PubMed Health⌕ Search

Biomedical subjects

U Carpentieri

Publications and source records attributed to U Carpentieri.

At least 19 recordsLinked to original sources
PubMed1991

Growth, ribonucleotide reductase and metals in murine leukemic lymphocytes.

Trace metals are essential for the growth and several other properties of human lymphocytes. We studied the effects of media with variable concentrations of three metals (Fe2+, Cu2+, Zn2+), a metal chelator (deferoxamine, DFX) and a cell-growth inhibitor (hydroxyurea) on the growth, intracellular metal concentration and activity of the enzyme ribonucleotide reductase in murine leukemic lymphocytes (L1210). Intracellular concentrations of Fe and Cu fluctuated within narrow limits in normal media, but decreased to very low concentrations in metal-poor media. The intracellular Zn concentration did not vary appreciably. Growth in intact cells decreased by 50%-70% when normal media were replaced by metal-poor media, but returned to control values when media were supplemented with gradually increasing concentrations of Fe and Cu. Fe and Cu had synergistic effects, while Zn had no stimulatory action. Hydroxyurea and DFX both inhibited cell growth, but only DFX inhibition was reversed by addition of metals. The addition of the above metals and inhibitors to the cell extracts produced effects on ribonucleotide reductase activity similar to those observed on the growth of whole cell preparations (stimulation by Fe and Cu, inhibition by Zn, DFX and hydroxyurea). These findings show that (a) the intracellular metal concentration is maintained in a narrow range during cell growth; (b) ribonucleotide reductase activity varies with cell growth; (c) ribonucleotide reductase activity and cell growth increase with Fe and Cu and decrease with Zn and DFX. Our data suggest that (a) Fe, Cu and Zn may have some effect on the growth and ribonucleotide reductase activity of L1210 cells, that (b) Fe, Cu and Zn may operate in a related and interdependent way and that (c) DFX inhibits cell growth probably through inhibition of the reductase activity and chelation of the Fe of its Fe-containing subunit. We conclude that any study on one of these metals should always include the other two and that manipulation of intracellular metals should be investigated as a potential therapeutic modulator of growth in leukemic lymphocytes.

Animals↗
PubMed1988

Effects of iron, copper, zinc, calcium, and magnesium on human lymphocytes in culture.

The effects of simultaneous changes of calcium, magnesium, iron, copper, and zinc concentrations were evaluated in normal human T and B lymphocytes, cultured in cation-depleted media. Optimal concentrations for thymidine incorporation (TI) in both cell populations were Fe and Zn 15 microM and Cu 5 microM; for T cells Ca 2 mM and Mg 4 mM; for B cells Ca 4 mM and Mg 6 mM. TI decreased with increasing molarity of cations and the decrease was particularly apparent with Cu. Minimal amounts of Ca and Mg (0.5 mM) were necessary for growth, even in presence of optimal concentrations of Fe, Cu, and Zn. Fe and Cu showed synergistic stimulatory effects at low concentrations and synergistic inhibitory effects at high concentrations. Antagonism between Fe and Zn, Cu and Zn, and Ca and Zn was also demonstrated. CD4/CD8 increased with PHA stimulation in presence of Zn, and decreased with ConA stimulation in presence of Zn or Fe. The results demonstrate: (1) the relationship and interdependence of Fe, Cu, and Zn concentrations in modulating the growth of normal lymphocytes; (2) the stimulatory effects of Fe on B cells and Zn on CD8 positive cells; (3) the inhibitory effect of Cu at concentrations lower than those of Fe and Zn; (4) the requirement of Ca and Mg in certain concentration and ratio for the action of the other cations; and (5) the Ca and Mg requirement for the growth of B cells higher than T cells.

B-Lymphocytes↗
PubMed1987

Observations on the use of a cation exchange resin for the preparation of metal-depleted media for lymphocyte culture.

A chelating resin specific for divalent cations (Chelex) was used to prepare metal-depleted media for lymphocyte culture. A batch procedure (resin in pH 7.4 phosphate buffer/specimen, 1:1) removed 70-80% of iron, 77-87% of copper and 88-98% of zinc, calcium and magnesium. At variance with other reports, when a resin/specimen ratio of 1:4 was used, iron chelation decreased to 40%, whereas other cation chelation remained unchanged. Best chelation for iron and calcium was obtained at pH 5-6.4; for copper, zinc and magnesium, at pH 7.4-8.0. During the procedure protein content decreased by 8-10%; arginine and lysine by 80%; asparagine, cystine, tyrosine and phenylalanine by 60%, other amino acids by 35%. These new data suggest that cation-depleted media prepared with Chelex may be used to study the effects of cations on lymphocytes in culture, provided that the most appropriate pH and resin/specimen ratio are selected and adequate amino acid replacement is performed. Results on normal human lymphocytes are reported.

Cation Exchange Resins↗
PubMed1986

Copper, zinc, and iron in normal and leukemic lymphocytes from children.

