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Biomedical subjects

G F Gaetani

Publications and source records attributed to G F Gaetani.

At least 55 records · Page 3Linked to original sources
PubMed1984

Clonal origin of cells restricted to monocytic differentiation in acute nonlymphocytic leukemia.

Two patients with acute monocytic leukemia and heterozygous for the Mediterranean variant of the X-linked enzyme, glucose-6-phosphate dehydrogenase (G6PD), were investigated to determine the number and type of progenitor cells involved. Mosaicism for Mediterranean G6PD was assessed by the different rate of utilization of 2-deoxy glucose-6-phosphate (2dG6P) by normal and Mediterranean variants of G6PD. The monocytoid blasts were found to express one type of G6PD only, indicating their clonal origin from a common progenitor cell, whereas all other hemopoietic cell populations tested expressed the heterozygous phenotype. The finding of a unique involvement of the monocytic line in two cases of acute nonlymphocytic leukemia (ANLL) represents further evidence of heterogeneity of stem cell involvement in ANLL.

Cell Differentiation↗
PubMed1983

Reexpression of normal stem cells in erythroleukemia during remission.

A patient with erythroleukemia and heterozygous for the Mediterranean variant of the X-linked enzyme glucose-6-phosphate dehydrogenase (G6PD) was studied to determine the number and type of progenitor cells in which the disease arose. G6PD mosaicism was assessed by the different rate of utilization of 2-deoxy-glucose-6-phosphate (2dG6P) by normal and Mediterranean variants of G6PD. Erythroleukemia is established as a clonal disease involving a precursor cell common to the erythroid and myeloid lines. After intensive chemotherapy, restoration of nonmonoclonal hemopoiesis is achieved, as indicated by the reappearance of the mosaic phenotype in hemopoietic cell populations.

Aged↗
PubMed1982

Primary thrombocythemia: clonal origin of platelets, erythrocytes, and granulocytes in a GdB/GdMediterranean subject.

A patient with primary thrombocythemia, who was heterozygous for glucose-6-phosphate dehydrogenase deficiency (GdB/GdMed), was investigated to test for the clonal origin of this myeloproliferative disorder. In order to assess somatic cell mosaicism in various tissues, we have made use of the different rate of utilization of 2-deoxyglucose-6-phosphate, an analog of glucose-6-phosphate, by normal glucose-6-phosphate dehydrogenase and by the Mediterranean variant: the results demonstrate that essential thrombocythemia is a clonal disease involving the erythrocytic, granulocytic, and megakaryocytic series, without affecting monocytes, T lymphocytes, and non-T lymphocytes.

Aged↗
PubMed1981

G6PD Napoli and Ferrara II: two new glucose-6-phosphate dehydrogenase variants having similar characteristics but different intracellular lability and specific activity.

Two new glucose-6-phosphate dehydrogenase (G6PD, D-glucose 6-phosphate: NADP oxido reductase, E.C. 1.1.1.49) variants, designated G6PD Napoli and G6PD Ferrara II, are described in propositi from two unrelated families. Characterization side by side of the two variants according to W.H.O. recommendations reveals minor differences which are mostly related to utilization of artificial substrates (increased in both cases as compared with normal G6PD type B). Other properties, which are not significantly distinctive between the two variants, are an enzyme activity amounting to nearly 20% of normal, a decreased electrophoretic mobility, decreased Km values for glucose-6-phosphate and NADP, normal thermostability and biphasic pH curves. However, marked differences emerged between the two variants and between either variant and G6PD B as well, when a number of microtechniques were used. These were: (1) the half-lives of G6PD Napoli and G6PD Ferrara II are 16 and 29 d, respectively, while that of G6PD B is 63 d; (2) the specific activities, measured by a method involving direct estimation of G6PD protein on sodium dodecyl sulphate polyacrylamide gel electrophoretic tracings, are 166 I.U./mg (G6PD Napoli) and 59 I.U./mg (G6PD Ferrara II), as compared with normal value of 180 I.U./mg (G6PD B). On the whole, these findings allow the conclusion that the deficiency of catalytic activity is related to an accelerated though distinctive decay of both mutant enzyme proteins within the affected erythrocytes and that a significant impairment of catalytic efficiency is also involved, as a result of the underlying structural mutation in the case of G6PD Ferrara II.

