High Prevalence Of α-thalassemia Among Individuals With Microcytosis And Hypochromia Without Anemia

In order to determine the contribution of α-thalassemia to microcytosis and hypochromia, 339 adult outpatients seen at Unicamp University Hospital (with the exception of the Clinical Hematology outpatient clinics), who showed normal hemoglobin (Hb) levels and reduced mean corpuscular volume and mean corpuscular hemoglobin, were analyzed. Ninety-eight were Blacks (28.9%) and 241 were Caucasians (71.1%). In all cases, Hb A2 and F levels were either normal or low. The most common deletional and nondeletional forms of α-thalassemia [-α3.7, -α4.2, -MED, -(α)20.5, αHphIα, αNcolα, ααNcoI and αTSAUDI] were investigated by PCR and restriction enzyme analyses. A total of 169 individuals (49.9%) presented α-thalassemia: 145 (42.8%) were heterozygous for the -α3.7 deletion (-α3.7/αα) and 18 (5.3%) homozygous (-α3.7/-α3.7), 5 (1.5%) were heterozygous for the nondeletional form αHPhlα/αα, and 1 (0.3%) was a -MED carrier (-MED/αα). Among the Blacks, 56 (57.1%) showed the -α3.7/ αα genotype, whereas 12 (12.2%) were -α3.7/-α3.7 and I (1.0%) was an αHPhlα carrier; among the Caucasians, 89 (36.9%) were -α3.7/αα, 6 (2.5%) had the -α3.7/-α3.7 genotype, 4 (1.7%) presented the nondeletional form (αHPhlα/αα), and 1 (0.4%) was a -MED carrier. These results demonstrate that α-thalassemia, mainly through the -α3.7 deletion, is an important cause of microcytosis and hypochromia in individuals without anemia. These data are of clinical relevance since these hematological alterations are often interpreted as indicators of iron deficiency.346759762Weatherall, D.J., Clegg, J.G., (1981) The Thalassaemia Syndromes. 3rd Edn., , Blackwell Scientific Publications, OxfordBunn, H.F., Forget, B.G., (1986) Hemoglobin: Molecular, Genetics and Clinical Aspects, , W.B. Saunders, PhiladelphiaHiggs, D.R., Vickers, M.A., Wilkie, A.O.M., Pretorius, I.M., Jarman, A.P., Weatherall, D.J., A review of the molecular genetics of the human α-globin gene cluster (1989) Blood, 73, pp. 1081-1104Kazazian H., Jr., The thalassemia syndromes: Molecular basis and prenatal diagnosis in 1990 (1990) Seminars in Hematology, 27, pp. 209-228Harteveld, K.L., Losekoot, M., Ajgam, H., Van Der Wielen, M., Giordano, P.C., Bernini, L.F., α-Thalassaemia in the Netherlands: A heterogeneous spectrum of both deletions and point mutations (1997) Human Genetics, 100, pp. 465-471Higgs, D.R., α-Thalassaemia (1993) Baillieres Clinical Haematology, 6, pp. 117-150Kattamis, A.C., Camaschella, C., Sivera, P., Surrey, S., Fortina, P., Human α-thalassemia syndromes: Detection of molecular defects (1996) American Journal of Hematology, 53, pp. 81-91Bianco, I., Cappabianca, M.P., Foglietta, E., Lerone, M., Deidda, G., Morlupi, L., Grisanti, P., Graziani, B., Silent thalassemias: Genotypes and phenotypes (1997) Haematologica, 82, pp. 269-280Galanello, R., Sollaino, C., Paglietti, E., Barella, S., Perra, C., Doneddu, I., Pirroni, M.G., Cao, A., α-Thalassemia carrier identification by DNA analysis in the screening for thalassemia (1998) American Journal of Hematology, 59, pp. 273-278Sonati, M.F., Costa, F.F., Hemoglobin Bart's in a Brazilian black population (1990) Brazilian Journal of Medical and Biological Research, 23, pp. 395-396Sonati, M.F., Farah, S.B., Ramalho, A.S., Costa, F.F., High prevalence of α-thalassemia in a Black population of Brazil (1991) Hemoglobin, 15, pp. 309-311Zago, M.A., Costa, F.F., Bottura, C., Hemoglobin H disease in three Brazilian families (1984) Revista Brasileira de Genética, 7, pp. 137-147Wenning, M.R.S.C., Kimura, E.M., Costa, F.F., Saad, S.T.O., Gervásio, S.A., De Jorge, S.B., Borges, E., Sonati, M.F., α-Globin genes: Thalassemic and structural alterations in a Brazilian population (2000) Brazilian Journal of Medical and Biological Research, 33, pp. 1041-1045Dodé, C., Krishnamoorthy, R., Lamb, J., Rochette, J., Rapid analysis of -α3.7 thalassaemia and αααanti 3.7 triplication by enzymatic amplification analysis (1993) British Journal of Haematology, 82, pp. 105-111Bowden, D.K., Vickers, M.A., Higgs, D.R., A PCR-based strategy to detect the common severe determinants of a thalassaemia (1992) British Journal of Haematology, 81, pp. 104-108Oron-Karni, V., Filon, D., Oppenheim, A., Rund, D., Rapid detection of the common Mediterranean α-globin deletions/rearrangements using PCR (1998) American Journal of Hematology, 58, pp. 306-310Hall, G.W., Thein, S.L., Newland, C.A., Chisholm, J.T.S., Kanavakis, E., Kattamis, C., Higgs, D.R., A base substitution (T→C) in codon 29 of the α2-globin gene causes α thalassemia (1993) British Journal of Haematology, 85, pp. 546-552Pearson, H.A., Ehrenkranz, R.A., Rinder, H.M., Hemosiderosis in a normal child secondary to oral iron medication (2000) Pediatrics, 105, pp. 429-43

