalassemia and iron deficiency anemia. For this purpose, 35 healthy children as control group and 71 thalassemia major, 10 thalassemia intermedia and 15 thalassemia trait patients were involved. Their saliva  and serum iron and ferritin levels were measured.  There was no statistically difference between age and gender in all groups and control group (p>0.05.  In all groups saliva iron levels are higher than serum iron levels(p<0.05. Furthermore there was a positive correlation betwen serum and saliva  iron levels in thalassemia major, intermedia and trait groups ( p=0.000, r=0.972, r=0.720, r=0.955 and also there was a positive correlation between serum and saliva iron levels in control and iron deficiency group (p= 0.000, r= 0.885, r= 0.368.  In conclusion,  Saliva iron and ferritin levels increase  as well as serum in patients with thalassemia and decrease in patients with iron deficiency anemia. Saliva can be used for diagnosis routinely  to shows the iron overload  and deficiency of the body and its easy applicability and also a non-invasive procedure is important advantage.

  14. Iron Chelation Adherence to Deferoxamine and Deferasirox in Thalassemia

    Science.gov (United States)

    Trachtenberg, Felicia; Vichinsky, Elliott; Haines, Dru; Pakbaz, Zahra; Mednick, Lauren; Sobota, Amy; Kwiatkowski, Janet; Thompson, Alexis A.; Porter, John; Coates, Thomas; Giardina, Patricia J.; Olivieri, Nancy; Yamashita, Robert; Neufeld, Ellis J.

    2015-01-01

    The Thalassemia Clinical Research Network collected adherence information from 79 patients on deferoxamine and 186 on deferasirox from 2007 to 2009. Chelation adherence was defined as percent of doses administered in the last 4 weeks (patient report) out of those prescribed (chart review). Chelation history since 2002 was available for 97 patients currently on deferoxamine and 217 on deferasirox, with crude estimates of adherence from chart review. Self-reported adherence to both deferoxamine and deferasirox were quite high, with slightly higher adherence to the oral chelator (97 vs. 92%). Ninety percent of patients on deferasirox reported at least 90% adherence, compared with 75% of patients on deferoxamine. Adherence to both chelators was highest in children, followed by adolescents and older adults. Predictors of lower deferoxamine adherence were smoking in the past year, problems sticking themselves (adults only), problems wearing their pump, and fewer transfusions in the past year. Predictors of lower deferasirox adherence were bodily pain and depression. Switching chelators resulted in increased adherence, regardless of the direction of the switch, although switching from deferoxamine to deferasirox was far more common. As adherence to deferoxamine is higher than previously reported, it appears beneficial for patients to have a choice in chelators. PMID:21523808

  15. Iron chelation adherence to deferoxamine and deferasirox in thalassemia.

    Science.gov (United States)

    Trachtenberg, Felicia; Vichinsky, Elliott; Haines, Dru; Pakbaz, Zahra; Mednick, Lauren; Sobota, Amy; Kwiatkowski, Janet; Thompson, Alexis A; Porter, John; Coates, Thomas; Giardina, Patricia J; Olivieri, Nancy; Yamashita, Robert; Neufeld, Ellis J

    2011-05-01

    The Thalassemia Clinical Research Network collected adherence information from 79 patients on deferoxamine and 186 on deferasirox from 2007 to 2009. Chelation adherence was defined as percent of doses administered in the last 4 weeks (patient report) out of those prescribed(chart review). Chelation history since 2002 was available for 97 patients currently on deferoxamine and 217 on deferasirox, with crude estimates of adherence from chart review. Self-reported adherence to both deferoxamine and deferasirox were quite high, with slightly higher adherence to the oral chelator (97 vs. 92%). Ninety percent of patients on deferasirox reported at least 90% adherence, compared with 75% of patients on deferoxamine. Adherence to both chelators was highest in children, followed by adolescents and older adults.Predictors of lower deferoxamine adherence were smoking in the past year, problems sticking themselves (adults only), problems wearing their pump, and fewer transfusions in the past year. Predictors of lower deferasirox adherence were bodily pain and depression. Switching chelators resulted in increased adherence, regardless of the direction of the switch, although switching from deferoxamine to deferasirox was far more common. As adherence to deferoxamine is higher than previously reported, it appears beneficial for patients to have a choice in chelators.

  16. Spinal cord compression in {beta}-thalassemia: follow-up after radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Fonseca, Silvana Fahel da; Figueiredo, Maria Stella; Cancado, Rodolfo Delfini; Nakadakare, Fernando; Segreto, Roberto; Kerbauy, Jose [Universidade Federal de Sao Paulo (UNIFESP), SP (Brazil). Escola Paulista de Medicina

    1998-12-01

    Spinal cord compression due to extramedullary hematopoiesis is a well-described bu rare syndrome encountered in several hematologic disorders, including {beta}-thalassemia. We report a case of a patient with intermediate {beta}-thalassemia and crural paraparesis due to spinal cord compression by a paravertebral extramedullary mass. She was successfully treated with low-dose radiotherapy and transfusions. After splenectomy, she was regularly followed up for over four years without transfusion or recurrence of spinal cord compression. Extramedullary hematopoiesis should be investigated in patients with hematologic disorders and spinal cord symptoms. The rapid recognition and treatment with radiotherapy can dramatically alleviate symptoms. (author)

  17. Spinal cord compression in b-thalassemia: follow-up after radiotherapy

    Directory of Open Access Journals (Sweden)

    Silvana Fahel da Fonseca

    Full Text Available CONTEXT: Spinal cord compression due to extramedullary hematopoiesis is a well-described but rare syndrome encountered in several clinical hematologic disorders, including b-thalassemia. CASE REPORT: We report the case of a patient with intermediate b-thalassemia and crural paraparesis due to spinal cord compression by a paravertebral extramedullary mass. She was successfully treated with low-dose radiotherapy and transfusions. After splenectomy, she was regularly followed up for over four years without transfusion or recurrence of spinal cord compression. DISCUSSION: Extramedullary hematopoiesis should be investigated in patients with hematologic disorders and spinal cord symptoms. The rapid recognition and treatment with radiotherapy can dramatically alleviate symptoms.

  18. From Blogs to Bottle Caps

    Science.gov (United States)

    Edinger, Ted

    2012-01-01

    There is a wonderful community of art educators connecting a once-isolated profession through blogging. Art educators around the world are sharing ideas and communicating with their peers through this amazing resource. In this article, the author describes the bottle cap mural at Tulip Grove Elementary School which was inspired by this exchange of…

  19. Afterglow-reabsorbed H/sub alpha/ line delay effect in an expanding laser plasma

    Energy Technology Data Exchange (ETDEWEB)

    Derzhiev, V.I.; Zhidkov, A.G.; Maiorov, S.A.; Yakovlenko, S.I.

    1987-11-28

    The absorption of H/sub ..cap alpha../ line radiation is shown to lead to delay and even to non-monotonic afterglowing if observed along the 'line' of the expanding laser plasma. This makes it possible to explain the emission character of the H/sub ..cap alpha../ line of the O VIII ion (lambda = 10.2 nm) in experiments with 'Novette' set-ups.

  20. Exploring the role of hepcidin, an antimicrobial and iron regulatory peptide, in increased iron absorption in beta-thalassemia.

    Science.gov (United States)

    Breda, Laura; Gardenghi, Sara; Guy, Ella; Rachmilewitz, Eliezer A; Weizer-Stern, Orly; Adamsky, Konstantin; Amariglio, Ninette; Rechavi, Gideon; Giardina, Patricia J; Grady, Robert W; Rivella, Stefano

    2005-01-01

    To develop new treatments for beta-thalassemia, it is essential to identify the genes involved in the relevant pathophysiological processes. Iron metabolism in thalassemia mice being investigated, focusing on the expression of a gene called hepcidin (Hamp), which is expressed in the liver and whose product (Hamp) is secreted into the bloodstream. In mice, iron overload leads to overexpression of Hamp, while Hamp-knockout mice suffer from hemochromatosis. The aim of this study is to investigate Hamp in the mouse model of beta-thalassemia and to address the potential gene transfer of Hamp to prevent abnormal iron absorption.

  1. An intracranial extramedullary hematopoiesis in a 34-year-old man with beta thalassemia: a case report

    Directory of Open Access Journals (Sweden)

    Tabesh Homayoun

    2011-12-01

    Full Text Available Abstract Introduction Extramedullary hematopoiesis occurs in approximately 15% of cases of thalassemia. Intracranial deposits of extramedullary hematopoiesis are an extremely rare compensatory process in intermediate and severe thalassemia. Case presentation We present an unusual case of an intracranial extramedullary hematopoiesis with a choroid plexus origin in a 34-year-old Caucasian man with beta thalassemia intermedia, who presented with the complaints of chronic headache and rapid progressive visual loss. Conclusion An intracranial extramedullary hematopoiesis, although extremely rare, should be considered as a potential ancillary diagnosis in any thalassemic patient and therefore appropriate studies should be performed to investigate the probable intracranial ectopic marrow before any surgical intervention.

  2. ATLAS End Cap toroid in upstanding position

    CERN Multimedia

    2005-01-01

    End Cap toroid The ATLAS End Cap toroid weights 240-ton and is 12-m diameter high. The parts of this vacuum vessel had to be integrated and tested so that End Cap Toroid has no leaks. After that it could be cooled down to 80 K.

  3. Analyses of hydraulic performance of velocity caps

    DEFF Research Database (Denmark)

    Christensen, Erik Damgaard; Degn Eskesen, Mark Chr.; Buhrkall, Jeppe;

    2014-01-01

    The hydraulic performance of a velocity cap has been investigated. Velocity caps are often used in connection with offshore intakes. CFD (computational fluid dynamics) examined the flow through the cap openings and further down into the intake pipes. This was combined with dimension analyses...

  4. Motion of polar cap arcs

    Science.gov (United States)

    Hosokawa, K.; Moen, J. I.; Shiokawa, K.; Otsuka, Y.

    2011-01-01

    A statistics of motion of polar cap arcs is conducted by using 5 years of optical data from an all-sky imager at Resolute Bay, Canada (74.73°N, 265.07°E). We identified 743 arcs by using an automated arc detection algorithm and statistically examined their moving velocities as estimated by the method of Hosokawa et al. (2006). The number of the arcs studied is about 5 times larger than that in the previous statistics of polar cap arcs by Valladares et al. (1994); thus, we could expect to obtain more statistically significant results. Polar cap arcs are found to fall into two distinct categories: the By-dependent and By-independent arcs. The motion of the former arcs follows the rule reported by Valladares et al. (1994), who showed that stable polar cap arcs move in the direction of the interplanetary magnetic field (IMF) By. About two thirds of the arcs during northward IMF conditions belong to this category. The latter arcs always move poleward irrespective of the sign of the IMF By, which possibly correspond to the poleward moving arcs in the morning side reported by Shiokawa et al. (1997). At least one third of the arcs belong to this category. The By-dependent arcs tend to move faster when the magnitude of the IMF By is larger, suggesting that the transport of open flux by lobe reconnection from one polar cap compartment to the other controls their motion. In contrast, the speed of the By-independent arcs does not correlate with the magnitude of the By. The motions of both the By-dependent and By-independent arcs are most probably caused by the magnetospheric convection. Convection in the region of By-dependent arcs is affected by the IMF By, which indicates that their sources may be on open field lines or in the closed magnetosphere adjacent to the open-closed boundary, whereas By-independent arcs seem to be well on closed field lines. Hence, the magnetospheric source of the two types of arc may be different. This implies that the mechanisms causing the

  5. Could Heterozygous Beta Thalassemia Provide Protection Against Multiple Sclerosis?

    Science.gov (United States)

    Cikrikcioglu, Mehmet Ali; Ozcan, Muhammed Emin; Halac, Gulistan; Gultepe, Ilhami; Celik, Kenan; Sekin, Yahya; Eser, Elif Ece; Burhan, Sebnem; Cetin, Guven; Uysal, Omer

    2016-01-01

    Background Heterozygous beta thalassemia (HBT) has been proposed to increase the risk of developing autoimmune disease. Our aim in this study was to examine the prevalence of HBT among multiple sclerosis (MS) patients. Material/Methods HBT frequency was investigated in our MS group (243 patients with MS). Hemoglobin electrophoresis (HE) was carried out if MS patients had a mean corpuscular volume of (MCV) <80 fL and a mean corpuscular hemoglobin level of (MCH) <27 pg/L according to a complete blood count (CBC). If MCV was lower than 80 fL, MCH was lower than 27 pg/L, and Hemoglobin A2 equal to or higher than 3.5%, a diagnosis of HBT was established. The frequency of patients with HBT in our MS patient group was statistically compared with the prevalence of HBT in the city of Istanbul, where our MS patients lived. Results The HBT prevalence was 0.823% (2 patients) in the MS patient group. The prevalence of HBT in Istanbul has been reported to be 4.5%. According to the z-test, the HBT prevalence in our MS patient group was significantly lower than that in Istanbul (Z=6.3611, two-sided p value <0.0001, 95% confidence interval of prevalence of HBT in our MS patient group: 0.000998–0.029413). Conclusions Contrary to our hypothesis at the outset of study, the reduced HBT prevalence in the MS group compared to HBT frequency in the city of Istanbul might indicate that HBT is protective against MS. PMID:27941710

  6. Evaluation of Bone Mineral Density in Children with Thalassemia Major

    Directory of Open Access Journals (Sweden)

    Betül Bakan

    2012-12-01

    Full Text Available Aim: Fragile bones develop due to various factors in thalassemic patients. Even with optimum management, osteoporosis occurs, contributing to morbidity in majority of patients with thalassemia major (TM. Our aim was to evaluate bone health of thalassemic children using biochemical parameters and bone mineral density (BMD, and to emphasize the precautionary measures and early diagnosis of osteoporosis. Material and Methods: Thirteen children (5 females, 8 males, age <18 years with TM were included in the study. Age, duration, weight, height, transfusion frequency, medication use were recorded. Following laboratory analysis were obtained: Whole blood count, fasting blood glucose, ferritin, alanine aminotransferase, aspartate aminotransferase, calcium, phosphorus, alkaline phosphatase, thyroid stimulating hormone, free thyroxin, and intact parathyroid hormone (iPTH. BMD was determined using dual energy X-ray absorptiometry (DXA from femur and lumbar vertebrae. Patients with DXA Z-score <-2 was defined as osteoporotic. Results: The mean age was 7.85±3.17 years and body mass index (BMI was 14.68±1.93 kg/m2. The rest of the results were as follows: Lumbar BMD 0.464±0.108 g/cm2; total femur BMD 0.581± 0.114 g/cm2; lumbar DEXA Z-score 2.44±1.60; total femur DEXA -0.93±1.19. Osteoporosis ratio was determined as 69% in the lumbar vertebrae and 10% in the femur. A significant positive correlation was found between lumbar-femoral BMD and BMI, and a significant negative correlation was observed between femoral BMD and iPTH. Conclusion: BMD is low in thalassemic children. Despite regular transfusions and chelation therapy, osteoporosis starts early in life. (Turkish Journal of Osteoporosis 2012;18: 72-7

  7. Comparative analysis of the ATRX promoter and 5' regulatory region reveals conserved regulatory elements which are linked to roles in neurodevelopment, alpha-globin regulation and testicular function

    OpenAIRE

    Tang, Paisu; Frankenberg, Stephen; Argentaro, Anthony; Graves, Jennifer M; Familari, Mary

    2011-01-01

    Background ATRX is a tightly-regulated multifunctional protein with crucial roles in mammalian development. Mutations in the ATRX gene cause ATR-X syndrome, an X-linked recessive developmental disorder resulting in severe mental retardation and mild alpha-thalassemia with facial, skeletal and genital abnormalities. Although ubiquitously expressed the clinical features of the syndrome indicate that ATRX is not likely to be a global regulator of gene expression but involved in regulating specif...

  8. Iron Overload Leading to Torsades de Pointes in β-Thalassemia and Long QT Syndrome

    DEFF Research Database (Denmark)

    Refaat, Marwan M; El Hage, Lea; Steffensen, Annette Buur

    2016-01-01

    The authors present a unique case of torsades de pointes in a β-thalassemia patient with early iron overload in the absence of any structural abnormalities as seen in hemochromatosis. Genetic testing showed a novel KCNQ1 gene mutation 1591C>T [Gln531Ter(X)]. Testing of the gene mutation in Xenopu...

  9. Ethical issues of unrelated hematopoietic stem cell transplantation in adult thalassemia patients

    Directory of Open Access Journals (Sweden)

    Piras Eugenia

    2011-03-01

    Full Text Available Abstract Background Beta thalassemia major is a severe inherited form of hemolytic anemia that results from ineffective erythropoiesis. Allogenic hematopoietic stem cell transplantation (HSCT remains the only potentially curative therapy. Unfortunately, the subgroup of adult thalassemia patients with hepatomegaly, portal fibrosis and a history of irregular iron chelation have an elevated risk for transplantation-related mortality that is currently estimated to be about 29 percent. Discussion Thalassemia patients may be faced with a difficult choice: they can either continue conventional transfusion and iron chelation therapy or accept the high mortality risk of HSCT in the hope of obtaining complete recovery. Throughout the decision making process, every effort should be made to sustain and enhance autonomous choice. The concept of conscious consent becomes particularly important. The patient must be made fully aware of the favourable and adverse outcomes of HSCT. Although it is the physician's duty to illustrate the possibility of completely restoring health, considerable emphasis should be put on the adverse effects of the procedure. The physician also needs to decide whether the patient is eligible for HSCT according to the "rule of descending order". The patient must be given full details on self-care and fundamental lifestyle changes and be fully aware that he/she will be partly responsible for the outcome. Summary Only if all the aforesaid conditions are satisfied can it be considered reasonable to propose unrelated HSCT as a potential cure for high risk thalassemia patients.

  10. β-Thalassemia Patients Revealed a Significant Change of Untargeted Metabolites in Comparison to Healthy Individuals

    Science.gov (United States)

    Musharraf, Syed Ghulam; Iqbal, Ayesha; Ansari, Saqib Hussain; Parveen, Sadia; Khan, Ishtiaq Ahmad; Siddiqui, Amna Jabbar

    2017-01-01

    β-Thalassemia is one of the most prevalent forms of congenital blood disorders characterized by reduced hemoglobin levels with severe complications, affecting all dimensions of life. The mechanisms underlying the phenotypic heterogeneity of β-thalassemia are still poorly understood. We aimed to work over metabolite biomarkers to improve mechanistic understanding of phenotypic heterogeneity and hence better management of disorder at different levels. Untargeted serum metabolites were analyzed after protein precipitation and SPE (solid phase extraction) from 100 β-thalassemia patients and 61 healthy controls using GC-MS. 40 metabolites were identified having a significance difference between these two groups at probability of 0.05 and fold change >1.5. Out of these 40 metabolites, 17 were up-regulated while 23 were down-regulated. PCA and PLS-DA model was also created that revealed a fine separation with a sensitivity of 70% and specificity of 100% on external validation of samples. Metabolic pathway analysis revealed alteration in multiple pathways including glycolysis, pyruvate, propanoate, glycerophospholipid, galactose, fatty acid, starch and sucrose metabolism along with fatty acid elongation in mitochondria, glycerolipid, glyoxylate and dicarboxylate metabolism pointing towards the shift of metabolism in β-thalassemia patients in comparison to healthy individuals. PMID:28198811

  11. A new β⁰-thalassemia frameshift mutation [β 48 (-T)] in a Uruguayan family.

    Science.gov (United States)

    Da Luz, J; López, P; Kimura, E M; Albuquerque, D M; Costa, F F; Sans, M; Sonati, M F

    2013-02-01

    We describe here a new frameshift mutation of β-thalassemia in a Uruguayan family with Italian ancestry [β48 (-T); HBB:c.146delT]. This frameshift results in formation of premature stop codon (TGA) 40 bp downstream and in a short unstable product that is degraded in the cell.

  12. Thalassemia in Western Australia: 11 novel deletions characterized by Multiplex Ligation-dependent Probe Amplification.

    NARCIS (Netherlands)

    Phylipsen, M.; Prior, J.F.; Lim, E.; Lingam, N.; Vogelaar, I.P.; Giordano, P.C.; Finlayson, J.; Harteveld, C.L.

    2010-01-01

    The number of immigrants in Western Australia from many different areas where hemoglobinopathies are endemic has increased dramatically since the 1970s. Therefore, many different thalassemia mutations have been introduced in the country, which add a technological diagnostic problem to the serious bu

  13. Oxidative modification and poor protective activity of HDL on LDL oxidation in thalassemia.

    Science.gov (United States)

    Unchern, Supeenun; Laohareungpanya, Narumon; Sanvarinda, Yupin; Pattanapanyasat, Kovit; Tanratana, Pansakorn; Chantharaksri, Udom; Sibmooh, Nathawut

    2010-07-01

    Oxidative modification of low-density lipoprotein (LDL) has been reported in thalassemia, which is a consequence of oxidative stress. However, the levels of oxidized high-density lipoprotein (HDL) in thalassemia have not been evaluated and it is unclear whether HDL oxidation may be linked to LDL oxidation. In this study, the levels of total cholesterol, iron, protein, conjugated diene (CD), lipid hydroperoxide (LOOH), and thiobarbituric acid reactive substances (TBARs) were determined in HDL from healthy volunteers and patients with beta-thalassemia intermedia with hemoglobin E (beta-thal/Hb E). The protective activity of thalassemic HDL on LDL oxidation was also investigated. The iron content of HDL(2) and HDL(3) from beta-thal/HbE patients was higher while the cholesterol content was lower than those in healthy volunteers. Thalassemic HDL(2) and HDL(3) had increased levels of lipid peroxidation markers i.e., conjugated diene, LOOH, and TBARs. Thalassemic HDL had lower peroxidase activity than control HDL and was unable to protect LDL from oxidation induced by CuSO(4). Our findings highlight the oxidative modification and poor protective activity of thalassemic HDL on LDL oxidation which may contribute to cardiovascular complications in thalassemia.