Copper, zinc, and iron were quantitated in the serum and lymphoid cells of the peripheral blood of healthy children and children with acute lymphocytic leukemia. Copper and iron concentrations in serum and cells were significantly higher and zinc concentration in the cells significantly lower in leukemic patients than in healthy donors, whereas the increase of zinc in the serum was not significant. The concentration of all minerals was higher in T-cell enriched preparations. There was a significant correlation between copper and iron and between copper and zinc, but not between iron and zinc in normal and leukemic lymphocytes. No correlation was demonstrated among the three minerals in the serum. There were no significant differences associated with ethnicity, age, sex, type of leukemia, or number of leukemic cells. However, a group of five children with non-B-, non-T-cell acute lymphocytic leukemia, nonreactive skin tests, and low serum immunoglobulins had high concentrations of copper and iron and low concentration of zinc in their leukemic cells. Since copper, zinc, and iron are associated with lymphocyte maturation and regulation of immune function, these new data will provide a tool for the study of the relationship between changes in concentrations of these metals and the modification of the immune response often present in hematologic cancers.

Child↗
PubMed1985

Leukemia with a novel 4q11q rearrangement.

Translocation (4;11)(q21;q23) is characteristic of a distinct acute leukemic syndrome. We report an 8-wk-old male patient with the clinical features ascribed to t(4;11), but with an unusual chromosome rearrangement consisting of an insertion of the 11q23 band into the q21 region of chromosome #4.

Chromosomes, Human, 4-5↗
PubMed1985

Zinc deficiency and blood lymphocyte function with sickle cell disease.

A relationship between zinc deficiency and lymphocyte function in children with sickle cell disease (SCD) has been suggested. Number and function of B and T lymphocytes were assessed in 3 matched groups of children: normal subjects with Hb A and normal zinc; patients with SCD; and normal zinc (SCD-N); and patients with SCD and decreased zinc (SCD-D). Percentages of B and T cells, response to cutaneous antigens and increases in tetanus antibody titres were similar among all groups. Absolute numbers of WBC, lymphocytes and B and T cells were markedly increased in SCD-N (p less than 0.001) and to a lesser degree in SCD-D (p less than 0.01). Controls and SCD-N had a normal response to all mitogens, which was not inhibited by SCD-D sera. SCD-D had a depressed response to PHA (p less than 0.001), which was not corrected by zinc addition in vitro. These findings indicate that B cell function and T cell-dependent delayed hypersensitivity are normal in children with SCD and are independent of body zinc status. They also suggest some abnormality of T helper cells in the presence of zinc deficiency, and in the absence of a demonstrable serum inhibitor.

Adolescent↗
PubMed1983

Neutrophils and zinc in infection-prone children with sickle cell disease.

Neutrophils can be distinguished as EA negative (EA-N) or EA positive (EA+N), according to rosette formation with sheep erythrocytes. EA- neutrophils show a bactericidal activity 50% to 70% lower than EA+ neutrophils. Thirty children with sickle cell disease were studied during steady state and crises/infections, together with matched control children. EA+ and EA- neutrophils, zinc levels in the body, and frequency of previous bacterial infection were evaluated. Sixty percent of the patients (18/30) had zinc deficiency (zinc less than 8.5 micrograms/10(10) RBC): of this group, more than three fourths (14/18) had a high frequency of infections (greater than or equal to 3/yr) and most of those (11/14) also had an increased percentage of EA- neutrophils (80% to 85% v 35% to 45% in control subjects). Only 4/18 of patients with zinc deficiency had a low frequency of infections, and only one of these four had a higher percentage of EA- neutrophils. In patients with normal zinc levels (12/30 or 40%), only three had frequent infections, but only one of these had an increased percentage of EA- neutrophils. The number of EA+ neutrophils increased after stimulation with epinephrine or during crises/infections. In six patients with more pronounced zinc deficiency and more severe crisis/infection, a delay in the increase of EA+ neutrophils occurred and was corrected by treatment. These findings suggest that a higher percentage of neutrophils with less bactericidal activity in many children with sickle cell disease and zinc deficiency may be a factor in the higher incidence of infections noted in these patients, and zinc might play a role in the formation, release, and activity of neutrophils.

Adolescent↗
PubMed1981

Adenylate cyclase and guanylate cyclase activity in normal and leukemic human lymphocytes.

Adenylate cyclase (AC) and guanylate cyclase (GC) activities were studied in normal B-enriched and T-enriched lymphocytes, in lymphocytes of children with acute lymphocytic leukemia (ALL), and in lymphocytes of adults with chronic lymphocytic leukemia (CLL). AC activity was greater in normal B than T lymphocytes (215 pmole/min/mg protein versus 80 pmole in the membrane-enriched fraction) and i both increased greatly after stimulation with isoproterenol and more so with prostaglandins E and F2 alpha. In leukemic lymphocytes, AC showed depressed activity (20 pmole in ALL cells and 55 pmole in CLL cells) and was less sensitive to hormonal stimulation: this loss of sensitivity occurred to a greater extent in ALL than in CLL lymphocytes. GC activity was greater in normal T than B cells (in membrane-enriched fraction: 10.2 pmole versus 5.3 pmole). It increased little with isoproterenol and prostaglandins stimulation, and much more with sodium azide and dehydroascorbic acid stimulation. GC activity was increased in both types of leukemic lymphocytes (23 pmole for ALL cells and 18 pmole for CLL cells) and was insensitive to stimulation. Possible derangement of cyclase and cyclic nucleotide regulation in leukemic cells is suggested.

Adenylyl Cyclases↗