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A Poma

Publications and source records attributed to A Poma.

36 records · Page 2Linked to original sources

Sister chromatid exchange (SCE) rates in human melanoma cells as an index of mutagenesis.

Melanomas are highly clonogenic. Genetic variability and polymorphism of tumour cell populations have been reported. However, no direct evidence of mutator activity as a source of genetic polymorphism for melanoma cells has been described. Some intermediates of melanin synthesis are cytotoxic and genotoxic and their mutagenic power has been described. We show here that the rate of sister chromatid exchange (SCE) of the line of human melanoma cells used varies with the concentration of the melanin precursor L-tyrosine, in the culture medium. An increase of melanin synthesis results in increased SCE rates. The highest values of SCEs are found in melanotic melanoma cells compared with the amelanotic ones. Indeed we present evidence that melanoma cells show higher levels of SCE when compared with normal human lymphocytes, and to the SCE frequencies derived from the literature on the lymphocytes of familial malignant melanoma, sporadic malignant melanoma patients and the lymphocytes of relatives of familial and sporadic melanoma patients.

Culture Media↗

Cyto-genotoxic species leakage within human melanoma melanosomes. Molecular-morphological correlations.

This work studies the phenotype changes, relating to pigment expression, of a human melanoma cell line. The phenotypic instabilities and proliferation rates are correlated with the production and release in the cell culture medium of active oxygen species and melanin synthesis intermediates. The proliferation rates versus L-tyrosine concentration in the culture media are investigated: a decrease is found when high L-tyrosine is added to the medium. This would be consistent with the release of cytotoxic and/or genotoxic species by melanoma cells. The morphology of melanoma melanosomes is coherent with the leakage of cytotoxic and genotoxic species produced during melanin synthesis.

Cell Division↗

Developmental aspects of Bufo bufo embryo glutathione transferases.

The expression of glutathione transferase isoenzymes has been studied during the development of Bufo bufo embryo. By analysing the GSH-affinity purified materials in terms of substrate specificities, SDS-PAGE pattern, HPLC elution profile, we conclude that, up to stage 22, no significant changes in the expression of glutathione transferases isoenzymes occurred during Bufo bufo embryo development. At stage 25 the distribution of glutathione transferases was found to be slightly different from those of all other foregoing stages. A marked decrease of embryonic glutathione transferases subunits with a parallel appearance of new structurally and immunologically different subunits was noted in toad liver and kidney. Toad ovary continued to express embryonic glutathione transferase subunits.

Animals↗

Specific increase of L-dopa levels in plasma upon infusion of tyrosinase containing liposomes.

1. The present paper reports the effects of liposome-entrapped tyrosinase (EC 1.14.18.1. L-Tyrosine, L-3,4-dihydroxyphenylalanine: oxygen oxidoreductase) infusion on the catecholamine contents of rat plasma. The actions of liposomes and free tyrosinase have also been investigated. 2. From the experiments, evidence has been obtained that liposome-entrapped tyrosinase is able to affect specifically L-3,4-dihydroxyphenylalanine (L-DOPA) levels which increase dramatically. 3. The possible use of liposome-entrapped tyrosinase to raise L-DOPA levels in catecholamine related disorders is discussed. 4. Liposomes without tyrosinase provoke no significant changes of catecholamine or L-DOPA levels while free tyrosinase does induce a change but in a less constant fashion than the liposome-entrapped enzyme.

Animals↗

Glutathione transferase isoenzymes from Bufo bufo embryos at an early developmental stage.

Six forms of glutathione transferase (GST) were resolved from the cytosolic fraction of Bufo bufo embryos at developmental stage 4 by GSH-Sepharose affinity chromatography followed by f.p.l.c. chromatofocusing in the 9-6 pH range. They have apparent isoelectric points at pH 8.37 (GST I), 8.22 (GST II), 8.10 (GST III), 7.84 (GST IV), 7.37 (GST V) and 7.12 (GST VI), and each displayed an apparent subunit molecular mass of 23 kDa by SDS/PAGE. The Bufo bufo embryo enzymes showed very similar structural, catalytic and immunological properties, as indicated by their substrate-specificities, inhibition characteristics, c.d. spectra, h.p.l.c. elution profiles and immunological reactivities, as well as by their N-terminal amino acid sequences. Although Bufo bufo embryo GSTs do not correspond to any other known GSTs, the results of our experiments indicate that amphibian GSTs could be included in the Pi family of GSTs. This conclusion is supported by the analysis of c.d. spectra, and by the fact that mammalian Pi class GSTs and amphibian GSTs showed about 80% identity in their N-terminal amino acid sequences. Furthermore, antisera prepared against Bufo bufo GST III cross-reacted in immunoblotting analysis with Pi class GSTs, and vice versa.

Amino Acid Sequence↗

Comparisons of tetrachloro(d,l-trans)1,2-diaminocyclohexane-platinum(IV) biotransformations in the plasma of Fischer 344 rats at therapeutic and toxic doses.

