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926 results on '"Luzzatto, L"'

101. Molecular basis of chronic non-spherocytic haemolytic anaemia: a new G6PD variant (393 Arg----His) with abnormal KmG6P and marked in vivo instability

Author

Filosa S., Calabrò V., Vallone D., Poggi V., Mason P., Pagnini D., Alfinito F., Rotoli B., Martini G., Luzzatto L., and Battistuzzi G.

Subjects
congenital, hereditary, and neonatal diseases and abnormalities, hemic and lymphatic diseases, parasitic diseases
Abstract

More than 80 genetic variants of glucose-6-phosphate dehydrogenase (G6PD) are associated with chronic non-spherocytic haemolytic anaemia (CNSHA). In order to help clarify the molecular basis of this association, we have carried out a detailed biochemical and genetic characterization of two G6PD deficient brothers affected by CNSHA. The G6PD from the two patients has altered electrophoretic mobility, abnormally elevated Michaelis constant (Km) for G6P, and extreme instability in vivo and in vitro. By comparison with published information we found that this is a new G6PD variant which we have designated G6PD Portici. The entire coding region of the gene has been sequenced, and a single point mutation, a G----A transition, was found at position 1178 in exon X, causing a substitution of histidine for arginine at residue 393 in the polypeptide chain. By polymerase chain reaction (PCR) amplification followed by diagnostic restriction enzyme analysis and allele-specific oligonucleotide hybridization we have demonstrated the inheritance of this mutation in the patient's family. Our results support the notion of a causative link between this mutation in the G6PD gene and CNSHA. Our data, in combination with previous data in the literature, suggest that the three-dimensional structure of G6PD is such as to cause interaction in the binding of its two substrates, G6P and NADP.

Published
1992

102. OP04 Safety and efficacy of the terminal complement inhibitor eculizumab in patients with paroxysmal nocturnal hemoglobinuria: Shepherd Phase III clinical study results

Author

Muus, P., primary, Luzzatto, L., additional, Rotoli, B., additional, Young, N.S., additional, Schubert, J., additional, Urbano-Ispizua, A., additional, Coyle, L., additional, DeCastro, C., additional, Fu, C.L., additional, Maciejewski, J.P., additional, Kroon, H.A., additional, Rother, R.P., additional, Hillmen, P., additional, and Schrezenmeier, H., additional

Published
2007
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107. Protection against malaria morbidity - near-fixation of the alpha-thalassemia gene in a Nepalese population

Author

Modiano, G, Morpurgo, G, Terrenato, L, Novelletto, A, Di Rienzo, A, Colombo, B, Purpura, M, Mariani, M, Santachiara Benerecetti, S, Brega, A, Dixit, K, Shrestha, S, Lania, A, Wanachiwanawin, W, and Luzzatto, L

Subjects
Electrophoresis, Genetic Markers, thalassemia, Heterozygote, alpha thalassemia, article, ethnic group, genotype, human, infection resistance, malaria, nepal, normal human, priority journal, Animal, Blotting, Southern, DNA, Electrophoresis, Cellulose Acetate, Erythrocytes, Homozygote, Malaria, Nepal, Phenotype, Plasmodium falciparum, Support, Non-U.S. Gov't, Thalassemia, Non-U.S. Gov't, Southern, Cellulose Acetate, Blotting, Settore BIO/18 - Genetica, Support
Published
1991

108. Origin and spread of the glucose-6-phosphate dehydrogenase variant (G6PD-Mediterranean) in the Middle East

Author

Kurdi-Haidar, B, Mason, P J, Berrebi, A, Ankra-Badu, G, al-Ali, A, Oppenheim, A, and Luzzatto, L

Subjects
Male, Base Sequence, Molecular Sequence Data, Restriction Mapping, Genetic Variation, Glucosephosphate Dehydrogenase, Pedigree, Middle East, Glucosephosphate Dehydrogenase Deficiency, Phenotype, hemic and lymphatic diseases, parasitic diseases, Mutation, Mediterranean Sea, Humans, Female, Polymorphism, Restriction Fragment Length, Research Article
Abstract