A Combination Of The -α3.7 And -medii Alleles Causing Hemoglobin H Disease In A Brazilian Patient

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)39180832014/00984-3, FAPESP, Fundação de Amparo à Pesquisa do Estado de São PauloFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

The discoveries of uranium 237 and symmetric fission — From the archival papers of Nishina and Kimura

Shortly before the Second World War time, Nishina reported on a series of prominent nuclear physical and radiochemical studies in collaboration with Kimura. They artificially produced 231Th, a member of the natural actinium series of nuclides, by bombarding thorium with fast neutrons. This resulted in the discovery of 237U, a new isotope of uranium, by bombarding uranium with fast neutrons, and confirmed that 237U disintegrates into element 93 with a mass number of 237. They also identified the isotopes of several middle-weighted elements produced by the symmetric fission of uranium. In this review article, the highlights of their work are briefly summarized along with some explanatory commentaries

Characterization of alpha thalassemic genotypes by multiplex ligation-dependent probe amplification in the Brazilian population

Alpha-thalassemia is the most common inherited disorder of hemoglobin synthesis. Genomic deletions involving the alpha-globin gene cluster on chromosome 16p13.3 are the most frequent molecular causes of the disease. Although common deletions can be detected by a single multiplex gap-PCR, the rare and novel deletions depend on more laborious techniques for their identification. The multiplex ligation-dependent probe amplification (MLPA) technique has recently been used for this purpose and was successfully used in the present study to detect the molecular alterations responsible for the alpha-thalassemic phenotypes in 8 unrelated individuals (3 males and 5 females; age, 4 months to 30 years) in whom the molecular basis of the disease could not be determined by conventional methods. A total of 44 probe pairs were used for MLPA, covering approximately 800 kb from the telomere to the MSLN gene in the 16p13.3 region. Eight deletions were detected. Four of these varied in size from 240 to 720 kb and affected a large region including the entire alpha-globin gene cluster and its upstream regulatory element (alpha-MRE), while the other four varied in size from 0.4 to 100 kb and were limited to a region containing this element. This study is the first in Brazil to use the MLPA method to determine the molecular basis of alpha-thalassemia. The variety of rearrangements identified highlights the need to investigate all cases presenting microcytosis and hypochromia, but without iron deficiency or elevated hemoglobin A2 levels and suggests that these rearrangements may be more frequent in our population than previously estimated.162

Prevalence Of α-thalassemia 3.7 Kb Deletion In The Adult Population Of Rio Grande Do Norte, Brazil