  14. Evidence for a novel mechanism independent of myocardial iron in β-thalassemia cardiac pathogenesis.

    Directory of Open Access Journals (Sweden)

    Ekatherina Stoyanova

    Full Text Available Human β-thalassemia major is one of the most prevalent genetic diseases characterized by decrease/absence of β-globin chain production with reduction of erythrocyte number. The main cause of death of treated β-thalassemia major patients with chronic blood transfusion is early cardiac complications that have been attributed to secondary iron overload despite optimal chelation. Herein, we investigated pathophysiological mechanisms of cardiovascular dysfunction in a severe murine model of β-thalassemia from 6 to 15-months of age in the absence of confounding effects related to transfusion. Our longitudinal echocardiography analysis showed that β-thalassemic mice first display a significant increase of cardiac output in response to limited oxygen-carrying erythrocytes that progressed rapidly to left ventricular hypertrophy and structural remodeling. Following this compensated hypertrophy, β-thalassemic mice developed age-dependent deterioration of left ventricular contractility and dysfunction that led toward decompensated heart failure. Consistently, murine β-thalassemic hearts histopathology revealed cardiac remodeling with increased interstitial fibrosis but virtual absence of myocardial iron deposits. Importantly, development of thalassemic cardiac hypertrophy and dysfunction independently of iron overload has uncoupled these cardiopathogenic processes. Altogether our study on β-thalassemia major hemoglobinopathy points to two successive phases resulting from severe chronic anemia and from secondarily induced mechanisms as pathophysiologic contributors to thalassemic cardiopathy.

  15. WHAT UNRELATED HEMATOPOIETIC STEM CELL TRANSPLANTATION IN THALASSEMIA TAUGHT US ABOUT TRANSPLANT IMMUNOGENETICS.

    Directory of Open Access Journals (Sweden)

    Giorgio La Nasa

    2016-10-01

    Full Text Available Abstract Although the past few decades have shown an improvement in the survival and complication-free survival rates in patients with beta-thalassemia major and gene therapy is already at an advanced stage of experimentation, hematopoietic stem cell transplantation (HSCT continues to be the only effective and realistic approach to the cure of this chronic non-malignant disease. Historically, human leukocyte antigen (HLA-matched siblings have been the preferred source of donor cells owing to superior outcomes compared with HSCT from other sources. Nowadays, the availability of an international network of voluntary stem cell donor registries and cordon blood banks has significantly increased the odds of finding a suitable HLA matched donor. Stringent immunogenetic criteria for donor selection have made it possible to achieve overall survival (OS and thalassemia-free survival (TFS rates comparable to those of sibling transplants. However, acute and chronic graft-versus-host disease (GVHD remains the most important complication in unrelated HSCT in thalassemia, leading to considerable rates of morbidity and mortality for a chronic non-malignant disease. A careful immunogenetic assessment of donors and recipients makes it possible to individuate appropriate strategies for its prevention and management. This review provides an overview on recent insights about immunogenetic factors involved in GVHD, which seem to have a potential role in the outcome of transplantation for thalassemia.

  16. Prevalência de talassemias e hemoglobinas variantes em pacientes com anemia não ferropênica Prevalence of thalassemias and variant hemoglobins in patients with non-ferropenic anemia

    Directory of Open Access Journals (Sweden)

    Sandrine C. Wagner

    2005-03-01

    patients with non-ferropenic anemia carried some type of inherited anemia: 25.9% of heterozygous alpha-thalassemia, 32.8% of heterozygous beta-thalassemia, 3.4% of heterozygosity for hemoglobin S (Hb AS and 1.7% of homozygosity for hemoglobin C (Hb CC. Inherited anemias were detected in 14.1% of the control group: 11.5% of alpha-thalassemia, 0.9% of beta-thalassemia, 1.3% of heterozygosity for hemoglobin S (Hb AS and 0.4% of heterozygosity for hemoglobin C (Hb AC. The results obtained showed that the prevalence of variant thalassemias and hemoglobins in the control group is coincident with that described in the literature. However, physicians and health services should be informed about the overwhelming prevalence of these inherited homeopathies in individuals with non-ferropenic anemia, due to its importance in the definitive diagnosis of anemia and for the correct therapeutic proceedings.

  17. IL28B polymorphisms influence stage of fibrosis and spontaneous or interferon-induced viral clearance in thalassemia patients with hepatitis C virus infection

    Science.gov (United States)

    Di Marco, Vito; Bronte, Fabrizio; Calvaruso, Vincenza; Capra, Marcello; Borsellino, Zelia; Maggio, Aurelio; Renda, Maria Concetta; Pitrolo, Lorella; Lo Pinto, Maria Carmela; Rizzo, Michele; Fiorenza, Flavia; Gerardi, Calogera; Grimaudo, Stefania; Di Cristina, Antonietta; Levrero, Massimo; Craxì, Antonio

    2012-01-01

    Background Polymorphisms in the interleukin-28B are important determinants in the spontaneous and drug-induced control of hepatitis C virus infection. Design and Methods We assessed the association of rs8099917 and rs12979860 polymorphisms with spontaneous viral clearance, severity of liver fibrosis, and response to interferon-monotherapy in 245 thalassemia major patients with hepatitis C virus infection. Results Ninety-eight patients (40%) had a spontaneous viral clearance while 147 patients (60%) developed a chronic infection. Spontaneous viral clearance was more frequent among patients with the T/T genotype of rs8099917 polymorphism (OR 2.130; P=0.008) or C/C genotype of rs12979860 polymorphism (OR 2.425; P=0.001). During observation, 131 patients with chronic infection underwent a liver biopsy; age (OR 1.058; P=0.01) G/T or G/G genotypes of rs8099917 polymorphism (OR 3.962; P=0.001), and C/T or T/T genotypes of rs12979860 polymorphism (OR 3.494; P=0.005) were associated with severe liver fibrosis, independent of liver iron concentration. Finally, T/T genotype of rs8099917 polymorphism (OR 3.014; P=0.03) or C/C genotype of rs12979860 polymorphism (OR 3.285; P=0.01), age (OR 0.902; P=0.001), female gender (OR 3.418; P=0.01) and 2 or 3 virus C genotypes (OR 4.700; P=0.007) were independently associated with sustained virological response in 114 patients treated with alpha-interferon. Conclusions Polymorphisms in the interleukin-28B are associated with the control of hepatitis C virus infection in thalassemia major patients, and understanding allelic patterns has an important role in determining prognosis and therapeutic management. PMID:22180419

  18. NMR structural characterization of the N-terminal domain of the adenylyl cyclase-associated protein (CAP) from Dictyostelium discoideum

    Energy Technology Data Exchange (ETDEWEB)

    Mavoungou, Chrystelle [Max Planck Institute for Biochemistry (Germany); Israel, Lars [Ludwig Maximilians-University, Adolf Butenandt Institute, Cell Biology (Germany); Rehm, Till; Ksiazek, Dorota; Krajewski, Marcin; Popowicz, Grzegorz [Max Planck Institute for Biochemistry (Germany); Noegel, Angelika A. [University of Cologne, Institute for Biochemistry (Germany); Schleicher, Michael [Ludwig Maximilians-University, Adolf Butenandt Institute, Cell Biology (Germany); Holak, Tad A. [Max Planck Institute for Biochemistry (Germany)

    2004-05-15

    Cyclase-associated proteins (CAPs) are highly conserved, ubiquitous actin binding proteins that are involved in microfilament reorganization. The N-termini of CAPs play a role in Ras signaling and bind adenylyl cyclase; the C-termini bind to G-actin. We report here the NMR characterization of the amino-terminal domain of CAP from Dictyostelium discoideum (CAP(1-226)). NMR data, including the steady state {sup 1}H-{sup 15}N heteronuclear NOE experiments, indicate that the first 50 N-terminal residues are unstructured and that this highly flexible serine-rich fragment is followed by a stable, folded core starting at Ser 51. The NMR structure of the folded core is an {alpha}-helix bundle composed of six antiparallel helices, in a stark contrast to the recently determined CAP C-terminal domain structure, which is solely built by {beta}-strands.

  19. NMR structural characterization of the N-terminal domain of the adenylyl cyclase-associated protein (CAP) from Dictyostelium discoideum.

    Science.gov (United States)

    Mavoungou, Chrystelle; Israel, Lars; Rehm, Till; Ksiazek, Dorota; Krajewski, Marcin; Popowicz, Grzegorz; Noegel, Angelika A; Schleicher, Michael; Holak, Tad A

    2004-05-01

    Cyclase-associated proteins (CAPs) are highly conserved, ubiquitous actin binding proteins that are involved in microfilament reorganization. The N-termini of CAPs play a role in Ras signaling and bind adenylyl cyclase; the C-termini bind to G-actin. We report here the NMR characterization of the amino-terminal domain of CAP from Dictyostelium discoideum (CAP(1-226)). NMR data, including the steady state (1)H-(15)N heteronuclear NOE experiments, indicate that the first 50 N-terminal residues are unstructured and that this highly flexible serine-rich fragment is followed by a stable, folded core starting at Ser 51. The NMR structure of the folded core is an alpha-helix bundle composed of six antiparallel helices, in a stark contrast to the recently determined CAP C-terminal domain structure, which is solely built by beta-strands.

  20. Estimation of the alpha decay half-lives

    Energy Technology Data Exchange (ETDEWEB)

    Poenaru, D.N.; Ivascu, M. (Institute for Physics and Nuclear Engineering, Bucharest (Romania))

    1983-07-01

    Improved up to date versions of the known ..cap alpha.. decay half-lives formulae are obtained by changing the additive parameters in order to have a vanishing mean value of the absolute errors. A new semiempirical relationship is derived on the grounds of the fission theory of alpha decay. It takes into consideration explicitly the dependence on the difference from magicity both of the neutron and proton numbers. Allowing us to obtain better agreement with experimental data.

  1. Benzonorbornadiene end caps for PMR resins

    Science.gov (United States)

    Panigot, Michael J.; Waters, John F.; Varde, Uday; Sutter, James K.; Sukenik, Chaim N.

    1992-01-01

    Several ortho-disubstituted benzonorbornadiene derivatives are described. These molecules contain acid, ester, or anhydride functionality permitting their use as end caps in PMR (polymerization of monomer reactants) polyimide systems. The replacement of the currently used norbornenyl end caps with benzonorbornadienyl end caps affords resins of increased aromatic content. It also allows evaluation of some mechanistic aspects of PMR cross-linking. Initial testing of N-phenylimide model compounds and of actual resin formulations using the benzonorbornadienyl end cap reveals that they undergo efficient thermal crosslinking to give oligomers with physical properties and thermal stability comparable to commercial norbornene-end-capped PMR systems.

  2. Investigating Challenges Facing Self-Management Empowerment Education in Adolescents and Youths with Major Thalassemia

    Directory of Open Access Journals (Sweden)

    Razzazan

    2014-10-01

    Full Text Available Background Thalassemia is considered an important public health problem worldwide, especially in developing and poor countries. Although several advanced techniques have been developed for prevention of thalassemia in the recent years, many adolescents and youths are still living with this disease. Independence from parents, decisions about high-risk behaviors, uncovering the identity, and adapting to mental and physical effects of the disease occur together in adolescents. Objectives This study was conducted to explore challenges of self-management empowerment in adolescents and youths with major thalassemia. Materials and Methods This was a descriptive-exploratory study. The study population consisted of adolescents and youths with major thalassemia who had medical records in the Bushehr Thalassemia Center, affiliated with Bushehr University of Medical Sciences. The study samples were purposively selected. Demographic information questionnaire and empowerment questionnaire were used to collect data from the semistructured interview. We analyzed qualitative data by content analysis method and quantitative data by descriptive (mean, standard deviation and analytical (Student's t-test, ANOVA and Pearson’s correlation coefficient statistical methods, using the statistical software SPSS 18. Results In qualitative part of the study, data from semistructured in-depth interviews with 15 participants were coded and summarized in five themes including: 1 awareness of personal changes; 2 need for adaptation; 3 maintaining independence and self-management; 4 uncovering the identity and role playing; and 5 sense of control and satisfaction. Results of the quantitative part showed that the overall score of participants on empowerment was 92.46 of 149 scores, which showed a moderate situation in the empowerment of these individuals. In addition, the empowerment score showed no statistically significant correlation with demographic characteristics

  3. EARLY PREDICTORS OF RENAL DYSFUNCTION IN Β-THALASSEMIA MAJOR AND INTERMEDIA PATIENTS

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    Azza A.G. Tantawy

    2004-09-01

    Full Text Available Background: Better survival of thalassemia patients allowed previously unrecognized renal complications to emerge. Objectives: Assess prevalence and early predictors of renal dysfunction in young β-thalassemia major (β-TM and intermedia (β-TI patients. Subjects: 66 β-TM (group I, 26 β-TI (group II Egyptian patients and 40 healthy controls. Methods: History, examination and investigations that included kidney function tests, serum ferritin, serum bicarbonate, plasma osmolality and urinary total proteins, microalbuminuria (MAU, N-acetyl-β-D-glucosaminidase (NAG, retinol binding protein (RBP, α-1 microglobulin, bicarbonate, osmolality, Creatinine clearance (CrCl, % fractional excretion of bicarbonate (% FE-HCO3. Results: The most common renal abnormality was proteinuria (71%, followed by increased urinary level of RBP (69.4%, NAG (58.1%, α-1 microglobulin (54.8% and microalbumin (29% and also decreased urinary osmolality (58.1%. Although serum creatinine and BUN were not statistically different between thalassemia patients and control, CrCl were significantly lowered in thalassemia patients. Total serum protein and albumin was significant lower in splenectomized β-TM, whereas urinary total protein and MAU were significantly increased in all thalassemia patients. NAG, RBP and α-1 microglobulin were negatively correlated with CrCl and positively correlated with serum ferritin and urinary total protein. Z-score analysis for discrimination of patients with renal dysfunction proved superiority of urine total protein and RBP. Comparative statistics of different frequencies revealed significant difference between the urinary total protein and both MAU and % FE-HCO3. Conclusion: Asymptomatic renal dysfunctions are prevalent in young β-TM and β-TI patients that necessitate regular screening and urinary total protein and RBP may be cost-effective for early detection.

  4. Prevalence and hematological characteristics of beta-thalassemia trait in Gaziantep urban area, Turkey.

    Science.gov (United States)

    Gurbak, Mehmet; Sivasli, Ercan; Coskun, Yavuz; Bozkurt, Ali Ihsan; Ergin, Ahmet

    2006-01-01

    Thalassemia is one of the most common hereditary disorders in the Mediterranean region and studies have shown that the prevalence of beta-thalassemia trait is high in the southern part of Turkey. Gaziantep is a city located near this region and, therefore, the authors investigated the prevalence and hematological characteristics of the beta-thalassemia traits in primary school students in Gaziantep. Sixty primary schools were selected from a list of all primary schools using a systematic sampling method. Data were collected by a face-to-face questionnaire. Osmotic fragility testing (OFT) using single-tube 0.36% NaCl solution was used for the screening of beta-thalassemia. Students who were positive in regard to OFT went through a series of testing, including a complete blood count, serum ferritin levels, serum iron, and hemoglobin electroforesis. Chi-square test was used in statistical analysis. Of the 2439 students enrolled to the study from the selected 60 classrooms, 1353 (55.5%) were male and 1086 (44.5%) were female. The OFT was positive in 115 (4.7%) of the participants. CEA and confirmatory HPLC results of the students who were positive OFT indicated that 70 (60.8%) had normal results, 33(28.7%) showed high HbA2 levels, 7 (6.1%) showed high HbA2 and HbF levels, 5(5.2%) showed high HbA2 and Fe-deficiency anemia, and none showed increased HbF levels. The overall prevalence of beta-thalassemia trait was 1.84%. No gender differentials and highest rates among the Kahramanmaras (3.5%) and Sanliurfa (1.7%) born students were the other significant findings of this study. Implementation of a routine carrier-screening program offering genetic counseling, prenatal diagnosis, and selective termination of affected fetuses would be a wise approach to eliminate this disease from the region.

  5. Prevalence of occult hepatitis C virus infection in Iranian patients with beta thalassemia major.

    Science.gov (United States)

    Bastani, Mohammad-Navid; Bokharaei-Salim, Farah; Keyvani, Hossein; Esghaei, Maryam; Monavari, Seyed Hamidreza; Ebrahimi, Mojtaba; Garshasebi, Saba; Fakhim, Shahin

    2016-07-01

    Occult hepatitis C virus infection (OCI) is a new pathological form of chronic hepatitis virus (HCV) infection characterized by the presence of HCV RNA in liver biopsy and/or peripheral blood mononuclear cell (PBMC) specimens and the absence of HCV RNA and anti-HCV antibodies (Abs) in plasma samples. β-thalassemia major is a hereditary recessive blood disease with deficiency in the hemoglobin beta chain. Thalassemic patients need blood transfusion therapy; repeated blood transfusion increases the risk of viral blood-borne infection. The aim of this study was to determine the prevalence of OCI in Iranian patients with β-thalassemia major. From February 2015 to November 2015, a total of 147 Iranian patients with β-thalassemia major were enrolled in this cross-sectional study. After extraction of viral RNA from the plasma and PBMC samples, HCV genomic RNA in the specimens was amplified by RT-nested PCR using primers from the 5'-UTR. The HCV genotypes of the positive specimens were tested using the RFLP assay. To confirm the HCV genotypes, the 5'-UTR fragment was amplified and cloned into the pJET1.2/blunt cloning vector and then sequenced. Out of 147 patients, 106 (72.1 %) were negative for anti-HCV Abs and HCV RNA. HCV RNA was found in PBMC specimens of six (5.7 %) patients, from a total of 106 patients with undetectable plasma HCV RNA and anti-HCV Abs. Therefore, six out of 106 patients had OCI. HCV genotyping revealed that three patients were infected with HCV subtype 1b, two patients were infected with HCV subtype 3a, and one patient was infected with HCV subtype 1a. These results revealed that Iranian patients with beta-thalassemia major might have OCI. Therefore, it seems that the design of a study to identify this infection in patients with β-thalassemia major would provide valuable information.

  6. The effect of eye movement and desensitization by reprocessing on depression in adolescents with Thalassemia

    Directory of Open Access Journals (Sweden)

    Shahnavazi

    2016-09-01

    Full Text Available Introduction: Thalassemia is the most common genetic diseases in the world and especially in our country. For many reasons, including chronic disease, health care costs, fear of early death, disease statues led to Depression, psychological and social problems in thalassemia patients. This study aimed to determine the efficacy of eye movement desensitization and processing efficiency of this method and to decreasing the Depression of children with thalassemia. Method: This study was a clinical trial. 60 thalassemic patients aged 20-12 years were randomly assigned to two groups. Demographic questionnaire and Beck Depression Inventory were used to collection of data. The trial of eye movement desensitization and reprocessing in 3 sessions on alternate days for 45 to 30 minutes after. Depression before and after the intervention were measured velocity. An analysis by descriptive statistics, t-test and paired t-test, Mann-Whitney and Wilcoxon tests Non parameter equal to the Kolmogorov-Smirnov test was performed. Results: This study shows that the mean or average level of Depression children with thalassemia before implementing EMDR therapy group27/73±3/52 was After doing EMDR therapy to 17/80±2/36 was Which is greatly reduced compared to pre-intervention and the results were statistically significant(P0<001. The result showed that EMDR has main full effect on decreasing the symptoms of Depression. Conclusion: The result showed that EMDR can useful through having the influence on integration information processing an effective method to treat or reduce Depression children with thalassemia.

  7. A Comparison of Quality of Life between Adolescences with Beta Thalassemia Major and their Healthy Peers

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    Shahram Baraz

    2016-01-01

    Full Text Available Background The chronic genetic blood disorder, thalassemia, affects Quality of life (QOL negatively. Regarding this, if adolescences with thalassemia are treated well, they will grow into an adult who will have a good potential for participating in society. Objectives: to determine the strongest predictor of QOL, compare QOL between the adolescents with beta-type major and their peers in Abadan city. Materials and Methods This was a cross-sectional study; the population consisted of 65 beta thalassemia major patients and 65  healthy peers with the same ages as the witness group. The data collection tools included SF-36 questionnaire and a questionnaire for demographic information. Data analysis was performed using independent t-test, correlation and linear regression by SPSS-16. Results The results of the study revealed that there is a significant difference (P < 0.05 in the average quality of life between the two groups of the study. On the other hand, the results showed that there was a meaningful relation between different aspects of life quality and family history of thalassemia            (P< 0.05. Also, there was a negative correlation between quality of life and the frequency of blood transfusion per year (P< 0.05. Conclusion Adolescences with beta thalassemia major do not have a desirable quality of life, therefore, this fact shows the necessity of serious reforming in various fields of health care, treatment, family, social and financial support, and rehabilitation that need more attention from health care policymakers.

  8. Evaluation of liver fibrosis in patients with thalassemia: the important role of hyaluronic acid.

    Science.gov (United States)

    Papastamataki, Maria; Delaporta, Polyxeni; Premetis, Evangelos; Kattamis, Antonios; Ladis, Vassilios; Papassotiriou, Ioannis

    2010-10-15

    Patients with transfusion-dependent thalassemia major often develop liver fibrosis due to liver iron overload and/or hepatitis virus C (HCV) infection. Hyaluronic acid (HA) plays a prominent role in the pathogenesis of liver fibrosis and the elevation of serum HA concentration is due to either increased synthesis by inflammatory cells and hepatic stellate cells or impaired degradation by sinusoidal endothelial cells (SECs) and thus is proposed as a non-invasive biomarker of liver fibrosis either by itself and/or included in the Hepascore formula. In this study we evaluated prospectively a screening of liver fibrosis in 201 adult patients aged 19-54 years with transfusion-dependent thalassemia major, based on HA measurements. 41/201 patients were HCV-RNA (+). HA was measured with a turbidimetric assay applied on a clinical chemistry analyzer. The Hepascore was computed from the results by using the model previously published. The main results of the study showed that: a) HA levels were increased in 110/201 (55%) thalassemia patients 85.0 ± 10.3 ng/ml, ranged from 15.0 to 1495.0 μg/l, compared to 20.8 ± 7.4 μg/l reference laboratory values, p0.324 and p>0.270, respectively). Our findings indicate that hyaluronic acid measurements contribute to the assessment of liver fibrosis in patients with thalassemia and might be helpful for further evaluation of patients with liver biopsy if this is truly needed. Furthermore, liver fibrosis in thalassemia seems to be independent from liver siderosis.