A common glucose-6-phosphate dehydrogenase (G6PD) variant characterized by severe enzyme deficiency and B-like electrophoretic mobility is called "G6PD-Mediterranean" because it is found in different populations around the Mediterranean Sea. Sequence analysis of Italian subjects has revealed that the molecular basis of G6PD-Mediterranean is a single C-T transition at nucleotide position 563, causing a serine phenylalanine replacement at amino acid position 188. Most G6PD-Mediterranean subjects also have a silent C-T transition (without amino acid replacement) at nucleotide position 1311. Twenty-one unrelated individuals from Saudi Arabia, Iraq, Iran, Jordan, Lebanon, and Israel with both severe G6PD deficiency and B-like electrophoretic mobility were tested for both mutations by using amplification followed by digestion with appropriate restriction enzymes. All but one had the 563 mutation, and, of these, all but one had the 1311 mutation. Another 24 unrelated Middle Eastern individuals with normal G6PD activity or not known to be G6PD deficient were similarly tested. Four had the silent mutation at position 1311 in the absence of the deficiency mutation at position 563. We conclude that (1) the large majority of Middle Eastern subjects with the G6PD-Mediterranean phenotype have the same mutation found in Italy, (2) the silent mutation is an independent polymorphism in the Middle East, with a frequency of about .13, and (3) the mutation leading to the G6PD-Mediterranean deficiency has probably arisen on a chromosome that already carried the silent mutation.

Published
1990

110. Targeted disruption of the housekeeping gene encoding glucose 6-phosphate dehydrogenase (G6PD-null): G6PD is dispensable for pentose synthesis but essential for defense against oxidative stress.

Author

Pandolfi, P.P., Sonati, F., Rivi, R., Mason, P., Grosveld, F.G. (Frank), Luzzatto, L., Pandolfi, P.P., Sonati, F., Rivi, R., Mason, P., Grosveld, F.G. (Frank), and Luzzatto, L.

Abstract

Glucose 6-phosphate dehydrogenase (G6PD) is a housekeeping enzyme encoded in mammals by an X-linked gene. It has important functions in intermediary metabolism because it catalyzes the first step in the pentose phosphate pathway and provides reductive potential in the form of NADPH. In human populations, many mutant G6PD alleles (some present at polymorphic frequencies) cause a partial loss of G6PD activity and a variety of hemolytic anemias, which vary from mild to severe. All these mutants have some residual enzyme activity, and no large deletions in the G6PD gene have ever been found. To test which, if any, function of G6PD is essential, we have disrupted the G6PD gene in male mouse embryonic stem cells by targeted homologous recombination. We have isolated numerous clones, shown to be recombinant by Southern blot analysis, in which G6PD activity is undetectable. We have extensively characterized individual clones and found that they are extremely sensitive to H2O2 and to the sulfydryl group oxidizing agent, diamide. Their markedly impaired cloning efficiency is restored by reducing the oxygen tension. We conclude that G6PD activity is dispensable for pentose synthesis, but is essential to protect cells against even mild oxidative stress.

Published
1995

113. Tissue-specific Regulation of Human Glucose-6-phosphate-dehydrogenase (g6pd) Gene-transcription

Author

UCL - Cliniques universitaires Saint-Luc, UCL - MD/BICL - Département de biochimie et de biologie cellulaire, Philippe, Marianne, Lemaigre, Frédéric, Martini, G., Mason, PJ., Luzzatto, L., Rousseau, GG., UCL - Cliniques universitaires Saint-Luc, UCL - MD/BICL - Département de biochimie et de biologie cellulaire, Philippe, Marianne, Lemaigre, Frédéric, Martini, G., Mason, PJ., Luzzatto, L., and Rousseau, GG.

