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Biomedical subjects

L Luzzatto

Publications and source records attributed to L Luzzatto.

At least 199 records · Page 11Linked to original sources
PubMed1982

Decreased number of circulating BFU-Es in paroxysmal nocturnal hemoglobinuria.

In order to quantitate early erythroid progenitor cells in paroxysmal nocturnal hemoglobinuria (PNH), we have cultured peripheral blood mononuclear cells from 7 PNH patients in a 0.8% methylcellulose medium containing erythropoietin, 2 U/ml. In our experimental conditions, the number of erythroid colonies obtained per 5 X 10(5) mononuclear cells plated was 20.1 +/- 1.9 (SEM) in normal subjects and 2.8 +/- 0.56 (SEM) in PNH patients. In plates from PNH subjects, 38 of 117 showed no growth of erythroid colonies, whereas plates from normal subjects always had colonies. Our findings suggest that PNH patients, despite their hemolytic condition, have a depleted erythroid precursor compartment, and this may play a major role in the pathogenesis of their anemia.

Adult↗
PubMed1982

The pattern of thalassemia in Naples.

1. The expected number of patients with Cooley anemia in Naples, as predicted from heterozygote frequencies, is about 300 which is more than that found from hospital statistics. 2. Considering the presence of at least two beta-thalassemic alleles and the coexistence of a significant incidence of the Lepore gene in the population of the area surrounding Naples (the maximum incidence is thought to be in the neighboring province of Caserta), there are at least 6 different genotypes (3 true homozygotes and 3 genetic compounds) that can give rise to clinically important thalassemia syndromes, ranging from thalassemia intermedia to classic Cooley anemia. 3. Since an alpha-thalassemic gene is also present at polymorphic frequency in this population, this gene may coexist by random assortment in subjects who also have a beta-thalassemia syndrome, thus accounting for part of the variability of globin gene expression. 4. It is remarkable that 2 brothers homozygous for Hb Lepore present differences in the non-alpha/alpha ratio. The clinical differences could be explained by the gamma/alpha mRNA ratio close to 1 in one of them.

Child↗
PubMed1981

Plasmodium falciparum malaria and human red cells. II. Red cell genetic traits and resistance against malaria.

In 702 Nigerian children under 6 years of age the incidence and the severity of malarial infection was studied with respect to haemoglobin types and red cell glucose-6-phosphate dehydrogenase variants. The results suggest that Hb AS as well as the female genotype GdA-/GdB offer selective advantage against the disease. Parasite densities in carriers of these genotypes were significantly lower than in other subjects. Whereas protection by Hb AS was found mainly in children between 2 and 4 years of age, the advantage afforded by GdA-/GdB was similar in all age groups. Possible mechanisms are discussed.

Child↗
PubMed1981

Plasmodium falciparum malaria and human red cells. I. A genetic and clinical study in children.

In a holoendemic malaria region of Nigeria children of both sexes aged from 9 months to 6 years with an acute febrile illness were examined for malaria. In 461 children with malaria, predominantly P. falciparum, and in 241 children without malaria, haemoglobin levels, haemoglobin types, red cell glucose-6-phosphate dehydrogenase variants and parasite densities were recorded. The G6PD status was determined by a combination of spectrophotometric enzyme quantitation, electrophoresis and the cytochemical methaemoglobin elution technique. Malaria morbidity and parasitaemia decreased with increasing age. Frequencies of haemoglobin types and G6PD variants were not significantly different in the malaria and the non-malaria series. Haemoglobin values were significantly lower in children with malaria to about the same extent in HbAA and HbAS subjects, but no close correlation existed between haemoglobin level and parasite density. Details of the G6PD classification and the effect of malaria on enzyme activity are discussed.

Age Factors↗
PubMed1981

New genetic variants of glucose 6-phosphate dehydrogenase (G6PD) in Italy.

Six new variants of human erythrocyte G6PD have been characterized. All of them were found in Italian males and all were associated with enzyme deficiency, but only two with signs of haemolysis. These and other variants reported in the literature, which must thus far be regarded as sporadic, are found to map in parts of Italy where common types of G6PD deficiency are also prevalent.

Adolescent↗
PubMed1980

Genetic heterogeneity of glucose 6-phosphate dehydrogenase deficiency in Sardinia.

Glucose 6-phosphate dehydrogenase (G6PD) activity was assayed quantitatively in red cells from 100 consecutive G6PD-deficient newborn male babies born in a city hospital in Sassari, Sardinia. In four cases G6PD activity was between 30% and 45% of normal: these appeared on electrophoresis to be identical with G6PD Seattle-like. In 65 cases G6PD activity ranged from 2% to 14% of normal, while in the remaining 31 samples no activity could be detected in crude hemolysates. G6PD was partiall purified from 39 samples having activity below 14% of normal (including 20 with zero activity). G6PD activity could now be determined in all, and it was fully characterized in nine samples. These were shown to belong to two distinct classes on grounds of the Michaelis constant for glucose 6-phosphate and the elution profile from DEAE-Sephadex columns. These properties were compared with those of G6PD-deficient samples from Greece and from Israel. We conclude that there are at least three polymorphic G6PD-deficient variants in Northern Sardinia: G6PD Seattle-like, G6PD Mediterranean, and a new variant, which we designate G6PD Sassari. The GdMediterranean and GdSassari genes have been shown to breed true in family studies. We also produce evidence that the definition of G6PD Mediterranean must be carefully reassessed.

Genes↗
PubMed1980

Genetic and biochemical heterogeneity of beta-thalassaemia in Naples.