  9. In vitro refolding of heterodimeric CapZ expressed in E. coli as inclusion body protein.

    Science.gov (United States)

    Remmert, K; Vullhorst, D; Hinssen, H

    2000-02-01

    CapZ is a heterodimeric Ca(2+)-independent actin binding protein which plays an important role in organizing the actin filament lattice of cross-striated muscle cells. It caps the barbed end of actin filaments and promotes nucleation of actin polymerization, thereby regulating actin filament length. Here we report the expression of the two muscle-specific isoforms alpha2 and beta1, from chicken in Escherichia coli as individual subunits using the pQE60 expression vector and the subsequent renaturation of the functional CapZ heterodimer from inclusion bodies. Optimal renaturation conditions were obtained both by simultaneous refolding of urea-solubilized subunits and by rapid dilution into a buffer containing 20% glycerol, 5 mM EGTA, 2 mM DTT, 1 mM PMSF, and 100 mM Tris, pH 7.4. The refolding mixture was incubated for 24 h at 15 degrees C and the protein was concentrated by ultrafiltration. Biochemical characterization of the recombinant heterodimer revealed actin binding activities indistinguishable from those of native CapZ as purified from chicken skeletal muscle. Using the same protocol, we were able to refold the beta1, but not the alpha2 isoform as a single polypeptide, indicating a role for beta1 as a molecular template for the folding of alpha2. The reported recombinant approach leads to high yields of active heterodimer and allows the renaturation and characterization of the beta subunit.

  10. Gamma ray pulsars emission from extended polar cap cascades

    CERN Document Server

    Daugherty, J K; Daugherty, Joseph K; Harding, Alice K

    1995-01-01

    We have used a Monte Carlo simulation of a Polar Cap (PC) model of gamma-ray pulsars to estimate light curves and phase-resolved spectra for sources whose rotational and magnetic axes are oriented so that only one of the magnetic poles produces emission directed at the Earth. In this Single Polar Cap (SPC) scenario, even sources whose light curves have two distinct peaks (Crab, Vela, Geminga, PSR B1951+32) are due to emission concentrated near the rim of a single PC. If the inclination alpha is comparable to the half-width of the PC gamma-beam, alpha ~ theta_{b}, the peak-to-peak phase separation can have the large values (0.4 - 0.5) observed from these sources. In the model presented here we attribute the observed interpeak emission to pair cascades above the PC interior. Our simulation assumes the physics of conventional PC models, in which the gamma rays are due to photon-pair cascades initiated by curvature radiation from the acceleration of electrons above the PCs. In this work we assume that the acceler...

  11. Molecular analysis of beta-globin gene mutations among Thai beta-thalassemia children: results from a single center study

    Directory of Open Access Journals (Sweden)

    Boonyawat B

    2014-12-01

    Full Text Available Boonchai Boonyawat,1 Chalinee Monsereenusorn,2 Chanchai Traivaree2 1Division of Genetics, Department of Pediatrics, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand; 2Division of Hematology/Oncology, Department of Pediatrics, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand Background: Beta-thalassemia is one of the most common genetic disorders in Thailand. Clinical phenotype ranges from silent carrier to clinically manifested conditions including severe beta-thalassemia major and mild beta-thalassemia intermedia. Objective: This study aimed to characterize the spectrum of beta-globin gene mutations in pediatric patients who were followed-up in Phramongkutklao Hospital. Patients and methods: Eighty unrelated beta-thalassemia patients were enrolled in this study including 57 with beta-thalassemia/hemoglobin E, eight with homozygous beta-thalassemia, and 15 with heterozygous beta-thalassemia. Mutation analysis was performed by multiplex amplification refractory mutation system (M-ARMS, direct DNA sequencing of beta-globin gene, and gap polymerase chain reaction for 3.4 kb deletion detection, respectively. Results: A total of 13 different beta-thalassemia mutations were identified among 88 alleles. The most common mutation was codon 41/42 (-TCTT (37.5%, followed by codon 17 (A>T (26.1%, IVS-I-5 (G>C (8%, IVS-II-654 (C>T (6.8%, IVS-I-1 (G>T (4.5%, and codon 71/72 (+A (2.3%, and all these six common mutations (85.2% were detected by M-ARMS. Six uncommon mutations (10.2% were identified by DNA sequencing including 4.5% for codon 35 (C>A and 1.1% initiation codon mutation (ATG>AGG, codon 15 (G>A, codon 19 (A>G, codon 27/28 (+C, and codon 123/124/125 (-ACCCCACC, respectively. The 3.4 kb deletion was detected at 4.5%. The most common genotype of beta-thalassemia major patients was codon 41/42 (-TCTT/codon 26 (G>A or betaE accounting for 40%. Conclusion: All of the beta-thalassemia alleles have been characterized by

  12. Molecular Mechanism of Yisui Shengxue Granule, a Complex Chinese Medicine, on Thalassemia Patients Suffering from Hemolysis and Anemia of Erythrocytes

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    Na-Li Chu

    2014-01-01

    Full Text Available The objective of this study was to investigate the therapeutic biological mechanism of Yisui Shengxue Granule (YSSXG, a complex Chinese medicine, on the hemolysis and anemia of erythrocytes from patient with thalassemia disease. Sixteen patients with thalassemia (8 cases of α-thalassemia and 8 cases of β-thalassemia disease were collected and treated with YSSXG for 3 months. The improvements of blood parameter demonstrated that YSSXG had a positive clinical effect on patients with thalassemia disease. For patients with α-thalassemia disease, RT-PCR showed that YSSXG upregulated the relative mRNA expression level of α-globin to β-globin and downregulated DNMT1, DNMT3a, and DNMT3b mRNA compared with pretreatment. Western blotting showed that YSSXG downregulated the expression of DNMT1 and DNMT3a. For patients with β-thalassemia disease, the relative expression level of Aγ-globin to α-globin had an increasing trend and the level of BCL11A mRNA expression obviously increased. For all patients, RT-PCR showed that YSSXG upregulated mRNA expression of SPTA1 and SPTB. Activities of SOD and GSH-Px significantly increased and MDA obviously reduced on erythrocyte and blood serum after YSSXG treatment. TEM showed that YSSXG decreased the content of inclusion bodies. Activities of Na+K+-ATPtase and T-ATPtase of erythrocyte increased significantly after YSSXG treatment. This study provides the basis for mechanisms of YSSXG on thalassemia suffering with hemolysis and anemia of erythrocytes from patient.

  13. Diagnosis and Genotyping of Thalassemia%地中海贫血诊断与基因分型

    Institute of Scientific and Technical Information of China (English)

    刘春利

    2011-01-01

    地中海贫血(THAC)主要分部在我国海南及两广沿海地区.采用红细胞脆性试验、平均红细胞容积(MCV)、平均红细胞血红蛋白(MCH)测定、HbA2电泳测定和基因芯片技术,对THAC做出诊断.重症α地中海贫血可导致死产、死胎,影响孕妇健康;重症β地中海贫血表现为严重溶血性贫血,肝脾肿大,患者未到成年已夭折.地中海贫血杂合子临床症状轻且可无症状,夫妇双方携带,将有1/4生育重症地中海贫血儿的可能,故在地中海贫血高发区开展筛查与诊断非常重要.%In China, thalassemia (TH AC ) occurs most frequently in Hainan, and coastal areas of Guandong and Guangxi. Thalassemia can be diagnosed by erythrocyte fragility test, detection of MCV and MCH, HbA2 electrophoresis determination and gene chip technology. The severe α thalassemia can cause the stillbirth and fetal death, and be harmful to health pregnant women. The severe β thalassemia is presented as a severe hemolytic anemia and hepatosplenomegaly, and patients often died before adulthood. The thalassemia heterozygote has slight clinical symptoms or no symptom at all. When couple both carries this type of thalassemia, the possibility of their infant with severe thalassemia is 25%, so it is very important to implement the screening and diagnosis of thalassemia in high incidence the areas.

  14. Prevalence of metabolic syndrome in patients with minor beta thalassemia and its related factors: a cross-sectional study

    OpenAIRE

    Gozashti, Mohammad Hossein; Hasanzadeh, Ali; Mashrouteh, Mahdieh

    2014-01-01

    Background Atherosclerotic disorders, hypertension and lipid profile alterations are of a lower prevalence in patients with minor beta thalassemia. On the other hand, nowadays, metabolic syndrome is considered as one of the major risk factors of developing cardiovascular diseases. Therefore, the present study was performed to determine the prevalence of metabolic syndrome in patients with minor beta thalassemia. Methods In this case-control study, body length, weight and waist circumference, ...

  15. Longitudinal study on thyroid function in patients with thalassemia major: High incidence of central hypothyroidism by 18 years

    OpenAIRE

    Soliman, Ashraf T.; Fawzia Al Yafei; Lolwa Al-Naimi; Noora Almarri; Aml Sabt; Mohamed Yassin; Vincenzo De Sanctis

    2013-01-01

    Introduction: Primary hypothyroidism is one of the most frequent complications observed in-patients suffering from thalassemia. We investigated and reviewed the thyroid function in all thalassemic patients attending the Pediatric Endocrine Clinic of Hamad Medical Center, Doha, Qatar during the last 10 years of follow-up. Patients and Methods: A total of 48 patients with ί-thalassemia major between 5 years and 18 years of age. Thyroid dysfunction was defined as follows: Overt hypothyroidism (l...

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

    Science.gov (United States)

    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.

  17. Posterior transverse interarch discrepancy on HbE β thalassemia patients

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    Yuniar Zen

    2011-03-01

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

  18. Changes in the quality of life of people with thalassemia major between 2001 and 2009

    Directory of Open Access Journals (Sweden)

    Gollo G

    2013-03-01

    Full Text Available Giorgia Gollo,1 Gaia Savioli,2 Manuela Balocco,2 Cristina Venturino,3 Elio Boeri,4 Massimo Costantini,1 Gian Luca Forni21Regional Palliative Care Network, IRCCS AOU San Martino-IST, Genoa; 2Hematology, Center for Thalassemia, Galliera Hospital, Genoa, 3Psychiatric Service, Galliera Hospital, Genoa, 4Department of Hematology and Oncology, Gaslini Institute, Genoa, Italy Background: The prolonged survival of patients with thalassemia major as a result of the novel therapeutic strategies introduced in the last decade makes patient quality of life an important issue. This study investigated the changes occurring in overall quality of life in patients with thalassemia in the last decade.Methods: This was a population-based cross-sectional survey of quality of life in the entire population with thalassemia major resident in the Liguria region of Italy from 2001 to 2009. The self-administered Short Form-36 (SF-36 questionnaire was used to measure quality of life in patients with thalassemia.Results: Forty-nine and 52 eligible patients were assessed in 2001 and 2009, respectively. A total of 43 patients were assessed in both 2001 and 2009. Almost 40% of these 43 patients received deferasirox in 2009, a drug which was not available in 2001. The distribution of ferritin levels was lower in 2009 (median 730 as compared with 2001 (median 1107. Analysis of the raw differences between the two years did not show a significant difference. An improvement was observed in most SF-36 scales in 2009 as compared with 2001, particularly in the Mental Health scale (mean difference in Z score +4.0; 95% confidence interval 0.4–7.5; P = 0.030 and in the Mental Component Summary scale (mean difference in Z score +3.2; 95% confidence interval 0.2–6.2; P = 0.039.Conclusion: The challenge associated with new therapies and improvement in mental quality of life dimensions indicates that implementation of effective interventions for screening and evaluation of quality of

  19. ATLAS electromagnetic end-cap detector

    CERN Multimedia

    Maximilien Brice

    2003-01-01

    After the insertion of the first end-cap into this cryostat, the team proceed to the wiring operations. Millions of wires are connected to the electromagnetic calorimeter on this end-cap, whch must be carefully fed out from the detector so that data can be read out. The energy of photons, electrons and positrons will be measured as they pass through the end-cap having been created along the line of the beams in the proton-proton collisions.

  20. Alpha chain hemoglobins with electrophoretic mobility similar to that of hemoglobin S in a newborn screening program

    Directory of Open Access Journals (Sweden)

    Marcilene Rezende Silva

    2013-01-01

    Full Text Available OBJECTIVE: To characterize alpha-chain variant hemoglobins with electric mobility similar to that of hemoglobin S in a newborn screening program. METHODS: βS allele and alpha-thalassemia deletions were investigated in 14 children who had undefined hemoglobin at birth and an electrophoretic profile similar to that of hemoglobin S when they were six months old. Gene sequencing and restriction enzymes (DdeI, BsaJI, NlaIV, Bsu36I and TaqI were used to identify hemoglobins. Clinical and hematological data were obtained from children who attended scheduled medical visits. RESULTS: The following alpha chain variants were found: seven children with hemoglobin Hasharon [alpha2 47(CE5 Asp>His, HbA2:c.142G>C], all associated with alpha-thalassemia, five with hemoglobin Ottawa [alpha1 15(A13 Gly>Arg, HBA1:c.46G>C], one with hemoglobin St Luke's [alpha1 95(G2 Pro>Arg, HBA1:c.287C>G] and another one with hemoglobin Etobicoke [alpha212 84(F5 Ser>Arg, HBA212:c.255C>G]. Two associations with hemoglobin S were found: one with hemoglobin Ottawa and one with hemoglobin St Luke's. The mutation underlying hemoglobin Etobicoke was located in a hybrid α212 allele in one child. There was no evidence of clinically relevant hemoglobins detected in this study. CONCLUSION: Apparently these are the first cases of hemoglobin Ottawa, St Luke's, Etobicoke and the α212 gene described in Brazil. The hemoglobins detected in this study may lead to false diagnosis of sickle cell trait or sickle cell disease when only isoelectric focusing is used in neonatal screening. Additional tests are necessary for the correct identification of hemoglobin variants.

  1. β-thalassemias: paradigmatic diseases for scientific discoveries and development of innovative therapies.

    Science.gov (United States)

    Rivella, Stefano

    2015-04-01

    β-thalassemias are monogenic disorders characterized by defective synthesis of the β-globin chain, one of the major components of adult hemoglobin. A large number of mutations in the β-globin gene or its regulatory elements have been associated with β-thalassemias. Due to the complexity of the regulation of the β-globin gene and the role of red cells in many physiological processes, patients can manifest a large spectrum of phenotypes, and clinical requirements vary from patient to patient. It is important to consider the major differences in the light of potential novel therapeutics. This review summarizes the main discoveries and mechanisms associated with the synthesis of β-globin and abnormal erythropoiesis, as well as current and novel therapies.

  2. Amelogenesis Imperfecta with Taurodontism, Microdontia, and Minor Thalassemia: A Case Report

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    Fatemeh Mazhari

    2013-12-01

    Full Text Available Amelogenesis imperfecta is a group of genetic disorders that affects both the morphology and quality of tooth structure. Although the disease entity is primarily associated with abnormalities of dental and oral structures, it has been reported to be associated with a few syndromes. A 9-year-old girl with minor thalassemia referred to the Department of Pediatric Dentistry of the Mashhad Faculty of Dentistry with a complaint of sensitivity of first permanent molars. Dental findings consisted of amelogenesis imperfecta, microdontia, posterior cross bite and taurodontism. This is the first report of thalassemia accompanied with amelogenesis imperfecta. Although the patients often are non-symptomatic, the trait can be passed on to a child and if both parents carry the trait, the child could develop a more severe form of the disease; therefore, early diagnosis is important.

  3. Apolipoprotein E4 allele and the risk of left ventricular dysfunction in thalassemia major

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    M Bazrgar

    2007-07-01

    Full Text Available Background: Left ventricular (LV failure is the main cause of death in thalassemia. Iron overload in thesepatients leads to formation of oxygen free radicals. Apolipoprotein (ApoE E4 allele is the least efficient inoxidative stress condition compared with apoE2 and apoE3 alleles. This study was performed to determinethe association of three different ApoE alleles with LV dysfunction in thalassemia major patients in southernIran.Methods: The present study comprised 202 patients with thalassemia major divided into three groups accordingto echocardiographic findings: Group 1 (n=135 had no cardiac impairment; Group 2 (n=38 exhibitedLV dilatation but normal LV systolic function and Group 3 (n=29 showed LV systolic dysfunction.DNA was obtained from all patients and 198 healthy control subjects for ApoE genotyping.Results: Frequency of both apoE3/E4 genotype and apoE4 allele in Group 3 were higher than the controlgroup with corresponding values of P<0.05, Odds Ratio=2.97, 1.06<8.32 and P<0.01, OR=3.01,1.15<7.69, respectively and confidence Interval of 95%. There were no differences observed betweencontrols and patient groups in relation to other genotype and allele frequencies. Interventricular septumthickness and LV end diastolic diameter in apoE4/- patients were more than those of apoE3/E3 patients.Conclusion: ApoE4 allele increases the risk of LV impairment in thalassemia major.

  4. Thalassemia paravertebral tumors and bone marrow scan; Thalassemies, tumeurs paravertebrales et scintigraphie medullaire

    Energy Technology Data Exchange (ETDEWEB)

    Huglo, D.; Rose, C.; Deveaux, M.; Bauters, F.; Marchandise, X. [Centre Hospitalier Universitaire, 59 - Lille (France)

    1995-12-01

    Two first cousins with thalassemia and with a paravertebral mass had had an indium 111 chloride bone marrow scan. Result of scan influenced therapy: medical treatment in one case where an extramedullary erythropoiesis was confirmed, surgical treatment in the other case. The use of dual-isotope SPECT (indium 111 chloride, HDP{sup -99}Tc) constitutes a contribution to the establishment of diagnosis of extramedullary erythropoiesis, giving to bone marrow scintigraphy a merited importance, avoiding the biopsy. (authors). 15 refs., 5 figs.

  5. The epidemiologic transition of thalassemia and associated hemoglobinopathies in southern Taiwan.

    Science.gov (United States)

    Wang, Hui-Ching; Hsieh, Li-Ling; Liu, Yi-Chang; Hsiao, Hui-Hua; Lin, Shu-Kai; Tsai, Wen-Chan; Liu, Ta-Chih

    2017-02-01

    Since 1993, following the National Thalassemia Major Prevention Program and an increase in immigration and interracial marriages, especially in southern Taiwan, the distribution of hemoglobinopathies may have changed. This study investigates the epidemiologic transition of hemoglobinopathies. We analyzed 1870 specimens collected between 2003 and 2012 in southern Taiwan, used gap-polymerase chain reaction and PCR-restriction fragment length polymorphism-based methods, and confirmed genotypes of hemoglobinopathies by DNA sequencing. We found a 91% reduction in the incidence of thalassemia major compared with samples from between 1986 and 1995. The most common genotypes of α-thalassemia and α Hb variants were the SEA type (69.4%) and Hb Quong Sze (1.54%). The most common genotypes of β-thalassemia and β Hb variants were IVS-II-654 (46.2%) and Hb E (2.2%), respectively. Compared with studies performed in different areas of and time intervals in Taiwan, a higher prevalence of -α(3.7), Hb Quong Sze, and Hb E and a lower prevalence of the SEA type were found in this study. However, the SEA type remained the most common genotype observed. In addition, an increasing number of cases with an -α(3.7) type carrier, Hb Quong Sze carrier, and G(γ)(A(γ)δβ)° were identified following a peak of interracial marriages between 2003 and 2005, reflecting a regional difference and the impact of interracial marriage. In conclusion, global migration and international marriage have changed the distribution of hemoglobinopathies in Taiwan. A more comprehensive prenatal screening for new immigrants with a longer follow-up is warranted.

  6. Multiple transfused thalassemia major: Ocular manifestations in a hospital-based population

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    Taneja Rashi

    2010-01-01

    Full Text Available Purpose: To study the ocular manifestations in multiple transfused beta-thalassemia major patients and assess the ocular side-effects of iron chelating agents. Materials and Methods: In this prospective observational study, 45 multiple transfused beta-thalassemia major children between six months and 21 years of age were enrolled and assigned groups according to the treatment regimens suggested. Group A received only blood transfusions, Group B blood transfusions with subcutaneous desferrioxamine, Group C blood transfusions with desferrioxamine and oral deferriprone and Group D blood transfusions with deferriprone. Ocular status at the time of enrolment was documented. Subjects were observed quarterly for one year for changes in ocular status arising due to the disease process and due to iron chelation therapy. Children with hemoglobinopathies other than beta-thalassemia major, congenital ocular anomalies and anemia due to other causes were excluded. Results: Ocular involvement was observed in 58% of patients. Lenticular opacities were the most common ocular finding (44%, followed by decreased visual acuity (33%. An increased occurrence of ocular changes was observed with increase of serum ferritin and serum iron levels as well as with higher number of blood transfusions received. Desferrioxamine seemed to have a protective influence on retinal pigment epithelium (RPE mottling. Occurrence of lenticular opacities and RPE degeneration correlated positively with use of desferrioxamine and deferriprone respectively. Follow-up of patients for one year did not reveal any change in ocular status. Conclusion: Regular ocular examinations can aid in preventing, delaying or ameliorating the ocular complications of thalassemia.

  7. Extramedullary hematopoiesis is associated with lower cardiac iron loading in chronically transfused thalassemia patients.