Plasma biotransformations of tetrachloro(d,l-trans)1,2-diaminocyclohexaneplatinum(IV) (tetraplatin) were determined in vivo at both therapeutic (3 mg/kg) and toxic (12 mg/kg) doses in Fischer 344 rats. Tetraplatin was rapidly converted to dichloro(d,l-trans)1,2-diaminocyclohexaneplatinum(II) [PtCl2(dach)]. This conversion was complete at the earliest time measured (7.5 min) at the therapeutic dose, but some unreacted tetraplatin was detectable in the circulation at the toxic dose. Three other major biotransformation products were observed in plasma: (d,l-trans)1,2-diaminocyclohexaneaquachloroplatinum(II) [Pt(H2O)(Cl)(dach)]+, the Pt-methionine complex, and another biotransformation product tentatively identified as either the Pt-cysteine or Pt-ornithine complex. Several other minor plasma biotransformation products were detected. Two of these were most likely formed intracellulary from tetraplatin. Two or more other platinum complexes appeared to lack the diaminocyclohexane carrier ligand and were most likely formed intracellulary by trans-labilization of the carrier ligand. Tetraplatin, PtCl2(dach), and [Pt(H2O)(Cl)(dach)]+ all rapidly disappeared from the circulation. The other biotransformation products were persistent through at least 3 h and could be responsible for the delayed toxicity of tetraplatin. Although some minor differences were observed between tetraplatin biotransformations at the toxic vs therapeutic doses, most biotransformation products were simply present at much greater concentrations at the toxic dose than at the therapeutic dose. Thus, our data suggest that dose-dependent differences in tetraplatin toxicity are probably attributable to the amount, rather than the type, of biotransformation products present in the plasma.

Animals↗

Mutagenicity test for unstable compounds, such as 5,6-dihydroxyindole, using an Escherichia coli HB101/pBR322 transfection system.

A mutagenicity test for unstable chemical compounds has been devised. The test makes use of (i) in vitro treatment of plasmid pBR322 with the putative mutagen (ii) subsequent transfection of Escherichia coli HB101; (iii) selection either on tetracycline- or ampicillin-containing Eugon agar (iv) cross-antibiotic replica plating and recovery of single antibiotic resistant colonies (v) restriction analysis of pBR322 isolated from single antibiotic resistant colonies. In this work the test has been used to assess the mutagenicity of 5,6-dihydroxyindole, a cytotoxic intermediate of melanin biosynthesis.

Ampicillin Resistance↗

Liposome-entrapped tyrosinase: a tool to investigate the regulation of the Raper-Mason pathway.

The effect of the entrapment of mushroom tyrosinase (EC 1.14.18.1) within liposomes on the enzyme activity and Km vs. L-3,4-dihydroxyphenylalanine is reported in the present work; the effect of cholesterol insertion within liposome membranes on the enzyme activity has also been studied. The oxidation rates of various monophenols and diphenols by free and liposome-integrated mushroom tyrosinase were measured and the oxidation latencies vs. different substrates investigated. The different substrates are apparently oxidized according to the properties of the substituents as electron donors or acceptors; the Km values vs. L-3,4-dihydroxyphenylalanine calculated on measuring O2 consumption are higher than those calculated on measuring the dopachrome production rates. It is interesting that natural substrates of tyrosinase are oxidized according to a negative catalysis by the liposome-entrapped enzyme; this point is discussed in relation to the well known cytotoxicity of some intermediates of the Raper-Mason pathway.

Basidiomycota↗

Effects of supidimide in schizophrenic inpatients undergoing neuroleptic maintenance therapy with haloperidol.

Forty schizophrenic inpatients, on constant low-dosage maintenance therapy with haloperidol, entered a superimposed, double-blind, placebo-controlled clinical trial with supidimide 2 x 200 mg per day. The double-blind phase lasted 5 days and was preceded and followed by single-blind base line and washout periods, respectively, during which all patients received matching placebos. The therapeutic effects were evaluated by BPRS, NOSIE, a post-sleep questionnaire, and, in a subgroup of patients, by objective monitoring of movements during sleep. Supidimide substantially relieved sleep disturbances, as demonstrated by subjective (p less than 0.05; n = 20) and objective (p less than 0.1; n = 3) measurements. In addition, the following drug-related effects (p less than 0.05 versus base line and placebo) on daytime behaviour were observed: a decrease in "somatic concern" (BPRS), items related to agitation (BPRS), "irritability" and "manifest psychosis" (NOSIE), and a slight increase in "retardation" (NOSIE). No adverse effects attributable to supidimide were detected. It is concluded that supidimide exerts beneficial effects on day-time behaviour and sleep in agitated schizophrenic patients undergoing low-dosage maintenance neuroleptic therapy.

Adult↗

Changes of lipo-melanosome membrane leakage versus pH, charge and composition.

Liposome models of melanosomes (lipo-melanosomes) were used to investigate how phospholipid composition, charge and medium pH may affect the lipo-melanosome membrane permeability to active oxygen species or melanin synthesis intermediaries. Active oxygen accumulated only at pH 6.4 and was polarographically monitored using superoxide dismutase and/or catalase. Cholesterol appears to increase the O2- accumulation at pH 6.4 while incorporation of positive phospholipids within lipo-melanosomes results in the loss of latency with respect to tyrosinase substrate and intermediates of melanin synthesis.

Catalase↗

[Indications for hepatic resection: personal experience].

The Authors, before examining their case history, which includes 103 major and minor hepatic resections performed during the last decade, briefly show the surgical technique concerning hepatic ischaemia and the new technologies proposed to reduce the hematic loss during hepatic resections. The constant adoption of these techniques and the careful evaluation of some parameters concerning hepatic functionality allowed to decrease postoperative complications and mortality, which currently is around 5-10%. These data are confirmed by the Authors experience.

Animals↗