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Biomedical subjects

L Luzzatto

Publications and source records attributed to L Luzzatto.

At least 217 records · Page 12Linked to original sources
PubMed1979

Defects in DNA and globin messenger RNA in homozygotes for hemoglobin Lepore.

Globin messenger RNA (mRNA) isolated from three patients homozygous for hemoglobin Lepore is shown to have a marked reduction of the amount of beta-like globin mRNA (Lepore-globin mRNA sequences) compared with alpha-globin mRNA by molecular hybridization. The relative amounts of alpha- and Lepore mRNA are similar to the amounts of alpha- and Lepore globin synthesized in intact cells and by isolated mRNA in a cell-free system. It is also demonstrated that Lepore-globin mRNA can completely hybridize to full-length or nearly full-length beta-globin specific complementary DNA and protect it from nuclease digestion, indicating close homology between the delta-mRNA sequences present in Lepore mRNA and the beta-complementary-DNA probe. We have also quantitated the numbers of beta-like globin gene sequences in genomic Lepore DNA by molecular hybridization and demonstrated a reduction in their number consistent with the Lepore gene being a delta beta-gene fusion product.

Adolescent↗
PubMed1979

Genetically determined deficiency of glucose 6-phosphate dehydrogenase (type-A-) is expressed in the liver.

G6PD activity was determined in liver biopsy specimens from 31 patients (25 men and six women). The G6PD genotype of the patients was determined by carrying out on lysates of their red blood cells quantitative assays of the enzyme and starch-gel electrophoresis. In 21 subjects with normal G6PD activity in red cells, a relatively wide variation of G6PD activity was found in liver extracts. By contrast, in 10 subjects with G6PD deficiency, the activity of the enzyme in liver extracts was always low. The difference between the distribution of liver G6PD activity values of G6PD-normal and G6PD-deficient subjects was statistically significant (p less than 0.01). We conclude that G6PD deficiency of the African type is also expressed in the liver. These findings may have a bearing on hyperibilirubinemia, which cannot be entirely attributed to hemolysis, often encountered in G6PD-deficient patients.

Adolescent↗
PubMed1979

Malaria and erythrocyte glucose-6-phosphate dehydrogenase variants in West Africa.

In a clinical study, 702 Nigerian children aged 1-6 years were examined for malaria. Comparison of morbidity rates and parasitemia of patients with different glucose-6-phosphate dehydrogenase (G6PD) status provided evidence that in heterozygous females the gene for G6PD deficiency (GdA-/GdB) confers an advantage against malaria.

Child↗
PubMed1977

Genetic variants of human erythrocyte glucose 6-phosphate dehydrogenase: new variants in West Africa characterized by column chromatography.

Five electrophoretically slow-moving genetic variants of glucose 6-phosphate dehydrogenase are described: four are from Nigeria and one is from Togo. All variants have normal or moderately reduced activity, and they are not associated with adverse clinical or haematological manifestations. Three variants have been fully characterized and are different from all previously described ones. Two variants have been partially characterized and at least one of them is also probably new. The overall population incidence of sporadic variants of G6PD in the Nigerian population is 0-3%. In the course of this study a previously described ion-exchange chromatographic technique for the characterization of G6PD variants has been extensively evaluated. Data are given on ten different variants to demonstrate the high resolving power of this technique.

Chromatography, Ion Exchange↗
PubMed1977

Comparison of GdA and GdB activities in Nigerians. A study of the variation of the G6PD activity.

We report a comparison between G6PD enzyme activities in lysates from GdA and GdB Nigerian healthy males. We confirm the previously reported higher mean activity of G6PD B. An analysis of the enzyme activity variation has been performed: the relative amount of variation found to be associated with this polymorphism is about 8%. A comparison has been made with other genetic polymorphisms.

Child↗
PubMed1976

Genetic variants of human erythrocyte glucose-6-phosphate dehydrogenase. Kinetic and thermodynamic parameters of variants A, B, and A- in relation to quaternary structure.

The values of Vmax and Km for the three genetic variants A, B, and A- of erythrocyte glucose-6-phosphate dehydrogenase have been determined at 10 different pH values in the range from 5.5 to 9.5, and at four different temperatures in the range from 18.5-40.0 degrees. The log Vmax versus pH curve for each of the enzymes shows a monotonic increase between pH 5.5 and 7, and a plateau from pH 7.5 upwards. These curves, and their temperature dependence, are compatible with the presence of a single ionizable group which, in its conjugate acid form, renders the enzyme-substrate complex inactive. The pK of this group is 6.94 at 18.5 degrees, and its enthalpy of ionization is 7.0 kcal mol-1. The log Km versus pH curves show a broad plateau between pH 6.2 and 8.2, interrupted by a sharp minimum at pH 7.2 for variant B, while variants A and A- show sharp maxima at pH 7.2 and 7.45, respectively. It is proposed that this unusual behavior depends on the dissociation of the tetrameric enzyme to dimers in this pH region. Specifically, it is shown that a sharp maximum or minimum of Km can arise if cooperative uptake or release of protons is linked to dimer formation, and if the degree of cooperativity is different for the free enzyme compared to the enzyme-substrate complex. The pH dependence of the equilibrium between the tetrameric and the dimeric form of the enzyme has been determined by gel filtration for the same three genetic variants B, A, and A-. In agreement with previous ultracentrifugal data, the enzyme is a tetramer in acid solution and a dimer in alkaline solution. The pH at which half of the enzyme is in dimeric form, under our experimental conditions, is 7.15 +/- 0.05 for variants A and B, and 7.35 +/- 0.05 for variant A-. These pH values correspond closely, for all three variants, to the sharp extrema in the pH dependence of their Km values for glucose 6-phosphate. From the measured dissociation equilibria, it can be inferred that the tetramer-dimer transition entails cooperative release of protons. The degree of cooperativity estimated from these data agrees closely with the independent estimate based on the pH dependence of Km.