    Science.gov (United States)

    Ricchi, Paolo; Meloni, Antonella; Spasiano, Anna; Neri, Maria Giovanna; Gamberini, Maria Rita; Cuccia, Liana; Caruso, Vincenzo; Gerardi, Calogera; D'Ascola, Domenico Giuseppe; Rosso, Rosamaria; Campisi, Saveria; Rizzo, Michele; Terrazzino, Fabrizia; Vangosa, Alessandra Briatico; Chiodi, Elisabetta; Missere, Massimiliano; Mangione, Maurizio; Positano, Vincenzo; Pepe, Alessia

    2015-11-01

    The aim of this study was to evaluate, in a large cohort of chronically transfused patients, whether the presence of extramedullary hematopoiesis (EMH) accounts for the typical patterns of cardiac iron distribution and/or cardiac function parameters. We retrospectively selected 1,266 thalassemia major patients who had undergone regular transfusions (611 men and 655 women; mean age: 31.3 ± 8.9 years, range: 4.2-66.6 years) and were consecutively enrolled within the Myocardial Iron Overload in Thalassemia network. The presence of EMH was evaluated based on steady-state free precession sequences; cardiac and liver iron overloads were quantified using a multiecho T2* approach; cardiac function parameters and pulmonary diameter were quantified using the steady-state free precession sequences; and myocardial fibrosis was evaluated using the late gadolinium enhancement technique. EMH was detected in 167 (13.2%) patients. The EMH+ patients had significantly lower cardiac iron overload than that of the EMH- patients (P = 0.003). The patterns of cardiac iron distribution were significantly different in the EMH+ and EMH- patients (P < 0.0001), with a higher prevalence of patients with no myocardial iron overload and heterogeneous myocardial iron overload and no significant global heart iron in the EMH+ group EMH+ patients had a significantly higher left ventricle mass index (P = 0.001) and a significantly higher pulmonary artery diameter (P = 0.002). In conclusion, in regularly transfused thalassemia patients, EMH was common and was associated with a thalassemia intermedia-like pattern of cardiac iron deposition despite regular transfusion therapy.

  8. Estimated red blood cell thickness in microcytic anemia due to iron deficiency anemia and thalassemia

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    Viroj Wiwanitkit

    2009-05-01

    Full Text Available "nAnemia is one of the most common hematological disorders that are still the present in all countries around the world. Microcytic anemia is a specific kind of anemia presenting with small red blood cell. In this paper, the author discusses on the estimated red blood cell thickness, a new proposed parameter, comparing between that of iron deficiency anemia and thalassemia and further extrapolate on the clinical implication.

  9. Development and recent progresses of gene therapy for β-thalassemia

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    Santina Acuto

    2014-09-01

    Full Text Available β-thalassemias are among the most common inherited monogenic disorders worldwide due to mutations in the β-globin gene that reduce or abolish the production of the β-globin chain resulting in transfusion-dependent chronic anemia. Currently, the only curative treatment is allogeneic hematopoietic stem cells (HSCs transplantation, but this option is limited by the a vailability of HLA-matched donor. Gene therapy, based on autologous transplantation of genetically corrected HSCs, holds the promise to treat patients lacking a compati ble bone marrow donor. I nit ial attempts of gene transfer have been unsuccessful due to limitations of available vectors to stably transfer a globin gene in HSCs and reach high and regulated expression in the erythroid progeny. With the advent of lentiviral vectors (LVs, based on human immunodeficiency virus, many of the initial limitations have been overcome. Since 2000 when Sadelain and co-workers first demonstrated successful globin gene transfer in murine thalassemia models with improvement of the phenotype using a recombinant β globin/LV, several other groups have developed different vectors encoding either β, γ or mutated globin genes and confirmed these results in both murine models and erythroid progeny derived from patient’s HSCs. In light of these encouraging results, research has recently moved into clinical trials that are ongoing or soon to begin. One participant in an ongoing gene transfer trial for β-thalassemia has achieved clinical benefit with elimination of his transfusi on re quirement. Here , dev elopmen t and recent progress of gene therapy for β-thalassemia is reviewed.

  10. HAEMOGLOBIN E/ BETA - THALASSEMIA: A CASE REPORT FROM UPPER ASSAM, INDIA

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    Anju Barhai Teli

    2015-02-01

    Full Text Available We report here a patient from upper Assam region of India with Hb E / β thalassemia disease, whose father belongs to the tea garden community and mother is Assamese where Hb E is very common. The patient was suffering from severe anaemia and hepatosplenomegaly. After examination two units of blood transfusion and folic acid course were given to the patient. Patient was finally treated with c helation therapy

  11. LONGITUDINAL STUDY ON LIVER FUNCTIONS IN PATIENTS WITH THALASSEMIA MAJOR BEFORE AND AFTER DEFERASIROX (DFX) THERAPY

    OpenAIRE

    Ashraf Tawfik Soliman; Mohamed Yassin; Fawzia AlYafei; Lolwa Al-Naimi; Noora Almarri; Aml Sabt; Vincenzo De Sanctis

    2014-01-01

    With regular blood transfusion and iron chelation therapy, most patients with thalassemia major (BTM) now survive beyond the third decade of life . Liver disease is becoming an important cause of morbidity and mortality in these patients. Chronic hepatitis and/or severe iron overload are important causes of liver pathology. Iron chelation with desferrioxamine (Desferal)  reduces excessive body iron, but its efficacy is limited by poor compliance and dose related toxicity. The recent use of De...

  12. Longitudinal Study on Liver Functions in Patients with Thalassemia Major before and after Deferasirox (DFX) Therapy

    OpenAIRE

    SOLIMAN, Ashraf; Yassin, Mohamed; Al Yafei, Fawzia; Al-Naimi, Lolwa; Almarri, Noora; Sabt, Aml; De Sanctis, Vincenzo

    2014-01-01

    By performing regular blood transfusion and iron chelation therapy, most patients with beta thalassemia major (BTM) now survive beyond the third decade of life. Liver disease is becoming an important cause of morbidity and mortality in these patients. Chronic hepatitis and/or severe iron overload are both important causes of liver pathology. Iron chelation with desferrioxamine (DFO) reduces excessive body iron, but its efficacy is limited by poor compliance and dose related toxicity. The rece...

  13. Population Screening and Prevention Strategies for Thalassemias and other Hemoglobinopathies of Eastern India: Experience of 18,166 cases.

    Science.gov (United States)

    Chatterjee, Tridip; Chakravarty, Amit; Chakravarty, Sudipa

    2015-01-01

    We evaluated population screening programs (1999-2011), conducted by the Thalassaemia Foundation, Kolkata, India, for the first time in Eastern India in different districts of West Bengal, for prevention of thalassemia comprising screening of heterozygotes and β-thalassemia intermedia (β-TI) cases [β(+), β(++), β(0)/β(+), β(E)/β(E) (codon 26 or HBB: c.79G > A), Hb-E-β-thalassemia (Hb E-β-thal)]. Among 18,166 cases, we found 2092 heterozygotes and 2245 β-TI individuals (who had no information about their disorders). Results were evaluated with standard hematological analyses including erythrocyte indices, hemoglobin (Hb) typing and quantification. Participants were divided into five groups (children, pre-marriage cases, pre-pregnancy cases, affected family members, pregnant women). The objectives of this evaluation were to fix cut-off values of red blood cells (RBCs), mean corpuscular volume (MCV), mean corpuscular Hb (MCH), red blood cell distribution width (RDW) and Hb A2, as the standard World Health Organization (WHO) guidelines were not strictly followed in mass-scale screening programs. We have observed many dilemmas in considering the status of the thalassemia subject, due to presence of some other clinical conditions such as iron deficiency anemia, α-thalassemia (α-thal), δ-thalassemia (δ-thal), clinically silent Hb variants, and some cases of non hemoglobinopathies (such as pregnancy) along with thalassemia. The MCV values varied greatly in different conditions of hemoglobinopathies, whereas MCH provided a more stable measurement. We found an MCH value of <27.0 pg is a suitable cut-off point for screening in this population. Participants with an MCH of <27.0 pg should be investigated further to confirm or exclude a diagnosis of β-thal trait.

  14. Synthesis, Characterization, and Tribological Behavior of Oleic Acid Capped Graphene Oxide

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    Tiedan Chen

    2014-01-01

    Full Text Available Graphene oxide (GO nanosheets were prepared by modified Hummers and Offeman methods. Furthermore, oleic acid (OA capped graphene oxide (OACGO nanosheets were prepared and characterized by means of Fourier transform-infrared spectroscopy (FT-IR, transmission electron microscopy (TEM, and X-ray diffraction (XRD. At the same time, the friction and wear properties of OA capped graphite powder (OACG, OACGO, and oleic acid capped precipitate of graphite (OACPG as additives in poly-alpha-olefin (PAO were compared using four-ball tester and SRV-1 reciprocating ball-on-disc friction and wear tester. By the addition of OACGO to PAO, the antiwear ability was improved and the friction coefficient was decreased. Also, the tribological mechanism of the GO was investigated.

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

    Science.gov (United States)

    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.

  16. [Neonatal expression of beta-thalassemia trait associated with hereditary spherocytosis in two monozygotic twins].

    Science.gov (United States)

    Ben Hamouda, H; Mahjoub, B; Soua, H; Laradi, S; Miled, A; Sfar, M T

    2017-02-01

    The beta-thalassemia trait is a heterozygous beta-thalassemia characterized by a partial deficiency of the synthesis of beta-globin chains of hemoglobin. It is usually asymptomatic and the diagnosis is often made on the occasion of the completion of a systematic blood count or a family survey. Clinical expression during the neonatal period is impossible and its association with hereditary spherocytosis is common. We report two monozygotic twins who, on the 3rd day of life, presented intense jaundice, unconjugated bilirubin associated with anemia, without hepatosplenomegaly. Laboratory tests found nonimmune hemolytic anemia with microcytosis and hypochromia justifying iterative blood transfusions. The etiological investigation found heterozygous beta-thalassemia associated with hereditary spherocytosis. The family investigation and molecular analysis objectified the beta-thalassemic mutation IVS1nt110 (G→A) in the heterozygous state in the twins, the father, the mother, and in one of the two brothers. With any nonimmune hemolytic anemia in newborns, the etiological investigation should be systematic for early diagnosis and to plan appropriate treatment.

  17. Prognostic factors in bone marrow transplantation for beta thalassemia major: experiences from Iran.

    Science.gov (United States)

    Ghavamzadeh, A; Nasseri, P; Eshraghian, M R; Jahani, M; Baybordi, I; Nateghi, J; Khodabandeh, A; Sadjadi, A R; Mohyeddin, M; Khademi, Y

    1998-12-01

    This study concerns the effects of several pre-transplant features on outcome for patients with beta thalassemia major who underwent bone marrow transplantation (BMT). Seventy patients with beta thalassemia major underwent bone marrow transplantation during the period 1991-1997 in Shariati Hospital in Tehran, Iran. The survival and rejection curves levelled off at 8 and 18 months after transplantation at 82.6% and 11.4%, respectively. Pre-transplant clinical features (age, serum ferritin, portal fibrosis, hepatomegaly and quality of chelation therapy) were examined for their effects on survival and recurrence of thalassemia in this group of patients who were less than 16 years old. Increasing age, presence of portal fibrosis and increasing serum ferritin were significantly associated with reduced probability of survival (P = 0.0047, P = 0.016 and P = 0.024, respectively). Hepatomegaly and inadequate pre-transplant chelation therapy which were documented as poor prognostic factors in previous studies, were not evaluable in this study. We also showed the benefits of transplanting more than 5.5 x 10(8)/kg cells in this group of patients with no increase in complications.

  18. Analysis of Fetal Blood: Is There Still a Role for Prenatal Diagnosis of Thalassemia?

    Science.gov (United States)

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

    2016-01-01

    The aim of the present study was to report the use of analysis of fetal blood in prenatal diagnosis (PND) of β- and α-thalassemia (β- and α-thal), at a Chinese tertiary, maternity center. All cases undergoing invasive testing for PND of thalassemias from 1 January 2010 to 31 December 2014 were included. The main clinical characteristics of these invasive procedures were retrieved from the database software used for analysis. One thousand, nine hundred and six invasive PNDs were carried out for thalassemia, including 904 cases for β-thal and 1002 for α-thal. In the 904 PNDs for β-thal, chorionic villus sampling (CVS) was done in 321 cases and amniocentesis in 583 cases. No fetal blood analysis was used for cases at-risk for β-thal. In the 1002 PNDs for α-thal, CVS was done in 724 cases, amniocentesis in 137 cases and fetal blood analysis in 141 cases. All the 278 cases sampled by amniocentesis or fetal blood analysis were found to be affected by Hb Bart's (γ4) disease. Currently, fetal blood analysis is considered only in relatively late gestation when Hb Bart's disease has already been identified by ultrasound in a fetus at-risk for α-thal.

  19. Talassemia β intermediária em gestante Intermediate β thalassemia in a pregnant woman

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    Tatiana M. Sakamoto

    2008-12-01

    Full Text Available A talassemia β é a forma considerada clinicamente a mais importante dentre as talassemias, em virtude do grau de morbidade e mortalidade, em consequência da anemia hemolítica. O presente relato de caso refere-se a uma gestante portadora da talassemia β intermediária, identificada em programa de rastreamento de anemia hemolítica e tem como objetivo demonstrar a importância do diagnóstico precoce e adequado de uma anemia hereditária, durante o pré-natal. Ressalta também a necessidade de orientação aos portadores em relação aos seus descendentes e a eficiência do acompanhamento por uma equipe multidisciplinar especializada.β-thalassemia is clinically the most important form of thalassemia due to its high level of morbidity and mortality as a result of intense hemolytic anemia. The present case report describes the case a pregnant woman who is an intermediate β-thalassemia carrier identified in a screening program for hemolytic anemia. This work aims at showing the importance of correct and early diagnosis of inherited anemia during pregnancy. It also stresses the need of guidance for carriers in respect to their progeny and discusses the efficiency of follow ups by a multidisciplinary team during pregnancy.

  20. Genetic diversity of HCV among various high risk populations (IDAs, thalassemia, hemophilia, HD patients) in Iran

    Institute of Scientific and Technical Information of China (English)

    Rafiei A; Darzyani Azizi M; Taheri S; Haghshenas MR; Hosseinian A; Makhlough A

    2013-01-01

    Objective: To determine the patterns of distribution of HCV genotypes among high risk population in north of Iran. Methods: A cross-sectional study was conducted on 135 HCV RNA-positive high risk individuals including thalassemia, hemophilia, patients under hemodialysis and intravenous drug addicts. HCV genotypes were determined based on amplification with type-specific primers methods. Results: Among the 187 anti-HCV positive samples, only 135 (72.2%) gave HCV-RNA positvity. Over all, the most identified HCV type was genotype 3a (51.1%) followed by 1a (27.4%), 1b (8.2%). Sixteen (11.9%) out of 135 HCV RNA-positive participants have infected with more than one genotype or subtypes as follow; 1a/1b in 11 (8.2%), 2/3a in 3 (2.2%), and 1a/1b/3a in 2 (1.5%). Stratification of participants revealed that HCV subtype 3a was more prominent in thalassemia, hemophilia and HD patients but 1a and 1b were frequent in intravenous drug addicts. Conclusions: This study is the first report on HCV genotypes among Iranian subjects with different exposure categories resided in Mazandaran, where genotype 3a was found to be the most frequent genotype in thalassemia, hemophilia, and hemodialysis patients but not in IDAs. Since the addiction age is decreasing in Iran and a lot of addicts are IDAs, it might change the subtype pattern of HCV in general population.

  1. Vascular dysfunction in patients with young β-thalassemia: relation to cardiovascular complications and subclinical atherosclerosis.

    Science.gov (United States)

    Adly, Amira Abdel Moneam; El-Sherif, Nayera Hazaa; Ismail, Eman Abdel Rahman; El-Zaher, Yosra Abd; Farouk, Amal; El-Refaey, Asmaa Mohamed; Wahba, Mohammed Samy

    2015-11-01

    We aimed to study the endothelial dysfunction among children and adolescents with transfusion-dependent β-thalassemia using von Willebrand factor antigen (VWF:Ag) and flow cytometric analysis of circulating CD144(+) endothelial microparticles (EMPs) and endothelial progenitor cells (CD34(+)VEGFR2(+)) and assess their relation to iron overload, erythropoietin and chelation therapy as well as echocardiographic parameters and carotid intima-media thickness. The VWF:Ag, EMPs, and CD34(+)VEGFR2(+) cells were significantly higher among patients with β-thalassemia than controls (P < .001). The type of chelation and patients' compliance did not influence the results. No significant correlations were found between the studied vascular markers. Patients with evident heart disease had higher VWF: Ag, EMPs, and CD34(+)VEGFR2(+) cells than those without. Carotid intima-media thickness was increased among patients but not correlated with vascular markers. We suggest that procoagulant EMPs and VWF: Ag are involved in cardiovascular complications in patients with young β-thalassemia. CD34(+)VEGFR2(+) cells were further increased in response to tissue injury contributing to reendothelialization and neovascularization.

  2. Hemoglobinopathies and thalassemia screening among Senoi Orang Asli in Peninsular Malaysia

    Science.gov (United States)

    Rong, Danny Koh Xuan; Ismail, Endom; Sabudin, Raja Zahratul Azma Raja; Hussin, Noor Hamidah; Othman, Ainoon

    2015-09-01

    Orang Asli are the minority indigenous people in Peninsular Malaysia and can be divided into 3 main groups (Negrito, Senoi and Proto Malay) with different six sub-ethnics under each group. Within the Senoi group, the six sub-ethnics are sub-ethnic Mah Meri, Semoq Beri, Che Wong, Jah Hut, Semai and Temiar. This study was aimed to investigate the current prevalence of α- and β-thalassemia and hemoglobinopathies and their mutation types among all six sub-ethnics of Senoi Orang Asli. Blood samples from 685 Senoi participants were collected and sent immediately for routine full blood count analysis and hemoglobin sub-typing. Of 378 subjects screened, 7 subjects were found to be Hemoglobin E (HbE) beta thalassemia carriers, 13 beta thalassaemic, 35 Hemoglobin Constant Spring (HbCS) carriers, 6 compound HbE and HbCS carriers, 32 with HbE disease and 163 HbE heterozygote carriers. The findings of high HbE among Temiars and Jah Huts and high HbCS exclusively in Jah Huts in this study suggest distinct differences across sub-ethnics under Senoi group. Understanding of prevalence and wide spectrum of thalassemia and hemoglobinopathies among Senoi and Orang Asli is essential for national thalassaemia awareness and prevention program, especially in Orang Asli communities.

  3. Reducing TMPRSS6 ameliorates hemochromatosis and β-thalassemia in mice.

    Science.gov (United States)

    Guo, Shuling; Casu, Carla; Gardenghi, Sara; Booten, Sheri; Aghajan, Mariam; Peralta, Raechel; Watt, Andy; Freier, Sue; Monia, Brett P; Rivella, Stefano

    2013-04-01

    β-Thalassemia and HFE-related hemochromatosis are 2 of the most frequently inherited disorders worldwide. Both disorders are characterized by low levels of hepcidin (HAMP), the hormone that regulates iron absorption. As a consequence, patients affected by these disorders exhibit iron overload, which is the main cause of morbidity and mortality. HAMP expression is controlled by activation of the SMAD1,5,8/SMAD4 complex. TMPRSS6 is a serine protease that reduces SMAD activation and blocks HAMP expression. We identified second generation antisense oligonucleotides (ASOs) targeting mouse Tmprss6. ASO treatment in mice affected by hemochromatosis (Hfe(-/-)) significantly decreased serum iron, transferrin saturation and liver iron accumulation. Furthermore, ASO treatment of mice affected by β-thalassemia (HBB(th3/+) mice, referred to hereafter as th3/+ mice) decreased the formation of insoluble membrane-bound globins, ROS, and apoptosis, and improved anemia. These animals also exhibited lower erythropoietin levels, a significant amelioration of ineffective erythropoiesis (IE) and splenomegaly, and an increase in total hemoglobin levels. These data suggest that ASOs targeting Tmprss6 could be beneficial in individuals with hemochromatosis, β-thalassemia, and related disorders.

  4. Decreased differentiation of erythroid cells exacerbates ineffective erythropoiesis in beta-thalassemia.

    Science.gov (United States)

    Libani, Ilaria V; Guy, Ella C; Melchiori, Luca; Schiro, Raffaella; Ramos, Pedro; Breda, Laura; Scholzen, Thomas; Chadburn, Amy; Liu, YiFang; Kernbach, Margrit; Baron-Lühr, Bettina; Porotto, Matteo; de Sousa, Maria; Rachmilewitz, Eliezer A; Hood, John D; Cappellini, M Domenica; Giardina, Patricia J; Grady, Robert W; Gerdes, Johannes; Rivella, Stefano

    2008-08-01

    In beta-thalassemia, the mechanism driving ineffective erythropoiesis (IE) is insufficiently understood. We analyzed mice affected by beta-thalassemia and observed, unexpectedly, a relatively small increase in apoptosis of their erythroid cells compared with healthy mice. Therefore, we sought to determine whether IE could also be characterized by limited erythroid cell differentiation. In thalassemic mice, we observed that a greater than normal percentage of erythroid cells was in S-phase, exhibiting an erythroblast-like morphology. Thalassemic cells were associated with expression of cell cycle-promoting genes such as EpoR, Jak2, Cyclin-A, Cdk2, and Ki-67 and the antiapoptotic protein Bcl-X(L). The cells also differentiated less than normal erythroid ones in vitro. To investigate whether Jak2 could be responsible for the limited cell differentiation, we administered a Jak2 inhibitor, TG101209, to healthy and thalassemic mice. Exposure to TG101209 dramatically decreased the spleen size but also affected anemia. Although our data do not exclude a role for apoptosis in IE, we propose that expansion of the erythroid pool followed by limited cell differentiation exacerbates IE in thalassemia. In addition, these results suggest that use of Jak2 inhibitors has the potential to profoundly change the management of this disorder.

