SABIIA - Sistema Aberto e Integrado de Informação em Agricultura (Sabiia)

Wenning,M.R.S.C.; Kimura,E.M.; Costa,F.F.; Saad,S.T.O.; Gervásio,S.; de Jorge,S.B.; Borges,E.; Silva,N.M.; Sonati,M.F..

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 -(alpha)20.5 deletions were investigated by PCR, whereas non-deletional alpha-thalassemia (alphaHphalpha, alphaNcoIalpha, <FONT FACE="Symbol">aa</FONT>NcoI, 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 -(alpha)20.5/-alpha3.7 genotype, one had the --MED/-alpha3.7 genotype, one had the --MED/alphaHphalpha genotype and...

Detection of somatic mutations of the PIG-A gene in Brazilian patients with paroxysmal nocturnal hemoglobinuria

Palavras-chave: Alpha-globin genes; Alpha-globin structural variants; Alpha-thalassemia; Hemoglobin H; Hb H disease; Hemoglobin variants; Hemoglobinopathies.

Ano: 2000

URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2000000900008

Franco de Carvalho,R.; Arruda,V.R.; Saad,S.T.O.; Costa,F.F..

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal syndrome characterized by intravascular hemolysis mediated by complement, thrombotic events and alterations in hematopoiesis. Basically, the molecular events which underlie the complexity of the syndrome consist of the absence of the glycosylphosphatidylinositol (GPI) anchor as a consequence of somatic mutations in the PIG-A gene, located on the X chromosome. The GPI group is responsible for the attachment of many proteins to the cytoplasmic membrane. Two of them, CD55 and CD59, have a major role in the inhibition of the action of complement on the cellular membrane of blood cells. The absence of GPI biosynthesis can lead to PNH. Since mutations in the PIG-A gene are always present in patients...

Hemochromatosis (HFE) gene mutations in Brazilian chronic hemodialysis patients

Palavras-chave: Paroxysmal nocturnal hemoglobinuria; Intravascular hemolysis; Complement PIG-A; Mutation.

Ano: 2001

URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2001000600010

Perícole,F.V.; Alves,M.A.V.R.; Saad,S.T.O.; Costa,F.F..

Patients with chronic renal insufficiency (CRI) have reduced hemoglobin levels, mostly as a result of decreased kidney production of erythropoietin, but the relation between renal insufficiency and the magnitude of hemoglobin reduction has not been well defined. Hereditary hemochromatosis is an inherited disorder of iron metabolism. The importance of the association of hemochromatosis with treatment for anemia among patients with CRI has not been well described. We analyzed the frequency of the C282Y and H63D mutations in the HFE gene in 201 Brazilian individuals with CRI undergoing hemodialysis. The analysis of the effects of HFE mutations on iron metabolism and anemia with biochemical parameters was possible in 118 patients of this study (hemoglobin,...

Low expression of APAF-1XL in acute myeloid leukemia may be associated with the failure of remission induction therapy

Palavras-chave: HFE; Chronic renal insufficiency; Anemia; Iron metabolism.

Ano: 2005

URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2005000900005

Benites,B.D.; Fattori,A.; Hackel,C.; Lorand-Metze,I.; De Souza,C.A.; Schulz,E.; Costa,F.F.; Saad,S.T.O..

Apoptotic protease activating factor 1 (APAF-1) has a critical role in the regulation of apoptosis. In the present study, the mRNA expression analysis of different APAF-1 transcripts (APAF-1S, APAF-1LC, APAF-1LN, and APAF-1XL) was analyzed in bone marrow samples from 37 patients with acute myeloid leukemia (newly diagnosed, with no previous treatment). APAF-1XL and APAF-1LN transcripts (with and without an extra WD-40 repeat region, respectively) were detected in all samples, although the major form expressed was APAF-1XL in 65% of the samples (group 1), while 35% of the samples expressed primarily APAF-1LN (group 2). Only 46% of the patients presented complete remission in response to remission induction therapy (represented by less than 5% marrow blasts...

