Biomedical subjects
Publications and source records attributed to U Carpentieri.
Liver span of normal infants and children 2 months to 5 years of age was found to be significantly correlated with body height, weight, surface area, and age. However, it was best correlated with body surface area, reflecting a constant relationship between body size and liver size. Assessment of liver span is a useful test for evaluation of a child with apparent liver enlargement.
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Nineteen cardiac patients were given warfarin sodium to prevent thrombosis and embolism. Empirical dosage resulted in long hospital stays to obtain a stable therapeutic prothrombin time. Using a dosage of 0 therefore 5-0 therefore 7 mg/kg, therapeutic levels were achieved in a much shorter time. When prothrombin time was excessive, it was successfully reduced with vitamin K or plasma. A haematoma in one case and haematuria in another were easily controlled. Warfarin sodium appears to be appropriate and effective for children requiring anticoagulants within the above dosage limits and with meticulous follow-up.
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Mitochondria were isolated from lymphoblasts grown for 5 days in cell culture. Measurement of mitochondrial respiratory activity revealed poor response to adenosine 5'-diphosphate with reduced nicotinamide adenine dinucleotide-linked substrates but well-coupled active respiration with succinate as substrate. These mitochondria also exhibited rapid initial rates of respiration-supported calcium uptake as measured by dual-beam spectrophotometry. H+/2e- and Ca2+/2e- ratios were in normal limits for the lymphoblast mitochondria during calcium uptake in the presence of phosphate. In the absence of phosphate no calcium uptake, H+ ejection, or stimulation of oxygen consumption was observed. However, the lack of discharge of the accumulated calcium from the lymphoblast mitochondria upon inhibition of respiration suggests possible different mechanisms of cation transport compared to mitochondria from normal, mammalian cell types. Electron microscopy of freshly prepared mitochondrial suspensions revealed preparations with intact outer membranes and abundant cristae and that were relatively free of other cellular structures. These studies demonstrate the feasibility of obtaining intact respiring mitochondria from cultured lymphoid cells and indicate that active ion transport in these mitochondria may be significantly different from "normal" cell mitochondria.
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Trace metals have a role in the activity of the enzyme ribonucleotide reductase (RR) which is essential for the synthesis of DNA and the growth of lymphocytes. Manipulation of the intracellular metals of leukemic cells has been proposed for the therapeutic control of cell growth. We studied the effects of prolonged metal deprivation (Fe, Cu, Zn) on cell growth and RR activity of murine leukemic lymphocytes in culture in metal-depleted media. Intracellular metals, cell growth and RR activity were decreased in related and interdependent ways. A metal-chelator (deferoxamine, DFX) had similar effect. In all cases these effects were reversible by metal supplementation. We conclude that it is possible to control RR activity and growth of leukemic cells in vitro by exposing them to a metal-poor environment (eg. through the action of a chelator). These effects are not permanent, but might be beneficial if integrated with more conventional measures (chemotherapy).
The activity of ribonucleotide reductase (RR) extracted from normal and leukemic human lymphocytes was assessed. The activity of the enzyme was five times higher in leukemic cells than in normal lymphocytes. Fe and Cu stimulated and Zn inhibited RR activity in both types of cells. Zn also partially reduced the stimulatory effects of Fe and Cu. Deferoxamine (DFX) alone inhibited the activity of the enzyme and enhanced a similar inhibitory action of hydroxyurea (HU). In both cases the inhibitory effects were reversed by Fe and Cu, but not Zn. These findings suggest that: 1) Fe, Cu and Zn may modulate RR activity in vitro and their action is related and interdependent. 2) DFX alone may inhibit RR activity. 3) DFX enhances HU effect on leukemic cells. 4) The effects of both inhibitors may be modified by trace metals.
To evaluate the modulatory effects of trace metals on lymphocyte growth and maturation, thymidine uptake (TU), protein, ATP, Fe, Cu, Zn, ferritin, CD3, CD4, CD8 antigens, surface transferrin receptors (TFR) and interleukin 2 receptors (IL2R) were assessed in normal and T cell leukemia human lymphocytes, cultured in media with varying Fe, Cu and Zn concentrations [Me]. In normal lymphocytes in media with optimal [Me], all values increased significantly after PHA stimulation, except for intracellular metal concentration and CD3+, CD4+, CD8+ cells which were unchanged. In media with low or high [Me], all parameters except for CD8+ cells were decreased. In unstimulated ALL lymphocytes grown in media with optimal [Me], TU, protein, ATP, CD4+, Fe, Cu and ferritin were higher and Zn and CD8+ lower than in unstimulated normal cells: they did not change after PHA stimulation, except in media with low [Me], in which they approached the values of stimulated normal lymphocytes. TFR and IL2R for ALL cells were high in all media: IL2R but not TFR increased after PHA stimulation. No relationship between IL2R and TFR was demonstrable in any media. We conclude that the response of normal lymphocytes to stimuli is sensitive to variation in trace metals, whereas this response, absent in ALL lymphocytes, reappears only in media with low [Me] and is independent from TFR.
Lymphocytes of children with T cell and pre-B cell acute lymphocytic leukemia (ALL) were cultured in media with different concentrations of Fe, Cu and Zn to detect a possible effect of these ions on leukemic cells. Thymidine uptake was elevated in non-mitogen stimulated ALL cells and increased after mitogen stimulation, whereas intracellular ferritin, Fe and Cu, elevated before culture, decreased thereafter; pre-B ALL cells, positive only for cytoplasmic mu chains, became positive for surface immunoglobulins and released a detectable amount of them; low T4/T8 ratio in cells from T cell ALL returned to normal values after culture. These findings were present only in media with minimal concentrations of Fe, Cu and Zn and suggest that regulation of intracellular levels of these metals may induce some differentiation of leukemic cells.