We have investigated 32 children with Cooley's anaemia from Naples, Italy. Criteria for inclusion in the study were: (a) typical clinical and haematological findings; (b) absolute transfusion requirement; and (c) elevated Hb A2 in both parents. From biosynthetic studies we have established that five children (including two sets of sibs) had beta-0 thalassaemia, while the rest had beta + thalassaemia. Thus, the frequency of beta + thalassaemia among unrelated patients was about 90%. The distribution of beta/alpha ratios among beta + patients ranged from 0.01 to 0.16 and it was bimodal, consistent with some of them having a beta-0/beta + genotype and others a beta +/beta + genotype. The distribution of beta/alpha ratios of the patients' parents (obligate heterozygotes) ranged from 0.24 to 0.73, and it was plurimodal, consistent with the coexistence in this population of multiple beta thalassaemia alleles, of which one must be beta-0 and at least one is beta +. A systematic analysis of 20 families indicates that the beta/alpha ratio is to some extent quantitatively inherited, and its suggests non-randomness in the assortment of beta thalassaemia alleles that can give rise to a Cooley's phenotype.

Adolescent↗
PubMed1980

New clinical and biochemical findings from 235 patients with hemoglobin Lepore.

The study of 76 Leporian families with 214 heterozygous, 9 homozygous, and 12 combinations with different type of thalassemia has allowed the authors to discuss three points: (1) The homozygous condition for Hb Lepore was until now found only in 19 people worldwide. The affirmation that this state is always similar to classic Cooley's anemia cannot be confirmed by us because the majority of our patients did not have a very severe anemia and they are still alive and in a fairly good condition. Splenectomy is always useful. In two of our patients it was found that the ratios between delta + beta and alpha mRNA agreed well with the delta beta/alpha chain biosynthetic ratio. (2) Two new forms of combined Leporian conditions were investigated. These are the combinations of Hb Lepore with delta beta thalassemia and a variant of beta thalassemia, namely, the isolated-high-Hb-A2 beta thalassemia. Both diseases present the same Hb pattern as that of homozygous Hb Lepore. Both presented a mild course also. (3) The multiform and very large experience (more than 5000 cases of genotypical hemoglobinopathies observed in the last 20 years) led us to observe that in carriers of Hb Lepore there was frequently the concomitance of malignancies, especially hemolymphoblastoses. In fact, the risk of such malignancies in the Hb Lepore carriers is 10 times higher than for thalassemics. The explanation of this finding is uncertain. It is possible, however, that the peculiar abnormality of Hb Lepore may be related to malignancy.

Adult↗
PubMed1980

Coexistence of three hemoglobins with different alpha-chains in two unrelated children (with family studies indicating polymorphism in the number of alpha-globin genes in the Sardinian population).

In each of two families from Sardinia, Italy, we have found segregation for two alpha-chain hemoglobin variants, which we have identified as G Philadelphia [alpha 68 (E17) Asn leads to Lys] and J Sardinia [alpha 50 (CE8) His leads to Asp], respectively. One family also shows segregation for the beta-thalassemia trait. One subject in one family and two subjects in the other family have in their red cells both hemoglobin variants, G and J, in addition to HbA. One of the subjects, a newborn baby, has six major hemoglobin components; alpha 2A beta 2, alpha 2A gamma 2, alpha 2G beta 2, alpha 2G gamma 2, alpha 2J beta 2, alpha 2J gamma 2. These three cases are to be added to three previous cases in the literature in whom three different alpha-chains have been found in the same blood. These findings prove that the alpha-chain locus is duplicated in the Sardinian population, as it is in other populations. The relative amounts of the various hemoglobin species found in members of our two families, through three and four generations respectively, suggest that chromosomes with and without duplication may coexist in the same population.

Blood Protein Electrophoresis↗
PubMed1979

Imbalance in X-chromosome expression: evidence for a human X-linked gene affecting growth of hemopoietic cells.

In each of six family members who were heterozygous at the X-linked locus for glucose-6-phosphate dehydrogenase, only one or the other of the two alleles at that locus was almost exclusively expressed. The data are consistent with evidence that X-chromosome inactivation is a random process that may be followed by selection for one of the two resulting cell types on the basis of an unknown gene, which is located on the X chromosome and which can affect the rate of proliferation of hemopoietic cells in humans.

Alleles↗
PubMed1979

Genetic heterogeneity of "normal" human erythrocyte glucose-6-phosphate dehydrogenase: an isoelectrophoretic polymorphism.

Quantitative determination of glucose-6-phosphate dehydrogenase (G6PD; D-glucose-6-phosphate: NADP+ 1-oxidoreductase, EC 1.1.1.49) activity was carried out in 214 male Nigerian children of 84 mothers with known Gd genotype. The relative intrasibship difference in G6PD activity (normalized to the lowest value within the sibship) was below 0.18 in all cases but one when the children were known to have the same Gd+ allele (identical by descent); whereas it was higher than 0.18 in 18 out of 33 sibships in which children might have had either of the two maternal (electrophoretically identical) Gd+ alleles. G6PD from 10 (8 G6PD B and 2 G6PD A) children belonging to four of the sibships possessing high quantitative variation in G6PD activity was partially purified and extensively characterized. The 8 G6PD type B samples fell unambiguously into two classes on the basis of Km values for glucose 6-phosphate (determined at variuos pH values), and KCl gradient elution from DEAE-Sephadex columns. The two types of G6PD B were resolved from an artificial mixture on a DEAE-Sephacel column. The two G6PD type A samples were also different from each other by the same criteria. We conclude that "normal" G6PD is genetically heterogeneous and that the structural Gd alleles concerned are all polymorphic in the Nigerian population. In this instance, a human enzyme polymorphism, not associated with enzyme deficiency, is revealed by an approach other than electrophoresis.

Alleles↗