Adult↗
PubMed1981

2-deoxy-glucose-6-phosphate utilization in the study of glucose-6-phosphate dehydrogenase mosaicism.

The electrophoretic difference between normal glucose-6-phosphate dehydrogenase (G6PD) and two common variants (G6PD A and G6PD A-) has made the G6PD enzyme system very useful for genetic studies and for investigation on the clonal origin of tumors. This approach has not been possible for another common variant, G6PD mediterranean, which has a normal electrophoretic pattern. The different utilization of 2-deoxy-glucose-6-phosphate (2dG6P), an analog of the normal substrate, by the normal enzyme and the Mediterranean variant, allows a convenient determination of the degree of mosaicism in mononuclear cells from heterozygotes.

Deoxyglucose↗
PubMed1981

Effect of divicine and isouramil on red cell metabolism in normal and G6PD-deficient (Mediterranean variant) subjects. Possible role in the genesis of favism.

Fava beans contain high amounts (up to 6.7 g/100 g dry weight) vicine and convicine. Their active aglycones divicine and isouramil have equivalent metabolic effects. They rapidly oxidize GSH to GSSG in normal and G6PD-deficient red cells. No regeneration of GSH occurs in deficient cells. The stoichiometry of the divicine oxidation of GSH is 1:1. Ascorbic acid is quickly oxidized by isouramil in both normal and deficient cells but regenerates only in normal cells. Isouramil oxidizes NADH at a much lesser extent than NADPH. Glycolysis is activated at the glyceraldehyde 3-phosphate dehydrogenase step. Divicine strongly stimulates hexone monophosphate shunt only in normal red cells. Divicine alone or associated with ascorbic acid has almost no effect in deficient red cells. Malonyl dialdehyde production is slight and virtually the same in normal and deficient cells treated with 5 mM isouramil. Large polypeptide aggregates are formed after 12 and 24 hours incubation with 1 mM divicine in deficient cells only. Divicine (0.25 mM) markedly decreases the filterability of deficient cells. The results are consistent with a causal role of divicine/isouramil in the genesis of the hemolytic crisis occurring in G6PD-deficient subjects after fava bean ingestion.

Ascorbic Acid↗
PubMed1979

Favism: erythrocyte metabolism during haemolysis and reticulocytosis.

The reduced activity of glucose-6-phosphate dehydrogenase (D-glucose-6-phosphate; NADP+ 1-oxidoreductase; G6PF) in Mediterranean erythrocytes explains the precarious equilibrium of the hexose monophosphate pathway (HMP) and the susceptibility of these cells to haemolytic agents. G6PD-deficient erythrocytes, in steady-state conditions, have a low NADPH/NADP+ ratio, thus allowing the HMP to operate at its maximal intracellular rate and to compensate the intrinsic erythrocyte enzyme deficiency. Studies started soon after accidental intake of fava beans by sensitive G6PD-deficient subjects demonstrate a decrease of both NADPH/NADP+ ratio and reduced glutathione. The metabolic effects induced by fava beans may be attributed to oxidative stress probably associated with an inhibitor effect of some unknown metabolite on the HMP. The availability of erythrocytes from subjects recovering from haemolysis with high reticulocyte counts and increased G6PD activity, provides new information on the rate of synthesis as well as on the in vivo decay of the mutant enzyme. Correlation of G6PD activity to reticulocyte count and extrapolation to an ideally homogenous population of reticulocytes reveal that the mutant enzyme is synthesized at a nearly normal rate. Furthermore, the present correlation allows an estimate of the in vivo half-life of Mediterranean G6PD. The rate of decline of about 8 d observed in this study well correlates to the intracellular metabolic aspects of G6PD Mediterranean erythrocytes.

Adolescent↗
PubMed1979

Serum lactic dehydrogenase as a prognostic tool for non-Hodgkin lymphomas.

Serum LDH levels have been found to be significantly increased in non-Hodgkin lymphoma (NHL) patients, both histiocytic and lymphocytic. The duration of survival of NHL negatively correlates with the level of serum lactic dehydrogenase (LDH), and statistical analysis reveals that patients with lower levels of LDH have a longer survival rate than the patients with higher LDH activity, irrespective of their histologic classification. The analysis of the results by the Test for Trend in Prognosis allows us to establish that the correlation of the rate of survival and LDH levels is independent from other clinical parameters.