  5. Abdominal Ultrasonographic Findings in Beta Thalassemia Major Patients in North of Iran

    Directory of Open Access Journals (Sweden)

    R. Abdi

    2007-05-01

    Full Text Available Background and Objective: High prevalence of tha-lassemia in the North of Iran is a major challenge of medical practitioners in this area. To investigate the prevalence of abdominal ultrasound findings in these patients, the present study was conducted. Materials and Methods: Two hundred patients (92 girls and 108 boys, all suffering from Beta thalas-semia major with a mean age of 14.5 years (ranging from 5 to 34 years were included in the study. Ab-dominal ultrasound examination was performed by two radiologists between 2001 and 2005 to detect sonographic findings in these patients. Results: Hepatomegaly was presented in 75% of these patients and splenomegaly was detected in 46% of them while 45% of cases had undergone splenec-tomy. Total incidence of gall bladder stone formation was 14% (15.5% in females and 11.9% in males and it had a direct correlation with the patients’ age. Lymphadenopathy of portohepatic and celiac area was detected in 138 (68% patients. In 4 patients ul-trasound revealed portal vein thrombosis whereas in the other 4 cases, splenic extramedullary hematopoi-esis was detected. Conclusion: This study revealed that a remarkable portion of patients had developed these complica-tions. Authors suggest ultrasound to be a part of rou-tine examinations in beta thalassemia major patients who receive multiple transfusions.

  6. STUDY OF PALMAR DERMATOGLYPHICS PATTERN CHANGES IN β-THALASSEMIA MAJOR PATIENTS

    Directory of Open Access Journals (Sweden)

    Debjyoti

    2016-04-01

    Full Text Available Palmar dermatoglyphics pattern in β-Thalassemia major patients and in normal subjects were studied to find out any statistically significant changes if present. SETTING AND DESIGN Qualitative and quantitative changes in the pattern may be present, as these patterns are genetically determined. BACKGROUND β-Thalassemia major is a serious and prevalent form of haemoglobin disorder in these regions with autosomal recessive pattern of inheritance. Study of population by applying different tools is an important aspect of prevention. Dermatoglyphics study may be helpful to know the phenotypic trait of the individual. METHODS AND MATERIALS 50 diagnosed cases of β-thalassemia major and the equal number of matched control group of either sex were included in the investigation. Palmar imprints were taken by traditional paper and ink method. STATISTICAL ANALYSIS Chi square test and t- test were used. RESULTS AND CONCLUSION Arch, loop and whorl’s character, a-b ridge counts and ‘atd’ angles were studied. Significant rise in number of whorls and changes in ‘atd’ angles were detected in the cases. This information may be useful in population genetics study, though more detail research is needed.

  7. Molecular Scanning of β-Thalassemia in the Southern Region of Central Java, Indonesia; a Step Towards a Local Prevention Program.

    Science.gov (United States)

    Rujito, Lantip; Basalamah, Muhammad; Mulatsih, Sri; Sofro, Abdul Salam M

    2015-01-01

    Thalassemia is the most prevalent genetic blood disorder worldwide, and particularly prevalent in Indonesia. The purpose of this study was to determine the spectrum of β-thalassemia (β-thal) mutations found in the southern region of Central Java, Indonesia. The subjects of the study included 209 β-thal Javanese patients from Banyumas Residency, a southwest region of Central Java Province. DNA analysis was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), amplification refractory mutation system (ARMS), and the direct sequencing method. The results showed that 14 alleles were found in the following order: IVS-I-5 (G > C) (HBB: c.92 + 5G > C) 43.5%, codon 26 (Hb E; HBB: c.79G > A) 28.2%, IVS-I-1 (G > A) (HBB: c.92 + 1G > A) 5.0%, codon 15 (TGG > TAG) (HBB: c.47G > A) 3.8%, IVS-I-1 (G > T) (HBB: c.92 + 1G > T) 3.1%, codon 35 (-C) (HBB: c.110delC) 2.4%. The rest, including codons 41/42 (-TTCT) (HBB: c.126_129delCTTT), codons 8/9 (+G) (HBB: c.27_28insG), codon 19 (AAC > AGC) (HBB: c.59A > G), codon 17 (AAG > TAG) (HBB: c.52A > T), IVS-I-2 (T > C) (HBB: c.92 + 2T > C), codons 123/124/125 (-ACCCCACC) (HBB: c.370_378delACCCCACCA), codon 40 (-G) (HBB: c.123delG) and Cap +1 (A > C) (HBB: c.-50A > C), accounted for up to 1.0% each. The most prevalent alleles would be recommended to be used as part of β-thal screening for the Javanese, one of the major ethnic groups in the country.

  8. Nature mangement, landscape and the CAP

    NARCIS (Netherlands)

    Brouwer, F.M.; Godeschalk, F.E.

    2004-01-01

    The integration of nature management, landscape and environmental concerns into the Common Agricultural Policy (CAP) has gained momentum with the CAP reforms adopted in June 2003. The report explores instruments and approaches that contribute to the inte-gration of nature conservation and landscape

  9. ALEPH end-cap and barrel

    CERN Multimedia

    Patrice Loiez

    1993-01-01

    The end-cap is pulled away from the barrel on the ALEPH detector so that the hadronic calorimeter and muon chambers are revealed. The end-cap maximises the data available from particles produced along the direction of the beam. The workers on the inner part of the detector give a sense of scale.

  10. Ferromagnetism of polythiophene-capped Au nanoparticles

    Science.gov (United States)

    Suzuki, K.; Zhang, H.; Saito, K.; Garitaonandia, J. S.; Goikolea, E.; Insausti, M.

    2011-04-01

    The magnetic and electrical transport properties of regioregular poly(3-hexylthiophene)-capped Au nanoparticles (NPs) doped with iodine have been investigated to clarify the effectiveness of conductive polymer capping on the induction of ferromagnetism in Au. The room-temperature magnetization curve of the undoped polythiophene-capped Au NPs exhibits a clear hysteresis behavior with a coercive force of 160 Oe. The spontaneous magnetization normalized by the mass of Au is 2.0 × 10-2 emu/g. The spontaneous magnetization was found virtually unaffected by iodine doping, whereas the electrical conductivity is enhanced dramatically to ˜10 S/cm. Our results show that polythiophene capping could lead to spontaneous magnetic polarization in Au NPs, and the conductivity of the polymer capping does not affect the ferromagnetism of the Au nanoparticles, opening a possibility for further investigation into the magnetotransport behavior of ferromagnetic Au NPs.

  11. Hydroxyurea decreases hospitalizations in pediatric patients with Hb SC and Hb SB+ thalassemia

    Directory of Open Access Journals (Sweden)

    Lebensburger JD

    2015-12-01

    Full Text Available Jeffrey D Lebensburger, Rakeshkumar J Patel, Prasannalaxmi Palabindela, Christina J Bemrich-Stolz, Thomas H Howard, Lee M HilliardDivision of Pediatric Hematology Oncology, University of Alabama at Birmingham, Birmingham, AL, USAPurpose: Patients with hemoglobin SC (Hb SC and hemoglobin SB+ (Hb SB+ thalassemia suffer from frequent hospitalizations yet strong evidence of a clinical benefit of hydroxyurea (HU in this population is lacking. Patients with recurrent hospitalizations for pain crisis are offered HU at our institution based on small cohort data and anecdotal benefit. This study identifies outcomes from a large cohort of patients with Hb SC and SB+ thalassemia who were treated with HU for 2 years.Materials and methods: A retrospective review was conducted of 32 patients with Hb SC and SB+ thalassemia who were treated with HU. We reviewed the number, and reasons for hospitalization in the 2 years prior to, and 2 years post-HU treatment as well as laboratory changes from baseline, over 1 year.Results: Patients with Hb SC and SB+ thalassemia started on HU for frequent pain, had a significant reduction in hospitalizations over 2 years as compared to the 2 years prior to HU initiation (mean total hospitalizations/year: pre-HU: 1.6 vs post-HU 0.4 hospitalizations, P<0.001; mean pain hospitalizations/year: pre-HU 1.5 vs post-HU 0.3 hospitalizations, P<0.001. Patients demonstrated hematologic changes including an increase in percent fetal hemoglobin (%HbF pre–post HU (4.5% to 7.7%, P=0.002, mean corpuscular volume (74 to 86 fL, P<0,0001, and decrease in absolute neutrophil count (5.0 to 3.2×109/L, P=0.007. Patients with higher doses of HU demonstrated the greatest reduction in hospitalizations but this was unrelated to absolute neutrophil count.Conclusion: This cohort of patients with Hb SC and SB+ thalassemia provides additional support for using HU in patients with recurrent hospitalizations for pain. A large randomized multicenter trial of

  12. STUDY OF SERUM HAPTOGLOBIN LEVEL AND ITS RELATION TO ERYTHROPOIETIC ACTIVITY IN BETA THALASSEMIA CHILDREN .

    Directory of Open Access Journals (Sweden)

    Seham Ragab

    2015-02-01

    Full Text Available Background  :Serum haptoglobin (Hp is a reliable marker for hemolysis regardless the inflammatory state.  Objective: We investigated the possible relation between Hp depletion and hemolysis severity, hepatitis C virus (HCV infection and iron load in β-thalassemia children. Methods: Twenty  two β-thalassemia major (TM ,20 β-thalassemia  intermedia (TI children with 20 age and sex matched healthy controls were involved. Pre-transfusion hemoglobin level was considered . Serum ferritin , Hp  and transferrin receptor  levels (sTfR  (by ELISA , alanine aminotransferase (ALT and  aspartate aminotransferase (AST  (by colorimetric method were assayed. Markers of hepatitis C virus  (HCV  were done by PCR. Results:  The mean Hp levels among the studied groups were as follows; 8.02 ± 0.93 (mg/dl , 8.6 ±0.72 (mg/dl  and 122  ± 18.5(mg/dl   for TM ,TI and the controls respectively . Both patient groups had significantly lower Hp level compared to the controls (P<0.0001  with significant lower level in TM compared to TI  children ( P= 0.034  .Significant inverse correlations were  found between serum Hp and sTfR levels in thalassemia children combined and in each group (TM and TI as well as among HCV infected children. STfR   was the only significant independent predictor for  serum Hp level (t= -5.585 , P<0.0001 . Among  HCV infected patients , no significant correlation was found between serum Hp and serum transaminases  .Conclusion:  Serum Hp depletion in thalassemia had significant relation to disease severity and correlated   well with their erythropoietic activity, as assessed by the measurement of  sTfR without significant relation  HCV infection . Large sample  multicenter studies are  recommended.

  13. Prevalence and Intensity of Depression in Mothers of Children with Beta-Thalassemia Major In Talghani Hospital of Gorgan, Iran

    Directory of Open Access Journals (Sweden)

    Nargesbeygom Mirbehbahani

    2014-01-01

    Full Text Available Background: Thalassemia is a chronic disease that it leads to psychological and social problems for parents. Mothers are at markedly increased risk of suffering from psychological distress and depression because they usually take on a considerable part of extra care that their children need.This study was designed to determine prevalence and intensity of depression in mothers with a thalassemic child. Material and Methods: In this cross – sectional study, 65 mothers of children with thalassemia major (case group and 65 mothers of children without thalassemia major (control group were assessed using the Beck Depression Inventory (BDI. Data were analyzed by using SPSS (v 16.0 for windows. Results: Prevalence of depression was significantly higher in case group than that in control group (84.6%vs. 56.9%, p <0.05. Moderate depression had a highest prevalence in the both groups (33.4% in case group and 30.8% in control group. Prevalence of severe depression in case group was markedly higher than that in control group (29.2% vs. 3.1% p<0.05. There was a significant difference between intensity of depression in mothers of case group that had another child with beta-thalassemia major (p<0.05. Conclusion: Mothers of children with thalassemia major are vulnerable to depression. They need psychosocial support to promote their health.

  14. Valores de ferritina sérica em beta talassemia heterozigota Serum ferritin levels in beta thalassemia carrier

    Directory of Open Access Journals (Sweden)

    Isabeth F. Estevão

    2010-01-01

    Full Text Available A low iron level, the commonest nutritional deficiency in the world, is a public health problem in developing countries. On the other hand, an excessive amount of iron is toxic, causing several organic dysfunctions, such as diabetes, cirrhosis, endocrinopathies and heart disease. Researchers have reported an association of iron overload with beta-thalassemia. The aim of this paper was to compare the serum ferritin levels of women with the beta-thalassemia trait. The results of serologic tests of 137 women of childbearing age were analyzed; 63 had the beta-thalassemia trait and 74 had Hb AA. In the beta-thalassemia carriers, the median ferritin value was 51.90 ng/mL and in the non-carriers 31.60 ng/mL (p = 0.0052. Levels of less than 20 and above 150 ng/mL were observed in 28% and 3% of the non-carriers and in 16% and 11% of the carriers, respectively. With these results it is possible to conclude that women in the reproductive age with the beta-thalassemia trait present higher ferritin levels in the northeastern region of São Paulo State. Further studies are necessary to clarify possible genetic and/or environment factors which interfere in iron absorption.

  15. Ab initio alpha-alpha scattering

    CERN Document Server

    Elhatisari, Serdar; Rupak, Gautam; Epelbaum, Evgeny; Krebs, Hermann; Lähde, Timo A; Luu, Thomas; Meißner, Ulf-G

    2015-01-01

    Processes involving alpha particles and alpha-like nuclei comprise a major part of stellar nucleosynthesis and hypothesized mechanisms for thermonuclear supernovae. In an effort towards understanding alpha processes from first principles, we describe in this letter the first ab initio calculation of alpha-alpha scattering. We use lattice effective field theory to describe the low-energy interactions of nucleons and apply a technique called the adiabatic projection method to reduce the eight-body system to an effective two-cluster system. We find good agreement between lattice results and experimental phase shifts for S-wave and D-wave scattering. The computational scaling with particle number suggests that alpha processes involving heavier nuclei are also within reach in the near future.

  16. The pharmaceutical vial capping process: Container closure systems, capping equipment, regulatory framework, and seal quality tests.

    Science.gov (United States)

    Mathaes, Roman; Mahler, Hanns-Christian; Buettiker, Jean-Pierre; Roehl, Holger; Lam, Philippe; Brown, Helen; Luemkemann, Joerg; Adler, Michael; Huwyler, Joerg; Streubel, Alexander; Mohl, Silke

    2016-02-01

    Parenteral drug products are protected by appropriate primary packaging to protect against environmental factors, including potential microbial contamination during shelf life duration. The most commonly used CCS configuration for parenteral drug products is the glass vial, sealed with a rubber stopper and an aluminum crimp cap. In combination with an adequately designed and controlled aseptic fill/finish processes, a well-designed and characterized capping process is indispensable to ensure product quality and integrity and to minimize rejections during the manufacturing process. In this review, the health authority requirements and expectations related to container closure system quality and container closure integrity are summarized. The pharmaceutical vial, the rubber stopper, and the crimp cap are described. Different capping techniques are critically compared: The most common capping equipment with a rotating capping plate produces the lowest amount of particle. The strength and challenges of methods to control the capping process are discussed. The residual seal force method can characterize the capping process independent of the used capping equipment or CCS. We analyze the root causes of several cosmetic defects associated with the vial capping process.

  17. Total alpha-globin gene cluster deletion has high frequency in Filipinos

    Energy Technology Data Exchange (ETDEWEB)

    Hunt, J.A.; Haruyama, A.Z.; Chu, B.M. [Kapiolani Medical Center, Honolulu, HI (United States)] [and others

    1994-09-01

    Most {alpha}-thalassemias [Thal] are due to large deletions. In Southeast Asians, the (--{sup SEA}) double {alpha}-globin gene deletion is common, 3 (--{sup Tot}) total {alpha}-globin cluster deletions are known: Filipino (--{sup Fil}), Thai (--{sup Thai}), and Chinese (--{sup Chin}). In a Hawaii Thal project, provisional diagnosis of {alpha}-Thal-1 heterozygotes was based on microcytosis, normal isoelectric focusing, and no iron deficiency. One in 10 unselected Filipinos was an {alpha}-Thal-1 heterozygote, 2/3 of these had a (--{sup Tot}) deletion: a {var_sigma}-cDNA probe consistently showed fainter intensity of the constant 5.5 kb {var_sigma}{sub 2} BamHI band, with no heterzygosity for {var_sigma}-globin region polymorphisms; {alpha}-cDNA or {var_sigma}-cDNA probes showed no BamHI or BglII bands diagnostic of the (--{sup SEA}) deletion; bands for the (-{alpha}) {alpha}-Thal-2 single {alpha}-globin deletions were only seen in Hb H cases. A reliable monoclonal anti-{var_sigma}-peptide antibody test for the (--{sup SEA}) deletion was always negative in (--{sup Tot}) samples. Southern digests with the Lo probe, a gift from D. Higgs of Oxford Univ., confirmed that 49 of 50 (--{sup Tot}) chromosomes in Filipinos were (--{sup Fil}). Of 20 {alpha}-Thal-1 hydrops born to Filipinos, 11 were (--{sup Fil}/--{sup SEA}) compound heterozygotes; 9 were (--{sup SEA}/--{sup SEA}) homozygotes, but none was a (--{sup Fil}/--{sup Fil}).

  18. Capping stack: An industry in the making

    Institute of Scientific and Technical Information of China (English)

    Jack Chen; Li Xunke; Xie Wenhui; Kang Yongtian

    2013-01-01

    This paper gives an overview of recent development of the marine well containment system (MWCS)after BP Macondo subsea well blowout occurred on April 20,2010 in the Gulf of Mexico.Capping stack,a hardware utilized to contain blowout well at or near the wellhead is the center piece of MWCS.Accessibility to the dedicated capping stacks is gradually becoming a pre-requirement to obtain the permit for offshore drilling/workover,and the industry for manufacturing,maintenance,transportation and operation of the capping stack is in the making.

  19. Disc-Capped ZnO Nanocombs

    Institute of Scientific and Technical Information of China (English)

    LI Xin; XU chun-xiang; ZHU Guang-Ping; YANG Yi; LIU Jin-Ping; SUN Xiao-Wei; CUI Yi-Ping

    2007-01-01

    Nanocombs with a disc cap structure of ZnO have been synthesized on si substrates by using pure Zinc powders as the source materials based on a vapour-phase transport process.The morphology and the microstructure are investigated by a scanning electron microscopy and x-ray diffraction.Based on the transmission electron microscopy and selected area electron diffraction analysis,the growth directions of three representative parts,nanoribbon stem,nanorod branch and nanodisc cap of the nanocomb are revealed.The growth mechanism of the disc-capped nanocombs is discussed based on the self-catalyzed vapour-liquid-solid process.

  20. Analysis of thalassemia gene of 269 couples%某地区269对夫妇珠蛋白生成障碍性贫血基因检测结果

    Institute of Scientific and Technical Information of China (English)

    张艳霞; 韩泽平

    2014-01-01

    Objective The pregnant population in Guangzhou area were detected in mediterranean anemia gene to guide and standardize the premarital examination ,prenatal diagnosis ,genetic counseling ,high-risk prenatal diagno-sis and prevent the birth of children with severe thalassemia .Methods 269 couples during the period from 2013 March to September ,for examination before pregnancy and blood MCV (mean corpuscular volume) and/or hemoglo-bin electrophoresis screening positive(538 cases) were detected in mediterranean anemia gene by agarose gel electro-phoresis and gap-PCR methods .Results 269 couples accepted detection ,detection of alpha thalassemia was 28 .4% , detection of beta thalassemia rate was 19 .5% ,among them ,the couple for alpha thalassemiawith detection rate was 5 .9% ,the same as the betathalassemia detection rate was 2 .2% ,one for the alpha thalassemia ,the other party or party for beta thalassemiaalpha beta composite to poverty ,the other normaldetection rate was 4 .5% .Conclusion Mediterranean anemia examination of reproductive population ,has an important significance to eugenics and reduce the social andeconomic burden of the family .%目的:对广州地区孕前人群进行珠蛋白生成障碍性贫血基因检测,以指导规范的婚前检查、产前检查,预防重症珠蛋白生成障碍性贫血患儿的出生。方法采用琼脂糖凝胶电泳及gap-PCR方法对2013年3~9月来院进行孕前检查并且血常规平均红细胞体积(MCV)和(或)血红蛋白电泳初筛阳性的269对夫妇(共538例)进行珠蛋白生成障碍性贫血基因检测。结果接受检测的269对夫妇中,α-珠蛋白生成障碍性贫血的检出率为28.4%,β-珠蛋白生成障碍性贫血的检出率为19.5%,其中,双方夫妇同为α-珠蛋白生成障碍性贫血的检出率为5.9%,同为β-珠蛋白生成障碍性贫血的检出率为2.2%,一方为α-珠蛋白生成障碍性贫血,另一方为β-珠蛋白

  1. Tumor necrosis factor induces phosphorylation of a 28-kDa mRNA cap-binding protein in human cervical carcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Marino, M.W.; Guidon, P.T. Jr.; Donner, D.B. (Cornell Univ. Graduate School of Medical Sciences, New York, NY (USA)); Pfeffer, L.M. (Rockefeller Univ., New York, NY (USA))

    1989-11-01

    Tumor necrosis factor {alpha} (TNF-{alpha}) stimulated the phosphorylation of a 28-kDa protein (p28) in the ME-180 line of human cervical carcinoma cells. The effect of TNF-{alpha} on the phosphorylation state of p28 was rapid (4-fold increase within 15 min) and persistent, remaining above the basal level for at least 2 hr. The specific binding of {sup 125}I-labeled TNF-{alpha} to cell-surface binding sites, the stimulation of p28 phosphorylation by TNF-{alpha}, and the inhibition of cell proliferation by TNF-{alpha} occurred with nearly identical dose-response relationships. Two-dimensional SDS/PAGE resolved p28 into two isoforms having pI values of 6.2 and 6.1. A phosphorylated cap-binding protein was substantially enriched from lysates of control or TNF-{alpha}-treated ME-180 cells by affinity chromatography with 7-methylguanosine 5{prime}-triposphate-Sepharose. The phosphoprotein recovered from this procedure was the substrate for TNF-{alpha}-promoted phosphorylation, p28. Thus, TNF-{alpha} stimulates the phosphorylation of this mRNA cap-binding protein, which may be involved in the transduction of TNF-{alpha}-receptor binding into cellular responses.