α-Thalassemia, arising from a defect in α-globin chain synthesis, is often caused by deletions involving one or both of the α-genes on the same allele. With the aim of investigating the prevalence of α-thalassemia 3.7 kb deletion in the adult population of Rio Grande do Norte, 713 unrelated individuals, between 18 and 59 years-of-age, were analyzed. Red blood cell indices were electronically determined, and A 2 and F hemoglobins evaluated by HPLC. PCR was applied to the molecular investigation of α-thalassemia 3.7 kb deletion. Eighty (11.2%) of the 713 individuals investigated presented α-thalassemia, of which 79 (11.1%) were heterozygous (-α 3.7/αα) deletions and 1 (0.1%) homozygous (-α 3.7/-α 3.7). Ethnically, heterozygous deletions were higher (24.8%) in Afro-Brazilians. Comparison of hematological parameters between individuals with normal genotype and those with heterozygous α +-thalassemia showed a statistically significant difference in the number of erythrocytes (p < 0.001), MCV (p < 0.001), MCH (p < 0.001) and Hb A 2 (p = 0.007). This study is one of the first dedicated to investigating α-thalassemia 3.7 kb deletion in the population of the State Rio Grande do Norte state. Results obtained demonstrate the importance of investigating this condition in order to elucidate the causes of microcytosis and hypochromia. © 2012, Sociedade Brasileira de Genética. Printed in Brazil.353594598Adorno, E.V., Couto, F.D., Moura Neto, J.P., Menezes, J.F., Rêgo, M., Reis, M.G., Gonçalves, M.S., Hemoglobinopathies in newborns from Salvador, Bahia, Northeast Brazil (2005) Cad Saúde Pública, 21, pp. 292-298Bezerra, C.M., Meissner, R.V., Diagnóstico molecular da talassemia alfa + (deleção-( 3.7) em indivíduos com microcitose e/ou hipocromia atendidos no Hemocentro Dalton Barbosa Cunha em Natal, Rio Grande do Norte (2010) Rev Bras Hematol Hemoter, 32, pp. 90-91. , (Abstract in English)Borg, J., Georgitsi, M., Aleporou-Marinou, V., Kollia, P., Patrinos, G.P., Genetic recombination as a major cause of mutagenesis in the human globin gene clusters (2009) Clin Biochem, 42, pp. 1839-1850Borges, E., Wenning, M.R.S.C., Kimura, E.M., Gervásio, S.A., Costa, F.F., Sonati, M.F., High prevalence of alpha-thalassemia among individuals with microcytosis and hypochromia without anemia (2001) Braz J Med Biol Res, 34, pp. 759-762Cascudo, L.C., (1984) História do Rio Grande do Norte, p. 524. , 2 edition. Fundação José Augusto, NatalCouto, F.D., Albuquerque, A.B.L., Adorno, E.V., Moura Neto, J.P., Freitas, A.L., Oliveira, J.L.B., Reis, M.G., Gonçalves, M.S., Alpha-thalassemia-2, 3.7 kb deletion and hemoglobin AC heterozygosity in pregnancy: A molecular and hematological analysis (2003) Clin Lab Haematol, 25, pp. 29-34Dacie, J.V., Lewis, S.M., (1995) Practical Haematology., p. 608. , Churchill Livingstone, EdinburghDodé, C., Krishnamoorthy, R., Lamb, J., Rochette, J., Rapid analysis of-α 3.7 thalassaemia and ttt anti3.7 triplication by enzymatic amplification analysis (1992) Br J Haematol, 83, pp. 105-111Harteveld, L.C., Higgs, D.R., H-thalassaemia (2010) Orphanet J Rare Dis, 5, pp. 1-21Higgs, D.R., H-Thalassaemia (1993) Baillière's Clin Haematol, 6, pp. 117-150Higgs, D.R., The pathopysiology and clinical features of H thalassemia (2009) Disorders of Hemoglobin, pp. 266-295. , In: Steinberg MH, Forget BG, Higgs DR and Weatherall DJ (eds) 2 nd edition. Cambridge University Press, New YorkHiggs, D.R., Weatherall, D.J., The alpha thalassaemias (2009) Cell Mol Life Sci, 66, pp. 1154-1162Mouélé, R., Pambou, O., Feingold, J., Galactéros, F., M-thalassemia in Bantu population from Congo-Brazzaville: Its interaction with sickle cell anemia (2000) Hum Hered, 50, pp. 118-125Peres, M.J., Romão, L., Carreiro, H., Picanço, I., Batalha, L., Magalhães, H.A., Martins, M.C., Lavinha, J., Molecular basis of H-thalassemia in Portugal (1995) Hemoglobin, 19, pp. 343-352Rahim, F., Microcytic hypochromic anemia patients with thalassemia: Genotyping approach (2009) J Med, 63, pp. 101-108Sankar, V.H., Arya, V., Tewari, D., Gupta, U.R., Pradhan, M., Genotyping of alpha-thalassemia in microcytic hypochromic anemia patients from North India (2006) Indian J Med Res, 47, pp. 391-395Sonati, M.F., Farah, S.B., Ramalho, A.S., Costa, F.F., High prevalence of alpha-thalassemia in a black population of Brazil (1991) Hemoglobin, 15, pp. 309-311Souza, A.E.S., Takanashi, S.Y.L., Cardoso, G., Guerreiro, J.F., S-thalassemia (3.7 kb deletion) in a population from the Brazilian Amazon region: Santarém, Pará State (2009) Genet Mol Res, 8, pp. 477-481Steinberg, M.H., Nagel, R.L., Hemoglobins of the embryo, fetus and adult (2009) Disorders of Hemoglobin, pp. 119-135. , In: Steinberg MH, Forget BG, Higgs DR and Weatherall DJ (eds) 2 nd edition. Cambridge University Press, New YorkWagner, S.C., Castro, S.M., Gonzalez, T.P., Santin, A.P., Filippon, L., Zaleski, C.F., Azevedo, L.A., Hutz, M., Prevalence of common c-thalassemia determinants in south Brazil: Importance for the diagnosis of microcytic anemia (2010) Genet Mol Biol, 33, pp. 641-645Weatherall, D.J., Clegg, J.B., Inherited haemoglobin disorders: An increasing global health problem (2001) Bull World Health Organ, 79, pp. 704-71