Minimal doses of hydroxyurea for sickle cell disease

Palavras-chave: APAF-1; Acute myeloid leukemia; Apoptosis; Chemotherapy resistance.

Ano: 2008

URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2008000700004

Lima,C.S.P.; Arruda,V.R.; Costa,F.F.; Saad,S.T.O..

The use of hydroxyurea (HU) can improve the clinical course of sickle cell disease. However, several features of HU treatment remain unclear, including the predictability of drug response and determination of adequate doses, considering positive responses and minimal side effects. In order to identify adequate doses of HU for treatment of sickle cell disease, 10 patients, 8 with sickle cell anemia and 2 with Sß thalassemia (8SS, 2Sß), were studied for a period of 6 to 19 months in an open label dose escalation trial (10 to 20 mg kg-1 day-1). Hemoglobin (Hb), fetal hemoglobin (Hb F) and mean corpuscular volume (MCV) values and reticulocyte, neutrophil and platelet counts were performed every two weeks during the increase of the HU dose and every 4 weeks...

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

Palavras-chave: Sickle cell disease; Hydroxyurea; Hemoglobinopathy.

Ano: 1997

URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X1997000800004

Andrade,T.G. de; Fattori,A.; Saad,S.T.O.; Sonati,M.F.; Costa,F.F..

We describe the clinical and molecular characteristics of two unrelated Brazilian families with an association of the Sicilian form of (dß)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 observed in the DNA of carriers of Sicilian (dß)º-thalassemia. The nucleotide sequence of this fragment confirmed the Sicilian deletion. There are few reports concerning the Hb S/(dß)º-thalassemia association and patient 2 is the first reported case of Sicilian type of...

ß-Spectrin São PauloII, a novel frameshift mutation of the ß-spectrin gene associated with hereditary spherocytosis and instability of the mutant mRNA

Palavras-chave: Thalassemia; Sickle cell; Hereditary persistence of fetal hemoglobin; Globin genes; Sicilian thalassemia.

Ano: 2002

URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2002000800003

Bassères,D.S.; Tavares,A.C.; Costa,F.F.; Saad,S.T.O..

Hereditary spherocytosis (HS) is a common inherited anemia characterized by the presence of spherocytic red cells. Defects in several membrane protein genes have been involved in the pathogenesis of HS. ß-Spectrin-related HS seems to be common. We report here a new mutation in the ß-spectrin gene coding region in a patient with hereditary spherocytosis. The patient presented acanthocytosis and spectrin deficiency and, at the DNA level, a novel frameshift mutation leading to HS, i.e., a C deletion at codon 1392 (ß-spectrin São PauloII), exon 20. The mRNA encoding ß-spectrin São PauloII was very unstable and the mutant protein was not detected in the membrane or in other cellular compartments. It is interesting to note that frameshift mutations of the...

The Agamma-195 (C->G) mutation in hereditary persistence of fetal hemoglobin is not associated with activation of a reporter gene in vitro

Palavras-chave: SS-Spectrin; Red cell membrane; Spherocytosis; Acanthocytes; Mutation.

Ano: 2002

URL: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2002000800009

Schreiber,R.; Gonçalves,M.S.; Junqueira,M.L.; Saad,S.T.O.; Krieger,J.E.; Costa,F.F..

Hereditary persistence of fetal hemoglobin is an uncommon, benign disorder in which the expression of gamma-globin genes persists into adult life. Several point mutations have been associated with the increased gamma-globin gene promoter activity. We evaluated the -195 (C->G) mutation by a functional in vitro assay based on the luciferase reporter gene system. The results indicated that the increased promoter activity observed in vivo could not be reproduced in vitro under the conditions employed, suggesting that other factors may be involved in the overexpression of the gamma-globin gene containing the -195 (C->G) mutation. Furthermore, this is the first time that the -195 (C->G) mutation of the Agamma-globin gene has been evaluated by in vitro...