  2. Tumor necrosis factor induces phosphorylation of a 28-kDa mRNA cap-binding protein in human cervical carcinoma cells.

    Science.gov (United States)

    Marino, M W; Pfeffer, L M; Guidon, P T; Donner, D B

    1989-11-01

    Tumor necrosis factor alpha (TNF-alpha) stimulated the phosphorylation of a 28-kDa protein (p28) in the ME-180 line of human cervical carcinoma cells. The effect of TNF-alpha on the phosphorylation state of p28 was rapid (4-fold increase within 15 min) and persistent, remaining above the basal level for at least 2 hr. The specific binding of 125I-labeled TNF-alpha to cell-surface binding sites, the stimulation of p28 phosphorylation by TNF-alpha, and the inhibition of cell proliferation by TNF-alpha occurred with nearly identical dose-response relationships. Two-dimensional SDS/PAGE resolved p28 into two isoforms having pI values of 6.2 and 6.1. A phosphorylated cap-binding protein was substantially enriched from lysates of control or TNF-alpha-treated ME-180 cells by affinity chromatography with 7-methylguanosine 5'-triphosphate-Sepharose. The phosphoprotein recovered from this procedure was the substrate for TNF-alpha-promoted phosphorylation, p28. Thus, TNF-alpha stimulates the phosphorylation of this mRNA cap-binding protein, which may be involved in the transduction of TNF-alpha-receptor binding into cellular responses.

  3. The effects of beta-carotene and vitamin E on erythrocytes lipid peroxidation in beta-thalassemia patients

    Directory of Open Access Journals (Sweden)

    Soleiman Mahjoub

    2007-12-01

    Full Text Available BACKGROUND: Thalassemia is the most common hereditary disease in the world. Thalassemic erythrocytes are exposed to higher oxidative stress and lipid peroxidation. The aim of this study was to investigate the effects of beta-carotene and vitamin E on erythrocytes lipid peroxidation in beta-thalassemia patients.
    METHODS: A prospective double-blind, placebo-controlled study of the effect of beta-carotene and vitamin E on lipid peroxidation in erythrocytes membranes was performed on 120 beta-thalassemia major patients in four groups. The patients were supplemented for 4 weeks as follows: group 1 with beta-carotene (13 mg/day, group 2 with vitamin E (550 mg/day, group 3 with beta-carotene plus vitamin E and group 4 with placebo. We prepared all capsules for 4 roups in the same shape and color. Measurements of serum beta-carotene and vitamin E were performed by high performance
    liquid chromatography. After preparation of ghost cells from blood specimens, malondialdehyde (MDA was determined as index of lipid peroxidation in erythrocytes membranes before and after treatment. RESULTS: The levels of serum beta-carotene and vitamin E were significantly lower and MDA concentrations in erythrocytes membranes were significantly higher in beta-thalassemia patients compared to controls (P<0.001. In groups that treated with vitamin supplements for 4-weeks, lipid peroxidation rates were significantly reduced after treatment (P<0.001, but in placebo group there was not significant difference (P>0.05.
    CONCLUSIONS: Our findings provide evidence that an oral treatment with beta-carotene and vitamin E can significantly reduce lipid peroxidation of erythrocytes membranes and could be useful in management of beta-thalassemia major patients. KEYWORDS: Beta-thalassemia major, beta-carotene, vitamin E, malondialdehyde, lipid peroxidation.

  4. The Prevalence of Impaired Glucose Tolerance in Patients with Thalassemia Major in Iran: A systematic Review and Meta-analysis

    Directory of Open Access Journals (Sweden)

    M Azami

    2016-01-01

    Full Text Available Introduction: Impaired glucose tolerance (IGT is one of the most common endocrine complications in major thalassemia patients. IGT prevalence in patients with thalassemia major has been differently in different studies in Iran, about which no total estimate can be proposed. Hence, this meta analysis study aimed to investigate IGT prevalence in major thalassemia patients in Iran. Methods: This study was a systematic review based on electronic databases including Magiran, Iranmedex, SID, Medlib, IranDoc, Scopus, PubMed, Sciencedirect, Cochrane, Embase, Web of Science, Springer, Online Library Wiley as well as Google Scholar search engine without any time limitations up to 2015. All the potentially relevant papers were reviewed independently by two investigators using the standard key words. Then, all the reviewed studies that had inclusion criterion were evaluated. In order to statistically analyze the study data, random effect model was used via Stata software (Ver.11.1. Results: 1346 subjects were examined in 13 studies. IGT prevalence in patients with thalassemia major was estimated 9.6 %( CI: 95%, 6.6-12.5 in Iran. The IGT prevalence in male and female major thalassemia patients were 6.5 %( CI: 95%, 1.6-11.3 and 10.2 %( CI: 95% , 6.1-14.3, respectively. Conclusion: IGT Prevalence was demonstrated to be really high in patients with thalassemia major. As a result, implementing screening programs seems to be necessary in regard with early diagnosis of endocrine disorders especially IGT in these patients. Furthermore, it is recommended that annual glucose tolerance test be taken within such patients.

  5. Effectiveness of Eye Movement Desensitization and Reprocessing on Anxiety in Children with Thalassemia in a 12-month follow up

    Directory of Open Access Journals (Sweden)

    A Shahnavazi

    2016-02-01

    Full Text Available Background and  Objective: Thalassemia is the most common genetic diseases in the world and especially in our country. For many reasons, including chronic disease, health care costs, the expected mortality Ray disease states such as anxiety, psychological and social problems in thalassemia. The aim of the present study was to assess the efficacy of Eye Movement Desensitization and Reprocessing (EMDR on anxiety of children with thalassemia in a 12-month follow up..  Methods: It was a clinical trial study, which was performed on 60 patients with Thalassemia in 2013-2014. A total of 60 thalassemic patients based on Beck anxiety inventory, selected using sampling and were randomly divided into experimental and Control groups. in experimental group, eye movement desensitization and reprocessing therapy was perfomed in five sessions and The control group received no intervention. In order to collect information on demographic questionnaire and Beck Anxiety Inventory were used. data were gathered on anxiety symptoms at pretreatment, posttreatment and 12 month follow up and were analyzed using descriptive statistics, repeated measures and chi square. Results: The average age of the participants was 15.22±1.93  years old. This study shows that the mean or average level of anxiety children with thalassemia in the experimental group before and after intervention and in a 12-month follow up group 34.73 ± 5.62, 19.90 ± 2.48 and 19.23 ± 2.48 respectively; repeated measures ANOVA showed significant statistical difference (p.05 Conclusion: This study shows that Method of eye movement desensitization and reprocessing as an alternative method to treat or reduce anxiety, aggressive children with thalassemia .Trained Nurses can use this new method is effective in the treatment of anxiety.

  6. Inherited hemolytic disorders with high occurrence of b-thalassemia in Sindhi community of Jabalpur town in Madhya Pradesh, India

    Directory of Open Access Journals (Sweden)

    RS Balgir

    2010-04-01

    Full Text Available Hereditary hemolytic disorders such as hemoglobin disorders, β-thalassemia syndrome, G6PD deficiency, and ABO and Rhesus blood groups are the most common public health problems in India. Community genetic screening provides multifaceted information for finding prevalence, level of health education, preventive strategies such as genetic/marriage counseling to relieve the burden of vulnerable communities. However, such genetic screening studies are scanty in India. This study aims to find the prevalence of inherited hemolytic disorders in Sindhi community, identify the persons for genetic/marriage counseling and to suggest the relevant strategies for prevention and control to the affected families. A cross-sectional random study of 508 persons of Sindhi community belonging to all ages and both sexes was conducted for screening of hemoglobin disorders, G6PD deficiency and ABO and Rhesus (D blood groups following the standard procedures and techniques from Jabalpur town in Central India. High frequency of β-thalassemia trait (20.5%, Hb D trait (2.2% and hemoglobin D/β-thalassemia (0.2%, G6PD deficiency (0.8%, and a low prevalence of Rhesus negative (3.0% blood group was observed in Sindhi community of Jabalpur town in Madhya Pradesh. A case of β-thalassemia major and Hb D-thalassemia were also encountered. Double heterozygosity of Hb D/β-thalassemia showed hypochromic and microcytic red cell morphology with mild anemia. Inherited hemolytic disorders are an important public health challenge in Sindhi community. Preventive genetics program needs to be vigorously taken up to ameliorate the sufferings of at risk communities in India.

  7. 广西百色市胎儿羊水地中海贫血基因检测分析%Detection and analysis of thalassemia gene of the fetal amniotic fluid in baise city

    Institute of Scientific and Technical Information of China (English)

    罗宏成; 王春芳; 向阳; 雷茗; 邓鹰; 韦叶生

    2015-01-01

    目的:运用分子杂交和基因芯片技术对百色市地中海贫血(简称“地贫”)孕妇进行羊水地贫基因检测,了解地贫胎儿的发病率及基因突变类型.方法:采用跨跃断裂点聚合酶链反应(gap-PCR)及膜-反向点杂交技术检测中国人常见的缺失型α-地中海贫血、突变型α-地中海贫血及β-地中海贫血.结果:检出单纯性α-地中海贫血145例(47.3%),中、重型α-地中海贫血52(36.2%),重型 Bart's 水肿胎儿16例(11.3%),中型血红蛋白 H 病(HbH)病36例(24.8%);单纯性β-地中海贫血103例(33.6%),β-地中海贫血中重型28例(27.2%);复合型αβ地中海贫血21例(6.8%);壮族人群α-地中海贫血发生率为56.6%,瑶族人群α-地中海贫血发生率为27.6%,汉族人群检出α-地中海贫血发生率为15.8%;壮族人群β-地中海贫血发生率为66.0%,瑶族人群β-地中海贫血发生率为21.4%,汉族人群β-地中海贫血发生率为12.6%.结论:百色地区胎儿羊水地贫基因检测阳性率较高,特别是中重型地中海贫血类型胎儿阳性率也很高;壮、瑶、汉各民族α-地中海贫血的发病率具有显著性差异(P <0.05),壮、瑶、汉各民族β-地中海贫血的发病率无统计学差异(P >0.05).对该地区孕育胎儿的夫妇应该进行产前地中海贫血基因筛查及孕育知识的长期指导.%Aim:Using the molecular hybridization and gene chip technology to detect the thalassemia gene of pregnant women with thalassemia in Baise city,to learn the incidence and mutation types of the Fetal with thalassemia.Methods:Using the gap Polymerase Chain Reaction(gap-PCR)and membrane-reverse dot hybridization technique to detect the lack of Chinese common type of alpha thalassaemia,the mutant of alpha thalassaemia and beta thalassaemia.Results:One hundred and forty-five cases were di-agnosed with

  8. Embryo genome profiling by single-cell sequencing for preimplantation genetic diagnosis in a β-thalassemia family

    DEFF Research Database (Denmark)

    Xu, Yanwen; Chen, Shengpei; Yin, Xuyang

    2015-01-01

    for a β-thalassemia-carrier couple to have a healthy second baby. We carried out sequencing for single blastomere cells and the family trio and further developed the analysis pipeline, including recovery of the missing alleles, removal of the majority of errors, and phasing of the embryonic genome...... leukocyte antigen matching tests. CONCLUSIONS: This retrospective study in a β-thalassemia family demonstrates a method for embryo genome recovery through single-cell sequencing, which permits detection of genetic variations in preimplantation genetic diagnosis. It shows the potential of single...

  9. α:Non–α and Gγ:Aγ globin chain ratios in thalassemia intermedia patients treated with hydroxyurea

    Directory of Open Access Journals (Sweden)

    Abbas Najjari

    2014-05-01

    Conclusions: Improvement in α:non-α ratio and consequent decrease of free α-globin chain might be the cause of beneficial effects of hydroxyurea therapy. Two patients who felt better didn't show significant increase in their fetal hemoglobin level, and this is in contradiction with the hypothesis claiming that the HbF level increase is the cause of such therapeutic effect. In spite of the unclear mechanism of action of this drug, hydroxyurea therapy had noticeable impacts on thalassemia intermedia and also sickle cell disease and even patients suffering from thalassemia major.

  10. Beta-thalassemia mutations in Rome. A high frequency of the IVSII-745 allele in subjects of latium origin.

    Science.gov (United States)

    Massa, A; Cianciulli, P; Cianetti, L; Iazzone, R; Cenci, A; Sorrentino, F; Franco, G; Pecci, G; Papa, G; Peschle, C

    1994-01-01

    We studied the molecular bases of beta-thalassemia in Rome, a city centrally located in Latium, which is a region with a low incidence of beta-carriers. People also come to Rome from other regions for specific or prenatal diagnostic assessment. Only 11 patients (20%) out of 62 characterized beta-thalassemia subjects were of Latium family origin. They presented five mutations with an uncommonly high frequency of the IVSII-745 allele, that was found in homozygosis in 4 unrelated patients from a southeastern area in the province of Frosinone. These data may indicate a founder effect.

  11. The analysis on morbidity and genotypes distribution of thalassemia in married couples of child - bearing age in Dongyuan county of Guangdong province%广东省东源县已婚育龄夫妇地中海贫血发病率及基因型分布现况分析

    Institute of Scientific and Technical Information of China (English)

    杨心琼; 黄桥海; 黄碧兰; 洪玉珍; 徐嘉; 刘晃; 王瑾; 赵文忠; 韦相才

    2014-01-01

    Objective Screening thalassemia in married couples of child-bearing age in Dongyuan county of Guangdong province through the national pre -pregnancy eugenics inspection technology platform. To analyze the situation of morbidity and genotypes distribution of thalassemia in married couples of child-bearing age, to provide references for prevention of thalassemia. Methods The thalassemia screening were conducted in married couples of child-bearing age during the 2011 to 2013 in Dongyuan county. Data of mean corpuscular volume ( MCV) , mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC),et al were collected. The positive patients were identified for the genotype of thalassemia. Patients with positive gene mutations were given genetic counseling and reproductive guidance. Results 14 334 cases were conducted the screening, of which 1 662 cases were considered as thalassemia in the preliminary screening with the morbidity of 11. 59%, 916 male patients with MCHC of (258. 08 ± 21. 02)g/L, MCV of (69. 19 ± 6. 44)fl, MCH of(19. 16 ± 4. 70)pg and 746 female patients with MCHC of ( 255. 46 ± 34. 62 ) g/L, MCV of ( 69. 79 ± 4. 33 ) fl, MCH of ( 19. 73 ± 4. 27 ) pg, no significant difference in morbidity of thalassemia were found between the two groups (P>0. 05). 1 163cases were confirmed by gene diagnosis, of which 674 cases(57. 95%) got the alpha thalassemia and 378 cases(32. 50%) got the β thalassemia. Conclusion Morbidity of thalassemia is quite high in Dongyuan county of Guangdong province, and the characteristics ofαthalassemin genothpe andβ-thalassemia genotype were consistent with that in Guangdong province. It is important for improving quality of newborn population though thalassemia screening and genetic diagnosis in child-bearing age population.%目的:利用国家孕前优生检查技术平台,对广东省东源县已婚育龄夫妇进行地中海贫血(简称地贫)筛查,了解其发病率及基因型分布情况,为地

  12. C-CAP Land Cover, Kauai, Hawaii

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set consists of land derived from high resolution imagery and was analyzed according to the Coastal Change Analysis Program (C-CAP) protocol to determine...

  13. C-CAP Land Cover, Maui, Hawaii

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set consists of land derived from high resolution imagery and was analyzed according to the Coastal Change Analysis Program (C-CAP) protocol to determine...

  14. C-CAP Land Cover, Molokai, Hawaii

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set consists of land derived from high resolution imagery and was analyzed according to the Coastal Change Analysis Program (C-CAP) protocol to determine...

  15. C-CAP Land Cover, Lanai, Hawaii

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set consists of land derived from high resolution imagery and was analyzed according to the Coastal Change Analysis Program (C-CAP) protocol to determine...

  16. Circumpolar Active-Layer Permafrost System (CAPS)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Circumpolar Active-Layer Permafrost System (CAPS) contains over 100 data sets pertaining to permafrost and frozen ground topics. It also contains detailed...

  17. C-CAP Hawaii 2005 Land Cover

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set consists of land derived from high resolution imagery and was analyzed according to the Coastal Change Analysis Program (C-CAP) protocol to determine...

  18. Cryopyrin-Associated Autoinflammatory Syndromes (CAPS) - Juvenile

    Science.gov (United States)

    ... of the nervous system, including headaches and deafness. CAPS are not contagious. Treatments that block interleukin-1, an important molecule involved in the inflammatory process, are very effective. To prevent permanent damage, treatment ...

  19. C-CAP Land Cover, Niihau, Hawaii

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set consists of land derived from high resolution imagery and was analyzed according to the Coastal Change Analysis Program (C-CAP) protocol to determine...

  20. C-CAP Niihau 2005 Land Cover

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set consists of land cover derived from high resolution imagery according to the Coastal Change Analysis Program (C-CAP) protocol. This data set utilized 1...

  1. Molecular Basis and prenatal diagnosis of B- Thalassemia in Southeast if Iran

    Directory of Open Access Journals (Sweden)

    E. Miri Moghadam

    2005-01-01

    Full Text Available Background and purpose : bata thlassemia is the most common monogenic disorders in Iran. The gene frequency varies the country. Sistan and Baluchistan province, located in the southeast of iran with more than 1200 affected individuals, represents one of the regions where thalassemia id not only an important public health problem but also a socioeconomic problem. As a matter of fact high frequency of ß- thalassemia gene inter- family marriages, evasion of couples to carry out pre- marriage blood test, avoidance of counseling before wedding and eagerness for more children in spite of having ß - thalassemia kids collectively prompted us to eatablish prenatal diagnostic center in khordad 1381(May 2002 in this province.Materials and methods : 140 minor thalassemia couples were referred to our center from May 2002 to Feb. 2004. After admission of the couples to the center their demographic data were collected. 10 ml of blood sample was then collected from couples added with anti- coaqulant(0.5 M EDTA. DNA was subsequently extracted before being amplified by Refractory Mutation System(ARMS techniques vs the common primers of B- gene mutations in Iran. Within the 10 to 12th weeks of pregnancy, chorionic villi samples were taken and subjected onto two techniques namely direct and indirect. We afterwards evaluated the inheritance of mutation in the fetus from any of his/ her parents.Results : We carried out preliminary diagnosis for 56 couples, as well as first round and further step of prenatal diagnostic procedures for another 84 couples(n= 140. 79. 3% of the total number resided in cities, whereas 87.9% were born in Sistan and Baluchistan province. Out of which 30% and 70% had sistany and Baluchi ethnicity respectively. Furthermore, 60.7% had at least one affected child, while 85.7% had consanguineous marriages. Out of the totalnumber, 57.9% were from Sunni minority. 88.05% of the couples demonstrated one of the common mutations identified in Iran

  2. Righting an ATLAS end-cap

    CERN Multimedia

    Maximilien Brice

    2003-01-01

    Each component of the giant ATLAS detector must be moved and transported with great caution so that delicate components are not damaged. Therefore, tests are performed, like the one shown. The end-cap weighs 160 tonnes, making the delicate moving process a non-trivial feat. A special crane and supports have been designed so that the end-cap can be raised using a pivot.

  3. Design and implementation of the CAPS receiver

    Science.gov (United States)

    Hu, Yonghui; Hua, Yu; Hou, Lei; Wei, Jingfa; Wu, Jianfeng

    2009-03-01

    In this paper, based on analyses of the Chinese Area Positioning System (CAPS) satellite (GEO satellite) resources and signal properties, the signal power at the port of the receiver antenna is estimated, and the implementation projects are presented for a switching band C to band L CAPS C/A code receiver integrated with GPS receiver suite and for a CAPS dual frequency P code receiver. A microstrip receiving antenna is designed with high sensitivity and wide beam orientation, the RF front end of the C/A code and P code receivers, and a processor is designed for the navigation baseband. A single frequency CAPS C/A code receiver and a CAPS dual frequency P code receiver are built at the same time. A software process flow is provided, and research on relatively key techniques is also conducted, such as signal searching, code loop and carrier loop algorithms, a height assistant algorithm, a dual frequency difference speed measurement technique, a speed measurement technique using a single frequency source with frequency assistance, and a CAPS time correcting algorithm, according to the design frame of the receiver hardware. Research results show that the static plane positioning accuracy of the CAPS C/A code receiver is 20.5-24.6 m, height accuracy is 1.2-12.8 m, speed measurement accuracy is 0.13-0.3 m/s, dynamic plane positioning accuracy is 24.4 m, height accuracy is 3.0 m, and speed measurement accuracy is 0.24 m/s. In the case of C/A code, the timing accuracy is 200 ns, and it is also shown that the positioning accuracy of the CAPS precise code receiver (1 σ) is 5 m from south to north, and 0.8 m from east to west. Finally, research on positioning accuracy is also conducted.

  4. Design and implementation of the CAPS receiver

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    In this paper, based on analyses of the Chinese Area Positioning System (CAPS) satellite (GEO satellite) resources and signal properties, the signal power at the port of the receiver antenna is estimated, and the implementation projects are presented for a switching band C to band L CAPS C/A code receiver integrated with GPS receiver suite and for a CAPS dual frequency P code receiver. A microstrip receiving antenna is designed with high sensitivity and wide beam orientation, the RF front end of the C/A code and P code receivers, and a processor is designed for the navigation baseband. A single frequency CAPS C/A code receiver and a CAPS dual frequency P code receiver are built at the same time. A software process flow is provided, and research on relatively key techniques is also conducted, such as signal searching, code loop and carrier loop algorithms, a height assistant algorithm, a dual frequency difference speed measurement technique, a speed measurement technique using a single frequency source with frequency assistance, and a CAPS time correcting algorithm, according to the design frame of the receiver hardware. Research results show that the static plane positioning accuracy of the CAPS C/A code receiver is 20.5-24.6 m, height accuracy is 1.2-12.8 m, speed measurement accuracy is 0.13-0.3 m/s, dynamic plane positioning accuracy is 24.4 m, height accuracy is 3.0 m, and speed measurement accuracy is 0.24 m/s. In the case of C/A code, the timing accuracy is 200 ns, and it is also shown that the positioning accuracy of the CAPS precise code receiver (1σ ) is 5 m from south to north, and 0.8 m from east to west. Finally, research on positioning accuracy is also conducted.