Humoral Autoimmune Responses to the Squamous Cell Carcinoma Antigen Protein Family in Psoriasis

Substantial evidence indicates that psoriasis is a T-lymphocyte-mediated autoimmune disease. However, longstanding data also indicate IgG and complement deposition in upper epidermis of psoriasis plaques. This led us to propose that autoantigen–autoantibody interactions in the skin may also be of pathogenic importance. Here, we have confirmed the presence of IgG in upper lesional epidermis and used high-resolution two-dimensional immunoblotting of extracts from this tissue, and laser desorption mass spectrometry of tryptic peptides, to define a series of epidermal proteins that bind IgG from psoriatic serum. The most prominent of these autoantigens are homologues of the serpin, squamous cell carcinoma antigen (SCCA), the other autoantigens identified including arginase 1, enolase 1, and keratin 10. Blood levels of IgG autoantibodies that bind to SCCA proteins were significantly higher in psoriasis than healthy controls (P=0.005), but were not detectable in sera from patients with active atopic dermatitis. To our knowledge, SCCA proteins have not previously been described as autoantigenic in animals or humans and form complexes with IgG that are associated with complement deposition. These findings expose potentially pathogenic humoral immunologic events and thus possible therapeutic targets in psoriasis

Optical properties of dust

http://arxiv.org/abs/0808.4123Except in a few cases cosmic dust can be studied in situ or in terrestrial laboratories, essentially all of our information concerning the nature of cosmic dust depends upon its interaction with electromagnetic radiation. This chapter presents the theoretical basis for describing the optical properties of dust -- how it absorbs and scatters starlight and reradiates the absorbed energy at longer wavelengths.Partial support by a Chandra Theory program and HST Theory Programs is gratefully acknowledged

Superhard Phases of Simple Substances and Binary Compounds of the B-C-N-O System: from Diamond to the Latest Results (a Review)

The basic known and hypothetic one- and two-element phases of the B-C-N-O system (both superhard phases having diamond and boron structures and precursors to synthesize them) are described. The attention has been given to the structure, basic mechanical properties, and methods to identify and characterize the materials. For some phases that have been recently described in the literature the synthesis conditions at high pressures and temperatures are indicated.Comment: Review on superhard B-C-N-O phase

Advances in ab-initio theory of Multiferroics. Materials and mechanisms: modelling and understanding

Within the broad class of multiferroics (compounds showing a coexistence of magnetism and ferroelectricity), we focus on the subclass of "improper electronic ferroelectrics", i.e. correlated materials where electronic degrees of freedom (such as spin, charge or orbital) drive ferroelectricity. In particular, in spin-induced ferroelectrics, there is not only a {\em coexistence} of the two intriguing magnetic and dipolar orders; rather, there is such an intimate link that one drives the other, suggesting a giant magnetoelectric coupling. Via first-principles approaches based on density functional theory, we review the microscopic mechanisms at the basis of multiferroicity in several compounds, ranging from transition metal oxides to organic multiferroics (MFs) to organic-inorganic hybrids (i.e. metal-organic frameworks, MOFs)Comment: 22 pages, 9 figure