Erythrocytes↗
PubMed1976

Monoclonal gammopathy (Waldenström's macroglobulinaemia) producing specific red cell antibody.

Two cases of Waldenström's macroglobulinaemia have been seen at University College Hospital, Ibadan in the last four years, Case 1 was a 30-year-old soldier who presented with splenomegaly and anaemia, was treated with chlorambucil, and had a complete remission sustained for over two years. Case 2 was a 58-year-old retired civil servant who presented with very severe anaemia and also splenomegaly, and died within three weeks of admission. Both patients had most of the typical features of Waldenström's disease, including retinal changes and serum IgM levels of 4200 and 5500 mg/dl respectively. In both cases an atypical cold antibody was detected in the course of blood cross-matching procedures. In case 1, the antibody agglutinated all adult and cord red cells tested, including the patient's own cells, to a titre of 8000 and above at 4 degrees C. Suprisingly enough, when the patient went into remission and the serum IgM level had fallen to 400 mg/dl, this antibody was no longer detectable and has not reappeared two years later. In case 2, the antibody agglutinated all adult red cells tested to a titre of 2000 at 20 degrees C but not the patient's own red cells. Since cord cells were agglutinated only to a titre of 4 to 20 degrees C it was concluded that the patient had an alloantibody with I-specificity. Therefore in both these patients the monoclonal immunoglobulin produced by the neoplastic lymphoid cell clone had specific activity against red cell antigens.

Adolescent↗
PubMed1976

Erythrocyte enzymes in neonatal juandice.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a major cause of severe neonatal jaundice in Nigeria, but not all G6PD-deficient babies become jaundiced. Neonatal jaundice not attributable to G6PD deficiency nor to any other known aetiology is also common. In an effort to explain these two facts, we have measured the levels of the three enzymes G6PD, glutathione peroxidase (GSHPX), and glutathione reductase (GSSGR) in 38 jaundiced newborns, 26 control newborns, and 44 normal adults, all of them males. We could not yet prove an additive effect of GSSGR or GSHPX deficiency with G6PD deficiency in causing jaundice. There was no evidence that low levels of GSHPX per se are associated with jaundice. However, jaundiced newborns with normal G6PD had significantly lower levels of GSSGR than control newborns with normal G6PD. These data suggest that a relatively low activity of GSSGR, a riboflavin-dependent enzyme, may predispose the red cells to accelerated destruction in the neonatal period.

Adult↗
PubMed1975

Glucose 6-phosphate dehydrogenase deficiency and sickle cell anemia: frequency and features of the association in an African community.

The glucose 6-phosphate dehydrogenase (G6PD) genotype was determined in 100 male patients with homozygous sickle cell anemia (SS) by a combination of quantitative assay, cytochemical testing, and starch-gel electrophoresis. Of the 100 patients tested, 16 were found to be G6PD deficient (GdA-), AND 84 G6PD normal (22GsA and 62 GdB). This distribution of G6PD genotypes did not differ significantly from that observed in the general population. The level of G6PD activity in GdA- SS patients was nearly always higher than in G6PD-deficient subjects who did not have an associated hemolytic state, but it was nearly always lower than in G6PD-normal subjects. The clinical course of sickle cell disease, including the degree of anemia, was not milder in GdA- than in G6PD-normal patients but could not be proved to be significantly more severe. It was concluded that in this community the incidence of G6PD deficiency in sickle cell anemia was not greater than would be expected by chance, and there was no evidence that the coexistence of the GdA- gene in SS patients ameliorated their disease.

Adolescent↗
PubMed1974

Genetic factors in malaria.

Some of the available information on the genetics of Plasmodium is reviewed, and some of its peculiarities are emphasized. Genetic factors in the human host that may affect susceptibility to malaria are critically evaluated. Most of the studies thus far have been concerned with the genetics of host erythrocytes but there is recent evidence that genes affecting immune processes may also be involved. At least two genes affecting red cells confer relative resistance to P. falciparum: the autosomal gene for haemoglobin S (Hb S) and the sex-linked gene for the glucose-6-phosphate dehydrogenase (G6PD) variant known as A(-). Whereas malaria selection can be regarded as established for these genes, it still remains a hypothesis for some other polymorphic traits of red cells. Differential susceptibility to P. falciparum of red cells with different genotypes has been tested by in vitro cultures, in which the invasion of new cells and intracellular development of the parasite can be followed by parasite counts and by (14)C-isoleucine uptake. A model that relates genetic factors in Plasmodium and in man and that may account for certain features of host-parasite interactions is presented.

Animals↗