  5. Plasma lipid pattern and red cell membrane structure in β-thalassemia patients in Jakarta

    Directory of Open Access Journals (Sweden)

    Seruni K.U. Freisleben

    2011-08-01

    Full Text Available Background: Over the last 10 years, we have investigated thalassemia patients in Jakarta to obtain a comprehensive picture of iron overload, oxidative stress, and cell damage.Methods: In blood samples from 15 transfusion-dependent patients (group T, 5 non-transfused patients (group N and 10 controls (group C, plasma lipids and lipoproteins, lipid-soluble vitamin E, malondialdehyde (MDA and thiol status were measured. Isolated eryhtrocyte membranes were investigated with electron paramagnetic resonance (EPR spectroscopy using doxyl-stearic acid and maleimido-proxyl spin lables. Data were analyzed statistically with ANOVA.Results: Plasma triglycerides were higher and cholesterol levels were lower in thalassemic patients compared to controls. Vitamin E, group C: 21.8 vs T: 6.2 μmol/L and reactive thiols (C: 144 vs. T: 61 μmol/L were considerably lower in transfused patients, who exert clear signs of oxidative stress (MDA, C: 1.96 vs T: 9.2 μmol/L and of tissue cell damage, i.e., high transaminases plasma levels. Non-transfused thalassemia patients have slight signs of oxidative stress, but no significant indication of cell damage. Erythrocyte membrane parameters from EPR spectroscopy differ considerably between all groups. In transfusion-dependent patients the structure of the erythrocyte membrane and the gradients of polarity and fluidity are destroyed in lipid domains; binding capacity of protein thiols in the membrane is lower and immobilized.Conclusion: In tranfusion-dependent thalassemic patients, plasma lipid pattern and oxidative stress are associated with structural damage of isolated erythrocyte membranes as measured by EPR spectroscopy with lipid and proteinthiol spin labels. (Med J Indones 2011; 20:178-84Keywords: electron paramagnetic resonance spectroscopy, erythrocyte membrane, lipoproteins, oxidative stress, thalassemia, plasma lipids.

  6. Clinical and Molecular Characteristics of Non-Transfusion-Dependent Thalassemia in Kuwait.

    Science.gov (United States)

    Adekile, Adekunle D; Azab, Asma F; Al-Sharida, Sondus I; Al-Nafisi, Bahia A; Akbulut, Nagihan; Marouf, Rajaa A; Mustafa, Nada Y

    2015-01-01

    Although not regularly transfused, patients with non-transfusion-dependent thalassemia (NTDT) are prone to iron overload and its complications. Their molecular, phenotypical and laboratory characteristics vary in different populations and there is a need to document local prevailing patterns. We have reviewed the records of our patients with NTDT in Kuwait and documented their clinical and molecular characteristics in addition to iron status [serum ferritin and liver magnetic resonance imaging (MRI) T2*], management and complications. There were 41 patients, made up of 20 with β-thalassemia intermedia (β-TI), 18 with Hb H (β4) disease and three with Hb E (HBB: c.79G > A)-β-thalassemia (Hb E-β-thal); their ages ranged from 3 to 36 years (mean 12.5 ± 7.7). While 18 (43.9%) had been transfused at least once, only three (7.3%) had been transfused on multiple occasions. Three patients had serum ferritin >500 ng/mL; while four of 38 had mild or moderate liver iron overload. Seven (35.0%) of the β-TI patients were managed with hydroxyurea (HU) with good response. Other complications included five patients with gallstones and one each of hypothyroidism and moyamoya. The most common mutations among the β-TI patients were IVS-II-1 (G > A) and IVS-I-6 (T > C), while among the Hb H patients, the Saudi α2-globin gene polyadenylation (polyA) (AATAAA > AATAAG) mutation was responsible for all cases either as homozygotes (61.1%) or compound heterozygotes with the α-thal-2 (-α(3.7)) allele (33.3%). Although the pattern of NTDT in Kuwaiti patients is generally mild, there is a need to follow them to adulthood as the complications are cumulative and more prevalent in this group.

  7. Side effects of Deferasirox Iron Chelation in Patients with Beta Thalassemia Major or Intermedia

    Directory of Open Access Journals (Sweden)

    Murtadha Al-Khabori

    2013-03-01

    Full Text Available Objectives: Chelating agents remain the mainstay in reducing the iron burden and extending patient survival in homozygous beta-thalassemia but adverse and toxic effects may increase with the institution and long term use of this essential therapy. This study aimed to estimate the incidence of deferasirox (DFX side effects in patients with thalassemia major or intermedia.Methods: A retrospective study of 72 patients (mean age: 20.3±0.9 yrs; 36 male, 36 female with thalassemia major or intermedia treated at Sultan Qaboos University Hospital, Oman, was performed to assess the incidence of side effects related to deferasirox over a mean of 16.7 month follow-up period.Results: Six patients experienced rashes and 6 had gastro-intestinal upset. DFX was discontinued in 18 patients for the following reasons: persistent progressive rise(s in serum creatinine (7 patients; 40% mean serum creatinine rise from baseline, feeling unwell (2, severe diarrhea (1, pregnancy (1, death unrelated to chelator (2 and rise in serum transaminases (2. Three patients were reverted to desferoxamine and deferiprone combination therapy as DFX was no longer biochemically effective after 18 months of therapy. There was no correlation between baseline serum ferritin and serum creatinine or a rise in serum creatinine. Cardiac MRI T2* did not change with DFX therapy. However, there was an improvement in liver MRI T2* (p=0.013.Conclusion: Renal side effects related to deferasirox appear to be higher than those reported in published clinical trials. Further larger studies are required to confirm these findings.

  8. Side effects of Deferasirox Iron Chelation in Patients with Beta Thalassemia Major or Intermedia

    Science.gov (United States)

    Al-Khabori, Murtadha; Bhandari, Sunil; Al-Huneini, Mohammed; Al-Farsi, Khalil; Panjwani, Vinodh; Daar, Shahina

    2013-01-01

    Objectives Chelating agents remain the mainstay in reducing the iron burden and extending patient survival in homozygous beta-thalassemia but adverse and toxic effects may increase with the institution and long term use of this essential therapy. This study aimed to estimate the incidence of deferasirox (DFX) side effects in patients with thalassemia major or intermedia. Methods A retrospective study of 72 patients (mean age: 20.3±0.9 yrs; 36 male, 36 female) with thalassemia major or intermedia treated at Sultan Qaboos University Hospital, Oman, was performed to assess the incidence of side effects related to deferasirox over a mean of 16.7 month follow-up period. Results Six patients experienced rashes and 6 had gastro-intestinal upset. DFX was discontinued in 18 patients for the following reasons: persistent progressive rise(s) in serum creatinine (7 patients; 40% mean serum creatinine rise from baseline), feeling unwell (2), severe diarrhea (1), pregnancy (1), death unrelated to chelator (2) and rise in serum transaminases (2). Three patients were reverted to desferoxamine and deferiprone combination therapy as DFX was no longer biochemically effective after 18 months of therapy. There was no correlation between baseline serum ferritin and serum creatinine or a rise in serum creatinine. Cardiac MRI T2* did not change with DFX therapy. However, there was an improvement in liver MRI T2* (p=0.013). Conclusion Renal side effects related to deferasirox appear to be higher than those reported in published clinical trials. Further larger studies are required to confirm these findings. PMID:23599881

  9. Low prevalence of fibrosis in thalassemia major assessed by late gadolinium enhancement cardiovascular magnetic resonance

    Directory of Open Access Journals (Sweden)

    Tanner Mark A

    2011-01-01

    Full Text Available Abstract Background Heart failure remains a major cause of mortality in thalassaemia major. The possible role of cardiac fibrosis in thalassemia major in the genesis of heart failure is not clear. It is also unclear whether cardiac fibrosis might arise as a result of heart failure. Methods We studied 45 patients with thalassaemia major who had a wide range of current cardiac iron loading and included patients with prior and current heart failure. Myocardial iron was measured using T2* cardiovascular magnetic resonance (CMR, and following this, late gadolinium enhancement (LGE was used to determine the presence of macroscopic myocardial fibrosis. Results The median myocardial T2* in all patients was 22.6 ms (range 5.3-58.8 ms. Fibrosis was detected in only one patient, whose myocardial T2* was 20.1 ms and left ventricular ejection fraction 57%. No fibrosis was identified in 5 patients with a history of heart failure with full recovery, in 3 patients with current left ventricular dysfunction undergoing treatment, or in 18 patients with myocardial iron loading with cardiacT2* Conclusion This study shows that macroscopic myocardial fibrosis is uncommon in thalassemia major across a broad spectrum of myocardial iron loading. Importantly, there was no macroscopic fibrosis in patients with current or prior heart failure, or in patients with myocardial iron loading without heart failure. Therefore if myocardial fibrosis indeed contributes to myocardial dysfunction in thalassemia, our data combined with the knowledge that the myocardial dysfunction of iron overload can be reversed, indicates that any such fibrosis would need to be both microscopic and reversible.

  10. Mithramycin encapsulated in polymeric micelles by microfluidic technology as novel therapeutic protocol for beta-thalassemia

    Directory of Open Access Journals (Sweden)

    Capretto L

    2012-01-01

    Full Text Available Lorenzo Capretto1, Stefania Mazzitelli2, Eleonora Brognara2, Ilaria Lampronti2, Dario Carugo1, Martyn Hill1, Xunli Zhang1, Roberto Gambari2, Claudio Nastruzzi31Engineering Sciences, University of Southampton, Southampton, UK; 2Department of Biochemistry and Molecular Biology, 3Department of Pharmaceutical Sciences, University of Ferrara, Ferrara, ItalyAbstract: This report shows that the DNA-binding drug, mithramycin, can be efficiently encapsulated in polymeric micelles (PM-MTH, based on Pluronic® block copolymers, by a new microfluidic approach. The effect of different production parameters has been investigated for their effect on PM-MTH characteristics. The compared analysis of PM-MTH produced by microfluidic and conventional bulk mixing procedures revealed that microfluidics provides a useful platform for the production of PM-MTH with improved controllability, reproducibility, smaller size, and polydispersity. Finally, an investigation of the effects of PM-MTH, produced by microfluidic and conventional bulk mixing procedures, on the erythroid differentiation of both human erythroleukemia and human erythroid precursor cells is reported. It is demonstrated that PM-MTH exhibited a slightly lower toxicity and more pronounced differentiative activity when compared to the free drug. In addition, PM-MTH were able to upregulate preferentially γ-globin messenger ribonucleic acid production and to increase fetal hemoglobin (HbF accumulation, the percentage of HbF-containing cells, and their HbF content without stimulating α-globin gene expression, which is responsible for the clinical symptoms of ß-thalassemia. These results represent an important first step toward a potential clinical application, since an increase in HbF could alleviate the symptoms underlying ß-thalassemia and sickle cell anemia. In conclusion, this report suggests that PM-MTH produced by microfluidic approach warrants further evaluation as a potential therapeutic protocol

  11. Survey on relation between Major Thalassemia and Desferiexamine with renal tubular damage.

    Directory of Open Access Journals (Sweden)

    H.M. Jafari, M.D.

    2007-01-01

    Full Text Available AbstractBackground and Purpose: Thalassemia is a hereditary quantitative hemoglubinopathy which is common in mediteranian area including IRAN. Homos zygotic thalassemia patients suffer from severe anemia and complication of the disease in many organs. Studies have shown different results about renal complication and disease. Thus, in this study we investigated renal function of thalassemia Major (TM patients in comparison with control group.Materials and Methods: This was a historical cohort Study. The population who TM patients was were admitted to Boalisina hospital, Sari, and control group were brothers and sisters of the patients who were matched in gender and age. Serum and urine markers of renal function were measured and demographic and therapeutic data were gathered from medical records. Analysis of the data was performed using SPSS 11 with statistical test (t, chi square.Results: the Total of 84 (42 patients and, 42 controls patients were studied. The Mean age of the patients was years. Dose of Deferral was 70±19 mg/kg. The results showed no significant statistical differences in levels of microglobulin, 24 urine protein, Excretion Fraction of Na and K between case and control group. There was significant differences in levels of serum BUN, creatinin, Potassium and urine potassium and creatinin between case and control group. Gender, level of Hb and serum Ferritin significantly affected the differences between two groups.Conclusion: In this study, evidences of renal tubular damage were not detected in TM patients. There was increase in levels of Bun, serum potassium, uric Acid, specially with sever anemia, high dose desferal and Iron over load.

  12. The Correlation between Troponin and Ferritin Serum Levels in the Patients with Major Beta-Thalassemia

    Directory of Open Access Journals (Sweden)

    Iraj Shahramian

    2013-06-01

    Full Text Available Background: Thalassemia is a hereditary hemoglobinopathy whose most common complication is cardiac involvement which ends up in these patients’ death. Since troponin is a sensitive and specific marker for the detection of microinfarct, we studied the relationship between troponin and ferritin serum levels for early diagnosis of cardiac involvement in these patients. Materials and Methods: This case-control study was performed on 80 patients, including 40 patients with major thalassemia and normal echocardiography and 40 healthy volunteers ranging from 6 months to 16 years old. All the children were examined and the eligible children who were not infected with known heart disease, iron deficiency anemia, kidney disease, diabetes, fever, and systemic diseases were enrolled into the study after obtaining written informed consents from their parents. At 8:00 A.M. before breakfast, 5cc blood was drawn from these children. After collecting the samples, ferritin and troponin serum levels were evaluated using ELISA and electro- kymonolonsense methods, respectively. The gathered data were analyzed through the SPSS statistical software (v. 20 and T-test. Besides, P value<0.05 was considered as statistically significant. Results: The study results revealed a significant difference between the two groups regarding the mean of the serum levels of troponin (P=0.045 and ferritin (P=0.001. In this study, no significant correlation was observed between serum troponin and ferritin levels and age and BMI in the two groups. Also, no significant relationship was found between serum troponin level and sex (P=0.264. Conclusions: In microinfarct, troponin increases independent of ferritin; therefore, it can be used for early detection of cardiac involvement in thalassemia patients to determine the sub-clinical effects.

  13. Molecular Basis of β-Thalassemia Intermedia in Erbil Province of Iraqi Kurdistan.

    Science.gov (United States)

    Shamoon, Rawand P; Al-Allawi, Nasir A S; Cappellini, Maria D; Di Pierro, Elena; Brancaleoni, Valentina; Granata, Francesca

    2015-01-01

    β-Thalassemia intermedia (β-TI) is a clinical term describing a range of clinical phenotypes that are intermediate in severity between the carrier state and β-thalassemia major (β-TM). To characterize the molecular basis of β-TI in Erbil Province, Northern Iraq, 83 unrelated patients were investigated. Detection of β-globin gene mutations was carried out by reverse hybridization assay and direct gene sequencing. All patients were screened for the XmnI polymorphism by direct sequencing of HBG2 ((G)γ promoter gene). Detection of α-globin gene deletions and triplication was carried out using the reverse hybridization assay. Four main molecular patterns were identified in association with the β-TI phenotype, namely: β(+)/β(+) (38.5%), β(+)/β(0) (21.6%), β(0)/β(0) (31.3%), and β(0)/wild type (8.4%). IVS-I-6 (T > C) was the most frequently encountered mutation (55 alleles, 34.6%), followed by IVS-II-1 (G > A) and codon 8 (-AA); furthermore, we report for the first time from Iraq two β(+) mutations, -87 (C > G) and 5' untranslated region (5'UTR) +22 (G > A). The XmnI polymorphism was detected in 47.0% of patients, mainly in association with the β(0)/β(0) genotype. The α-globin gene deletions were encountered in four cases, including one case with (- -(FIL)) double gene deletion, a report that is the first from our country. The α-globin gene triplication was detected in five of the seven heterozygous β-thalassemia (β-thal) patients. Similar to other Mediterranean countries, inheritance of mild β-globin mutations was the main molecular pattern underlying β-TI in our patients followed by the ameliorating effect of the XmnI polymorphism.

  14. Therapeutic hemoglobin levels after gene transfer in β-thalassemia mice and in hematopoietic cells of β-thalassemia and sickle cells disease patients.

    Directory of Open Access Journals (Sweden)

    Laura Breda

    Full Text Available Preclinical and clinical studies demonstrate the feasibility of treating β-thalassemia and Sickle Cell Disease (SCD by lentiviral-mediated transfer of the human β-globin gene. However, previous studies have not addressed whether the ability of lentiviral vectors to increase hemoglobin synthesis might vary in different patients.We generated lentiviral vectors carrying the human β-globin gene with and without an ankyrin insulator and compared their ability to induce hemoglobin synthesis in vitro and in thalassemic mice. We found that insertion of an ankyrin insulator leads to higher, potentially therapeutic levels of human β-globin through a novel mechanism that links the rate of transcription of the transgenic β-globin mRNA during erythroid differentiation with polysomal binding and efficient translation, as reported here for the first time. We also established a preclinical assay to test the ability of this novel vector to synthesize adult hemoglobin in erythroid precursors and in CD34(+ cells isolated from patients affected by β-thalassemia and SCD. Among the thalassemic patients, we identified a subset of specimens in which hemoglobin production can be achieved using fewer copies of the vector integrated than in others. In SCD specimens the treatment with AnkT9W ameliorates erythropoiesis by increasing adult hemoglobin (Hb A and concurrently reducing the sickling tetramer (Hb S.Our results suggest two major findings. First, we discovered that for the purpose of expressing the β-globin gene the ankyrin element is particularly suitable. Second, our analysis of a large group of specimens from β-thalassemic and SCD patients indicates that clinical trials could benefit from a simple test to predict the relationship between the number of vector copies integrated and the total amount of hemoglobin produced in the erythroid cells of prospective patients. This approach would provide vital information to select the best candidates for these

  15. Therapeutic hemoglobin levels after gene transfer in β-thalassemia mice and in hematopoietic cells of β-thalassemia and sickle cells disease patients.

    Science.gov (United States)

    Breda, Laura; Casu, Carla; Gardenghi, Sara; Bianchi, Nicoletta; Cartegni, Luca; Narla, Mohandas; Yazdanbakhsh, Karina; Musso, Marco; Manwani, Deepa; Little, Jane; Gardner, Lawrence B; Kleinert, Dorothy A; Prus, Eugenia; Fibach, Eitan; Grady, Robert W; Giardina, Patricia J; Gambari, Roberto; Rivella, Stefano

    2012-01-01

    Preclinical and clinical studies demonstrate the feasibility of treating β-thalassemia and Sickle Cell Disease (SCD) by lentiviral-mediated transfer of the human β-globin gene. However, previous studies have not addressed whether the ability of lentiviral vectors to increase hemoglobin synthesis might vary in different patients.We generated lentiviral vectors carrying the human β-globin gene with and without an ankyrin insulator and compared their ability to induce hemoglobin synthesis in vitro and in thalassemic mice. We found that insertion of an ankyrin insulator leads to higher, potentially therapeutic levels of human β-globin through a novel mechanism that links the rate of transcription of the transgenic β-globin mRNA during erythroid differentiation with polysomal binding and efficient translation, as reported here for the first time. We also established a preclinical assay to test the ability of this novel vector to synthesize adult hemoglobin in erythroid precursors and in CD34(+) cells isolated from patients affected by β-thalassemia and SCD. Among the thalassemic patients, we identified a subset of specimens in which hemoglobin production can be achieved using fewer copies of the vector integrated than in others. In SCD specimens the treatment with AnkT9W ameliorates erythropoiesis by increasing adult hemoglobin (Hb A) and concurrently reducing the sickling tetramer (Hb S).Our results suggest two major findings. First, we discovered that for the purpose of expressing the β-globin gene the ankyrin element is particularly suitable. Second, our analysis of a large group of specimens from β-thalassemic and SCD patients indicates that clinical trials could benefit from a simple test to predict the relationship between the number of vector copies integrated and the total amount of hemoglobin produced in the erythroid cells of prospective patients. This approach would provide vital information to select the best candidates for these clinical trials

  16. Faddeev calculation of 3 alpha and alpha alpha Lambda systems using alpha alpha resonating-group method kernel

    CERN Document Server

    Fujiwara, Y; Kohno, M; Suzuki, Y; Baye, D; Sparenberg, J M

    2004-01-01

    We carry out Faddeev calculations of three-alpha (3 alpha) and two-alpha plus Lambda (alpha alpha Lambda) systems, using two-cluster resonating-group method kernels. The input includes an effective two-nucleon force for the alpha alpha resonating-group method and a new effective Lambda N force for the Lambda alpha interaction. The latter force is a simple two-range Gaussian potential for each spin-singlet and triplet state, generated from the phase-shift behavior of the quark-model hyperon-nucleon interaction, fss2, by using an inversion method based on supersymmetric quantum mechanics. Owing to the exact treatment of the Pauli-forbidden states between the clusters, the present three-cluster Faddeev formalism can describe the mutually related, alpha alpha, 3 alpha and alpha alpha Lambda systems, in terms of a unique set of the baryon-baryon interactions. For the three-range Minnesota force which describes the alpha alpha phase shifts quite accurately, the ground-state and excitation energies of 9Be Lambda are...