Humans↗
PubMed1978

Effect of haemolysis on the hexose monophosphate pathway in normal and in glucose-6-phosphate dehydrogenase-deficient erythrocytes.

The hexose monophosphate pathway of human glucose-6-phosphate dehydrogenase (EC 1.1.1.49) - deficient erythrocytes is under a severe and unexplained restraint (Gaetani, G.D., Parker, J.C. and Kirkman, H.N. (1974) Proc. Natl. Acad. Sci. U.S. 71, 3584-3587). In this study the hexose monophosphate pathway activity and the NADPH level of normal and glucose-6-phosphate dehydrogenase-deficient erythrocytes were measured soon after haemolysis. The results indicate a prompt increase in 14CO2 evolution and a rise in MADPH levels. Since, in this study, the concentration of the haemolysate is comparable to that of intact erythrocytes, the relief of the restraint on glucose-6-phosphate dehydrogenase through dilution-dependent dissociation from inactivator or inhibitor is excluded. The possibility that the intracellular restraint may result from compartmentalization of glucose-6-phosphate dehydrogenase and substrates or from properties of the intact membrane of the erythrocytes is suggested.

Carbon Dioxide↗
PubMed1978

Biochemical mechanisms of glucose-6-phosphate dehydrogenase deficiency.

A solid-phase radioimmunoassay for human glucose-6-phosphate dehydrogenase (D-glucose-6-phosphate: NADP+ 1-oxidoreductase; EC 1.1.1.49) was developed that allowed the specific activity of this enzyme protein to be measured in lysates from whole erythrocyte populations, in lysates from erythrocytes of different ages, and in purified samples. The enzyme was highly purified from erythrocytes of single donors by a simple procedure of affinity chromatography with insolubilized adenosine 2',5'-bisphosphate. These techniques were used in an attempt to elucidate the molecular mechanisms leading to deficiency of glucose-6-phosphate dehydrogenase activity in two genetic variants of the enzyme, i.e., the Mediterranean and the Seattle-like variants. The results indicate that the lowered activity of erythrocytes containing the Mediterranean variant of glucose-6-phosphate dehydrogenase is related to an enhanced rate of degradation of a catalytically defective protein synthesized at a nearly normal rate. Synthesis of a normally functioning protein and an increased breakdown of it are involved in the Seattle-like variant of the enzyme.

Cross Reactions↗
PubMed1976

NADP+ and NADPH in glucose-6-phosphate dehydrogenase-deficient erythrocytes under oxidative stimulation.

A mild oxidative stimulation of the hexose monophosphate pathway of human glucose-6-phosphate dehydrogenase (EC 1.1.1.49)-deficient erythrocytes (Mediterranean variant) causes a significant drop in NADPH. These results, other than to confirm that glucose-6-phosphate dehydrogenase deficiency is a product deficiency disorder, demonstrate that under oxidative stimulation glutathione reductase may become functionally impaired and GSSG cannot be reduced at a sufficient rate.

Erythrocytes↗
PubMedDate not supplied

Feprazone: absence of hemolytic effects in glucose-6-phosphate dehydrogenase-deficient subjects.

Some drugs, including nonsteroidal antiinflammatory compounds, can be hemolytic in glucose-6-phosphate dehydrogenase-deficient patients. We have studied the potential hemolytic activity of feprazone, a nonsteroidal antiinflammatory compound in vitro and in vivo. Agents that may be hemolytic for glucose-6-phosphate dehydrogenase-deficient erythrocytes will stimulate the hexose monophosphate shunt in normal erythrocytes. Eleven normal subjects were treated with feprazone and their erythrocytes were incubated in their own sera (containing active feprazone metabolites) and [1-14C]-glucose. Because no statistically significant increase in 14CO2 evolution was observed, 15 pediatric male patients with glucose-6-phosphate dehydrogenase deficiency who required antiinflammatory treatment were treated with feprazone. No hemolytic crises and no statistically significant changes of hematologic tests were observed.

Adolescent↗