Published
1993

114. A transgenic mouse model of sickle cell disorder.

Author

Greaves, D.R. (David), Fraser, P.J. (Peter), Vidal, M.A., Hedges, M.J., Ropers, D., Luzzatto, L., Grosveld, F.G. (Frank), Greaves, D.R. (David), Fraser, P.J. (Peter), Vidal, M.A., Hedges, M.J., Ropers, D., Luzzatto, L., and Grosveld, F.G. (Frank)

Abstract

A single base-pair mutation (beta s) in codon 6 of the human beta-globin gene, causing a single amino-acid substitution, is the cause of sickle cell anaemia. The mutant haemoglobin molecule, HbS, polymerizes when deoxygenated and causes deformation of the erythrocytes to a characteristic 'sickled' shape. Sickling of cells in small vessels causes painful crises and other life-threatening complications. Although the molecular basis for sickle cell anaemia has been known for 30 years, no definitive treatment is available. An animal model of sickle cell anaemia would not only allow a detailed analysis of the factors that initiate erythrocyte sickling in vivo and of the pathophysiology of the disease, but would also permit the development of novel approaches to the treatment of the disease. By using the dominant control region sequences from the human beta-globin locus, together with human alpha- and beta s-globin genes, we have obtained three transgenic mice with HbS levels ranging from 10 to 80% of total haemoglobin in their red cells. As observed in homozygous and heterozygous Hbs patients, the erythrocytes of this mouse sickle readily on deoxygenation. Irreversibly sickled cells, which are characteristic of sickle-cell patients homozygous for beta s, are also observed in the peripheral blood of the mouse with high levels of HbS.

Published
1990

123. Glucose 6‐phosphate dehydrogenase deficiency and red cell membrane defects: additive or synergistic interaction in producing chronic haemolytic anaemia

Author

Alfinito, F., primary, Calabro, V., additional, Cappellini, M. D., additional, Fiorelli, G., additional, Filosa, S., additional, Iolascon, A., additional, Giudice, E. Miraglia del, additional, Perrotta, S., additional, Migliorati, R., additional, Vallone, D., additional, Rotoli, B., additional, and Luzzatto, L., additional

Published
1994
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141. Book reviews.

Author

Jordan VC, Luzzatto L, and Eibl MM

Published
2007

147. Red cell glucose-6-phosphate dehydrogenase status and pyruvate kinase activity in a Nigerian population.

Author

May, Jürgen, Meyer, Christian G., Großterlinden, Lars, Ademowo, Olusegun G., Mockenhaupt, Frank P., Olumese, Peter E., Falusi, Adeyinka G., Luzzatto, Lucio, Bienzle, Ulrich, May, J, Meyer, C G, Grossterlinden, L, Ademowo, O G, Mockenhaupt, F P, Olumese, P E, Falusi, A G, Luzzatto, L, and Bienzle, U

Subjects
GLUCOSE-6-phosphate dehydrogenase deficiency, PYRUVATE kinase, ERYTHROCYTES, BLOOD testing
Abstract

Glucose-6-phosphate dehydrogenase A- (G6PD A-) deficiency is a common enzymopathy in Africa that sporadically leads to manifest haemolytic anaemia. It is not exactly known how far the haematological status of individuals with either homozygous or heterozygous G6PD A- deficiency differs from that of individuals with normal G6PD activity. In a field study in Nigeria, we determined G6PD gene variants, the corresponding G6PD and pyruvate kinase (PK) activities, and basic haematological parameters in clinically healthy individuals, who were, in part, asymptomatically infected by malaria parasites. Red blood cell counts and haemoglobin levels were lower in G6PD A- deficient than in G6PD normal subjects. PK activities were higher in G6PD deficients, indicating a younger red cell population in these individuals. These findings suggest that G6PD A- deficiency is accompanied by chronic subclinical haemolysis. As a consequence, the reduced life span of red cells leads to an impaired diagnosis of G6PD heterozygosity when applying routine biochemical methods. [ABSTRACT FROM AUTHOR]

Published
2000
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