  17. Production of β-globin and adult hemoglobin following G418 treatment of erythroid precursor cells from homozygous β039 thalassemia patients

    Science.gov (United States)

    Salvatori, Francesca; Breveglieri, Giulia; Zuccato, Cristina; Finotti, Alessia; Bianchi, Nicoletta; Borgatti, Monica; Feriotto, Giordana; Destro, Federica; Canella, Alessandro; Brognara, Eleonora; Lampronti, Ilaria; Breda, Laura; Rivella, Stefano; Gambari, Roberto

    2013-01-01

    In several types of thalassemia (including β039-thalassemia), stop codon mutations lead to premature translation termination and to mRNA destabilization through nonsense-mediated decay. Drugs (for instance aminoglycosides) can be designed to suppress premature termination, inducing a ribosomal readthrough. These findings have introduced new hopes for the development of a pharmacologic approach to the cure of this disease. However, the effects of aminoglycosides on globin mRNA carrying β-thalassemia stop mutations have not yet been investigated. In this study, we have used a lentiviral construct containing the β039- thalassemia globin gene under control of the β-globin promoter and a LCR cassette. We demonstrated by fluorescence-activated cell sorting (FACS) analysis the production of β-globin by K562 cell clones expressing the β039-thalassemia globin gene and treated with G418. More importantly, after FACS and high-performance liquid chromatography (HPLC) analyses, erythroid precursor cells from β039-thalassemia patients were demonstrated to be able to produce β-globin and adult hemoglobin after treatment with G418. This study strongly suggests that ribosomal readthrough should be considered a strategy for developing experimental strategies for the treatment of β0-thalassemia caused by stop codon mutations. PMID:19810011

  18. Production of beta-globin and adult hemoglobin following G418 treatment of erythroid precursor cells from homozygous beta(0)39 thalassemia patients.

    Science.gov (United States)

    Salvatori, Francesca; Breveglieri, Giulia; Zuccato, Cristina; Finotti, Alessia; Bianchi, Nicoletta; Borgatti, Monica; Feriotto, Giordana; Destro, Federica; Canella, Alessandro; Brognara, Eleonora; Lampronti, Ilaria; Breda, Laura; Rivella, Stefano; Gambari, Roberto

    2009-11-01

    In several types of thalassemia (including beta(0)39-thalassemia), stop codon mutations lead to premature translation termination and to mRNA destabilization through nonsense-mediated decay. Drugs (for instance aminoglycosides) can be designed to suppress premature termination, inducing a ribosomal readthrough. These findings have introduced new hopes for the development of a pharmacologic approach to the cure of this disease. However, the effects of aminoglycosides on globin mRNA carrying beta-thalassemia stop mutations have not yet been investigated. In this study, we have used a lentiviral construct containing the beta(0)39-thalassemia globin gene under control of the beta-globin promoter and a LCR cassette. We demonstrated by fluorescence-activated cell sorting (FACS) analysis the production of beta-globin by K562 cell clones expressing the beta(0)39-thalassemia globin gene and treated with G418. More importantly, after FACS and high-performance liquid chromatography (HPLC) analyses, erythroid precursor cells from beta(0)39-thalassemia patients were demonstrated to be able to produce beta-globin and adult hemoglobin after treatment with G418. This study strongly suggests that ribosomal readthrough should be considered a strategy for developing experimental strategies for the treatment of beta(0)-thalassemia caused by stop codon mutations. Am. J. Hematol., 2009. (c) 2009 Wiley-Liss, Inc.

  19. The effect of some medical treatments of thalassemia on the red blood cells

    Science.gov (United States)

    Zhang, Xiufang; Shen, Linming; Bao, Hongxia; Din, Xiaolan; Wang, Rongxin; Liu, Yuanyuan; Gao, Naifei; Huang, Youwen

    1992-04-01

    The Mössbauer spectroscopy (MS) and circular dichroism (CD) measurements have been used to investigate the effect of some medical treatments on the red blood cells (RBCs) of the patients with HbH discase and β-thalassemia (Thal.) major, respectively. The results indicate that both splenectomy and treatment with myleran are effective to alleviate the symptoms of anemia for some patients, but both of them are different in the effect on the RBCs of the patients. On the basis of the results, a hypothesis on the course of denaturation in hemoglobin (Hb) of the patients is proposed.

  20. Extramedullary Hematopoiesis in a Man With β-Thalassemia: An Uncommon Cause of an Adrenal Mass

    Directory of Open Access Journals (Sweden)

    Zeighami

    2015-06-01

    Full Text Available Introduction Extramedullary hematopoiesis (EMH commonly occurs in the spleen, liver and lymph nodes. Rare cases of EMH in the adrenal gland have been reported. Case Presentation We report the case of a 33-year-old man from the South of Iran suffering from major β-thalassemia, who underwent open left adrenalectomy and the histopathology revealed EMH. Conclusions In patients in which a history of hematologic disorders exists, careful imaging and hormonal assay should be done to certify a diagnosis of EMH. However, the surgical management becomes inevitable in certain cases.

  1. Iron metabolism and ineffective erythropoiesis in beta-thalassemia mouse models.

    Science.gov (United States)

    Ramos, Pedro; Melchiori, Luca; Gardenghi, Sara; Van-Roijen, Nico; Grady, Robert W; Ginzburg, Yelena; Rivella, Stefano

    2010-08-01

    beta-thalassemia is a disease associated with decreased beta-globin production leading to anemia, ineffective erythropoiesis, and iron overload. New mechanisms associated with modulation of erythropoiesis and iron metabolism have recently been discovered in thalassemic mice, improving our understanding of the pathophysiology of this disease. These discoveries have the potential to be translated into clinically-relevant therapeutic options to reduce ineffective erythropoiesis and iron overload. A new generation of therapies based on limiting ineffective erythropoiesis, iron absorption, and the correction of iron maldistribution could be on the way, possibly complementing and improving the current standard of patient care.

  2. Iron metabolism and ineffective erythropoiesis in β-thalassemia mouse models

    Science.gov (United States)

    Ramos, Pedro; Melchiori, Luca; Gardenghi, Sara; Van-Roijen, Nico; Grady, Robert W.; Ginzburg, Yelena; Rivella, Stefano

    2013-01-01

    β-thalassemia is a disease associated with decreased β-globin production leading to anemia, ineffective erythropoiesis, and iron overload. New mechanisms associated with modulation of erythropoiesis and iron metabolism have recently been discovered in thalassemic mice, improving our understanding of the pathophysiology of this disease. These discoveries have the potential to be translated into clinically-relevant therapeutic options to reduce ineffective erythropoiesis and iron overload. A new generation of therapies based on limiting ineffective erythropoiesis, iron absorption, and the correction of iron maldistribution could be on the way, possibly complementing and improving the current standard of patient care. PMID:20712768

  3. PET CT imaging in extramedullary hematopoiesis and lung cancer surprise in a case with thalassemia intermedia

    Directory of Open Access Journals (Sweden)

    Semra Paydaş

    2011-03-01

    Full Text Available Extramedullary hematopoiesis (EMH is the production of hematopoietic precursors outside the bone marrow cavity, and it causes mass effects according to its localization. Magnetic resonance imaging (MRI and/or computed tomography (CT scans are used most commonly to detect EMH foci. We report herein a case with thalassemia intermedia causing paravertebral mass associated with EMH detected by CT scan. We further evaluated the case with positron emission tomography (PET CT, and lung cancer, which was not revealed in the CT scan, was detected coincidentally.

  4. 42 CFR 418.309 - Hospice cap amount.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false Hospice cap amount. 418.309 Section 418.309 Public...) MEDICARE PROGRAM HOSPICE CARE Payment for Hospice Care § 418.309 Hospice cap amount. The hospice cap amount... until October 31 of the following year. (b) Each hospice's cap amount is calculated by the...

  5. 75 FR 49527 - Caps Visual Communications, LLC; Black Dot Group; Formerly Known as Caps Group Acquisition, LLC...

    Science.gov (United States)

    2010-08-13

    ... Employment and Training Administration Caps Visual Communications, LLC; Black Dot Group; Formerly Known as... Adjustment Assistance on June 24, 2010, applicable to workers of Caps Visual Communications, LLC, Black Dot..., Caps Visual Communications, LLC, Black Dot Group, formerly known as Caps Group Acquisition,...

  6. The entire β-globin gene cluster is deleted in a form of τδβ-thalassemia.

    NARCIS (Netherlands)

    E.R. Fearon; H.H.Jr. Kazazian; P.G. Waber (Pamela); J.I. Lee (Joseph); S.E. Antonarakis; S.H. Orkin (Stuart); E.F. Vanin; P.S. Henthorn; F.G. Grosveld (Frank); A.F. Scott; G.R. Buchanan

    1983-01-01

    textabstractWe have used restriction endonuclease mapping to study a deletion involving the beta-globin gene cluster in a Mexican-American family with gamma delta beta-thalassemia. Analysis of DNA polymorphisms demonstrated deletion of the beta-globin gene from the affected chromosome. Using a DNA f

  7. Improvements in the HbVar database of human hemoglobin variants and thalassemia mutations for population and sequence variation studies.

    NARCIS (Netherlands)

    G.P. Patrinos (George); B. Giardine (Belinda); C. Riemer (Cathy); W. Miller (Webb); D.H. Chui (David); N.P. Anagnou (Nicholas); H. Wajcman (Henri); R.C. Hardison (Ross)

    2004-01-01

    textabstractHbVar (http://globin.cse.psu.edu/globin/hbvar/) is a relational database developed by a multi-center academic effort to provide up-to-date and high quality information on the genomic sequence changes leading to hemoglobin variants and all types of thalassemia and hemogl

  8. Targeted correction of a thalassemia-associated beta-globin mutation induced by pseudo-complementary peptide nucleic acids

    DEFF Research Database (Denmark)

    Lonkar, Pallavi; Kim, Ki-Hyun; Kuan, Jean Y

    2009-01-01

    Beta-thalassemia is a genetic disorder caused by mutations in the beta-globin gene. Triplex-forming oligonucleotides and triplex-forming peptide nucleic acids (PNAs) have been shown to stimulate recombination in mammalian cells via site-specific binding and creation of altered helical structures...

  9. Study of the effect of iron overload on the function of endocrine glands in male thalassemia patients

    Directory of Open Access Journals (Sweden)

    Abdulzahra Mohammed

    2011-01-01

    Full Text Available Background: Iron overload is an important issue in the state of thalassemic patients due to the harmful effect of high concentration of iron deposited in different tissues in human body including endocrine glands. In the present work, an attempt is carried out to estimate the effect of iron overload in thalassemic patients on the function of endocrine glands through the estimation of their ability to secrete adequate amounts of certain hormones. Materials and Methods: Seventy eight male children with beta-thalassemia, in the age-group of 4-11 years, were enrolled for this research. These children were being treated with frequent transfusions and long-term iron chelation therapy. Thirty age and sex matched children without thalassemia constituted the control group. Ferritin and different hormones were estimated by ELISA technique. Results: The results showed a mild reduction in the function of endocrine glands through the decrease in the level of some hormones. These changes due mainly to the hypoxia and precipitation of iron in certain glands and overlapping with the synthesis or secretion of the hormones. Conclusion: There is a different hormonal disturbances in beta thalassemia patients. Reduction of total body iron store is an important goal of the treatment of thalassemia and measuring the hormones concentration is necessary for the follow up of the thalassemic patients especially during puberty.

  10. Generation and Characterization of a Transgenic Mouse Carrying a Functional Human β -Globin Gene with the IVSI-6 Thalassemia Mutation.

    Science.gov (United States)

    Breveglieri, Giulia; Mancini, Irene; Bianchi, Nicoletta; Lampronti, Ilaria; Salvatori, Francesca; Fabbri, Enrica; Zuccato, Cristina; Cosenza, Lucia C; Montagner, Giulia; Borgatti, Monica; Altruda, Fiorella; Fagoonee, Sharmila; Carandina, Gianni; Rubini, Michele; Aiello, Vincenzo; Breda, Laura; Rivella, Stefano; Gambari, Roberto; Finotti, Alessia

    2015-01-01

    Mouse models that carry mutations causing thalassemia represent a suitable tool to test in vivo new mutation-specific therapeutic approaches. Transgenic mice carrying the β-globin IVSI-6 mutation (the most frequent in Middle-Eastern regions and recurrent in Italy and Greece) are, at present, not available. We report the production and characterization of a transgenic mouse line (TG-β-IVSI-6) carrying the IVSI-6 thalassemia point mutation within the human β-globin gene. In the TG-β-IVSI-6 mouse (a) the transgenic integration region is located in mouse chromosome 7; (b) the expression of the transgene is tissue specific; (c) as expected, normally spliced human β-globin mRNA is produced, giving rise to β-globin production and formation of a human-mouse tetrameric chimeric hemoglobin (mu) α-globin2/(hu) β-globin2 and, more importantly, (d) the aberrant β-globin-IVSI-6 RNAs are present in blood cells. The TG-β-IVSI-6 mouse reproduces the molecular features of IVSI-6 β-thalassemia and might be used as an in vivo model to characterize the effects of antisense oligodeoxynucleotides targeting the cryptic sites responsible for the generation of aberrantly spliced β-globin RNA sequences, caused by the IVSI-6 mutation. These experiments are expected to be crucial for the development of a personalized therapy for β-thalassemia.

  11. Molecular mechanisms associated with increased fetal hemoglobin G gamma-type in part-aboriginal family with beta thalassemia.

    Science.gov (United States)

    Motum, P I; Lammi, A; Trent, R J

    1989-07-01

    A part-Aboriginal family with beta thalassemia and raised hemoglobin F (HbF) was studied at the molecular level to determine if there were identifiable gene changes associated with increased production of HbF. Two beta thalassemia heterozygotes aged eight years and 18 months had raised HbF levels of 2.9% and 22% respectively. HbF was predominantly G gamma in composition. Five family members were typed for restriction fragment length polymorphisms (RFLPs) using nine restriction enzymes and five DNA probes specific for the beta globin cluster on chromosome 11. RFLPs were combined to construct haplotypes for the beta thalassemia and the high HbF defects. A beta globin subhaplotype comprising only 5' RFLP markers (-(+)-(+) +) co-segregated with the high HbF determinant. This has previously been associated with increased G gamma expression in beta thalassemia and sickle cell anemia. An additional Xmnl RFLP 5' to the G gamma gene, which has been described in individuals with elevated G gamma expression, was also demonstrated in those family members with increased G gamma levels. In this study both the 5' beta globin subhaplotype (-(+)-(+) +) and the Xmnl/gamma RFLP are present in the one family but the relative contributions of each cannot be determined.

  12. Resolution of alloimmunization and refractory autoimmune hemolytic anemia in a multi-transfused beta-thalassemia major patient

    Directory of Open Access Journals (Sweden)

    Joseph Philip

    2014-01-01

    Full Text Available Beta-thalassemia is one of the most prevalent autosomal disorders, which affect more than 400,000 newborn per year worldwide. In India, the carrier rate of beta-thalassemia varies from 3-17%. The overall rate of alloimmunization in thalassemia patients has been reported to be 5-30% in the world, which is mostly contributed by the alloimmunization to minor blood group antigen. Among Asians, the incidence of red cell alloimmunization is 22%. The recommended treatment for beta-thalassemia major is regular blood transfusion every 3 to 4 weeks. The development of anti-red cell antibodies (alloantibodies and/or autoantibodies can significantly complicate transfusion therapy. Alloantibodies are commonly associated with red cell hemolysis. Red cell autoantibodies appear less frequently, but they can result in clinical hemolysis called autoimmune hemolytic anemia (AIHA, and in difficulty in cross-matching blood. Patients with autoantibodies may have a higher transfusion rate and often require immunosuppressive drugs or alternative treatments including intravenous immunoglobulin (IVIg and rituximab (anti-CD20 monoclonal antibody.

  13. Resveratrol: Antioxidant activity and induction of fetal hemoglobin in erythroid cells from normal donors and β-thalassemia patients.

    Science.gov (United States)

    Fibach, Eitan; Prus, Eugenia; Bianchi, Nicoletta; Zuccato, Cristina; Breveglieri, Giulia; Salvatori, Francesca; Finotti, Alessia; Lipucci di Paola, Michele; Brognara, Eleonora; Lampronti, Ilaria; Borgatti, Monica; Gambari, Roberto

    2012-06-01

    Thalassemia and sickle-cell anemia (SCA) present a major public health problem in countries where the number of carriers and affected individuals is high. As a result of the abnormalities in hemoglobin production, cells of thalassemia and SCA patients exhibit oxidative stress, which ultimately is responsible for the chronic anemia observed. Therefore, identification of compounds exhibiting both antioxidant and hemoglobin-inducing activities is highly needed. Our results demonstrate resveratrol to be such a compound. This was shown both in the human K562 cell line, as well as in erythroid precursors derived from normal donors and β-thalassemia patients. Resveratrol was shown to exhibit antioxidant activity and to stimulate the expression of the γ-globin genes and the accumulation of fetal hemoglobin (HbF). To the best of our knowledge, this is the first report pointing to such a double effect of resveratrol. Since this natural product is already marketed as an antioxidant, future investigations should concentrate on demonstrating its potential to augment HbF production in experimental animal models (e.g., thalassemia and SCA mice) as well as in patients. We believe that the potential of clinical use of resveratrol as an antioxidant and HbF stimulator may offer a simple and inexpensive treatment to patients.

  14. Scenarios for a cap beyond 2013; Implications for EU27 agriculture and the cap budget

    NARCIS (Netherlands)

    Helming, J.F.M.; Terluin, I.J.

    2011-01-01

    An ex ante analysis of a set of five policy components (proposed post 2013 CAP measures) has been carried out for the 2014-2020 period, based on the EC Communication The CAP towards 2020 of 18 November 2010. The policy components are defined in such a way that they focus on the contribution of farme

  15. Storage of cellular 5' mRNA caps in P bodies for viral cap-snatching.

    Science.gov (United States)

    Mir, M A; Duran, W A; Hjelle, B L; Ye, C; Panganiban, A T

    2008-12-09

    The minus strand and ambisense segmented RNA viruses include multiple important human pathogens and are divided into three families, the Orthomyxoviridae, the Bunyaviridae, and the Arenaviridae. These viruses all initiate viral transcription through the process of "cap-snatching," which involves the acquisition of capped 5' oligonucleotides from cellular mRNA. Hantaviruses are emerging pathogenic viruses of the Bunyaviridae family that replicate in the cytoplasm of infected cells. Cellular mRNAs can be actively translated in polysomes or physically sequestered in cytoplasmic processing bodies (P bodies) where they are degraded or stored for subsequent translation. Here we show that the hantavirus nucleocapsid protein binds with high affinity to the 5' cap of cellular mRNAs, protecting the 5' cap from degradation. We also show that the hantavirus nucleocapsid protein accumulates in P bodies, where it sequesters protected 5' caps. P bodies then serve as a pool of primers during the initiation of viral mRNA synthesis by the viral polymerase. We propose that minus strand segmented viruses replicating in the cytoplasm have co-opted the normal degradation machinery of P bodies for storage of cellular caps. Our data also indicate that modification of the cap-snatching model is warranted to include a role for the nucleocapsid protein in cap acquisition and storage.

  16. A monozygotic twin pair with β-thalassemia carrier status in a Dudh Kharia tribal family of Orissa

    Directory of Open Access Journals (Sweden)

    Balgir R

    2007-01-01

    Full Text Available Background: The β -thalassemia syndrome is a genetically inherited commonly encountered hematological disorder in the state of Orissa. It causes high degree of morbidity, mortality and fetal wastage in the poor vulnerable people. Aims and Objectives: There is an equal probability (50% chance in every singleton pregnancy that a carrier parent of β -thalassemia major would either bear normal or carrier offspring, but not two offspring with carrier of β -thalassemia major genotype together. For the first time, a carrier parent of β -thalassemia major gene has born progeny (three daughters and a twin male offspring with a carrier status of β -thalassemia major in Dudh Kharia tribal family studied from Sundargarh district of Orissa. Materials and Methods: We screened randomly selected population of Dudh Kharia tribe from Sundargarh district of Orissa for hemoglobinopathies to assess the extent of the problem, design possible interventions and provide genetic counseling to them. A family with twin children was identified during screening in Lata Gaon in Bargaon block of Sundargarh district of Orissa for the above-mentioned study. Background information for this family such as name, age, sex, tribe, native place, reproductive history, family pedigree and clinical signs and symptoms were also recorded. Standardized genetic and hematological procedures and techniques were followed for analysis. Results: Laboratory investigations for alkaline electrophoresis of blood lysate on cellulose acetate membrane showed raised hemoglobin A 2 level in mother (Hb A 2 = 5.3%, in three daughters (Hb A 2 =6.5, 5.9, 5.5% in chronological and birth order, in two twin sons (Hb A 2 =5.9% and 6.0% and normal (Hb A 2 = 3.3% for father. Hence, all the children i.e., three daughters and two twin sons, including the mother were β -thalassemia carriers. Since all the hematological parameters i.e., red cell indices, G-6-PD enzyme activity, ABO and Rhesus blood groups and

  17. Which psychosocial factors are related to chelation adherence in thalassemia? A systematic review.

    Science.gov (United States)

    Evangeli, Michael; Mughal, Kulsoom; Porter, John B

    2010-06-01

    Good adherence to iron chelation therapy in thalassemia is crucial. Although there is evidence that adherence is related to regimen factors, there has been less emphasis on the relationship between psychosocial (psychological, demographic and social) factors and adherence. We present a systematic review of psychosocial correlates of chelation adherence in thalassemia. Nine studies met the inclusion criteria. Information was extracted regarding the study characteristics and the relationship between psychosocial factors and chelation adherence. Methodological quality was rated. The studies took place in a range of countries, were mostly cross sectional in design, and examined adherence to deferoxamine (DFO) only. Sample sizes ranged from 15 to 1573. A variety of psychosocial variables were examined. Definitions of adherence varied between studies and non adherence rates were also variable (9 to 66%). Older age was consistently associated with lower levels of chelation adherence. There were few other consistent findings. The methodological quality of studies was variable. There is a need for more methodologically sophisticated and theoretically informed studies on psychosocial correlates of chelation adherence. We offer specific suggestions.