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Biomedical subjects

F Bernardi

Publications and source records attributed to F Bernardi.

At least 235 records · Page 13Linked to original sources
PubMed1986

Properties of 3H-MPTP binding sites in human blood platelets.

Our study demonstrates that 3H-1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (3H-MPTP) specifically binds to platelet membrane sites in humans. This specific, high affinity and saturable binding has properties similar to those of 3H-MPTP binding to rat and monkey brain, with a higher affinity. Deprenyl, a specific inhibitor of MAO type B enzyme, was the most potent drug in displacing 3H-MPTP from platelet binding sites. Platelets are considered a good model for central aminergic neurons and are very rich with MAO enzymatic activity, exclusively of type B. Our findings support previous evidence indicating a correspondence between 3H-MPTP binding sites and MAO-B enzyme. Moreover the presence of 3H-MPTP binding sites on human platelets suggests the use of this peripheral tissue as a simple model to study at least partially the mechanisms of neurotoxic action of MPTP.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1986

High affinity binding sites for 1-methyl-4-phenyl-pyridinium ion (MPP+) are present in mouse brain.

The possible involvement of 1-methyl-4-phenyl-pyridinium ion (MPP+) in the toxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) prompted us to search for and characterize [3H]MPP+ binding sites in the mouse. Our data show that [3H]MPP+ binds saturably and with high affinity to mouse brain membranes. Scatchard analysis resulted in one straight line. The apparent KD was 15 +/- 1 nM and the Bmax 245 +/- 30 fmol/mg protein. The distribution of [3H]MPP+ binding sites shows a regional variation: the hypothalamus having highest binding and the cerebellum the lowest. Several compounds failed to inhibit [3H]MPP+ binding whereas only analogues of MPP+, MPTP and paraquat were able to antagonize this binding to brain. Specific binding with analogous characteristics also occurs in peripheral tissues. Considering the postulated role of MPP+ in MPTP neurotoxicity, further studies on [3H]MPP+ binding sites might be relevant to elucidate the mechanisms of this toxicity.

1-Methyl-4-phenylpyridinium↗
PubMed1986

Involvement of monoamine oxidase enzymes in the action of 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine, a selective neurotoxin, in the squirrel monkey: binding and biochemical studies.

1-Methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) is a new neurotoxin that causes degeneration of the dopaminergic nigrostriatal neurons and induces a Parkinson-like state in several species, including humans and monkeys. The present study was designed to better characterize the properties of [3H]MPTP binding sites and to evaluate the interaction of MPTP with the oxidation of dopamine by monoamine oxidase (MAO) in an animal species (Saimiri Sciureus) shown to be lesioned by MPTP. Our data confirm the presence of high affinity and saturable binding sites for [3H]MPTP in the squirrel monkey. Specific binding with analogous characteristics also occurs in peripheral tissues. Various substances failed to inhibit the [3H]MPTP binding, whereas only MAO inhibitors (MAOI) were able to antagonize this binding to brain and peripheral tissues. In particular, deprenyl, a selective inhibitor of MAO type B enzyme, was relatively more potent as a displacer of [3H]MPTP from its binding sites both in brain and in peripheral tissues. Our results further suggest a correspondence between [3H]MPTP sites and MAO, particularly MAO-B, in monkey brain. Moreover, our data show that the oxidative deamination of dopamine is inhibited by MPTP in vitro. In conclusion, these data are consistent with the hypothesis of the involvement of MAO in the neurotoxic effects of MPTP, even though further experiments are necessary to better clarify the molecular mechanism of MPTP neurotoxicity.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1986

Human leukemic K562 cells: suppression of hemoglobin accumulation by a monoclonal antibody to human transferrin receptor.

The receptor for transferrin plays an important role both in tumor cell growth and in hemoglobin synthesis. In this paper, we demonstrate that the monoclonal antibody 42/6 to human transferrin receptor inhibits iron uptake in the human leukemic K562 cell line and suppresses hemoglobin accumulation in K562 cells induced to erythroid differentiation by butyric acid. In contrast, only slight inhibitory effects were observed on cell proliferation of both uninduced and erythroid-induced K562 cells treated with the 42/6 monoclonal antibody. In addition, the 42/6 monoclonal antibody to human transferrin receptor does not inhibit butyric acid-induced accumulation of gamma-globin mRNA. The effect of the 42/6 monoclonal antibody on hemoglobin synthesis appears to be restricted to human cell lines, as murine Friend erythroleukemic cells undergo erythroid differentiation when cultured in the presence of hexamethylenebisacetamide plus the 42/6 monoclonal antibody. The findings reported in this paper suggest (a) a dissociation of iron transport and accumulation of heme molecules from the expression of globin genes and (b) a different requirement of iron uptake by different iron-dependent functions such as cell proliferation and hemoglobin expression.

Antibodies, Monoclonal↗
PubMed1986

Identification of a c-myc oncogene lacking the exon 1 in the normal cells of a patient carrying a thyroid carcinoma.

In this paper we describe an alteration of the c-myc oncogene present in the white blood cells and normal as well as neoplastic thyroid cells of a subject carrying a thyroid carcinoma. Restriction enzyme mapping and hybridization to human c-myc probes specific for different regions of this gene demonstrate that this subject carries, in addition to the normal one, a c-myc oncogene lacking the first exon and part of the first intron. The levels of the c-myc mRNA in thyroid cells of this subject do not show differences with respect to thyroid cells from other subjects. Taken together, these findings indicate that the deletion of the first exon of the c-myc oncogene, in itself, does not produce overtranscription of this oncogene nor hematopoietic malignancies.

Base Sequence↗
PubMed1986

Intramolecular transposition of IS102.

It has been postulated that deletions mediated by transposable elements are intramolecular transposition events. An implication of this hypothesis is that the deleted fragment may be recovered if it is capable of autonomous replication. We report here the characterization of the products of intramolecular transposition of the element IS102 in bireplicons. We show that when two origins (ori's) (of pSC101 and R6-5) generate the same copy numbers, two dissociated replicons are recovered as well as the inversions. On the contrary, when two ori's (of pSC101 and pBR322) have different copy numbers, intramolecular transposition results essentially in inversions. However, the very low frequency (5 X 10(-8)) at which intramolecular transpositions in the bireplicons occurs, as compared to the single replicon (10(-4)), suggests that a complete transposition reaction may not be necessary to generate deletions.

Chromosome Deletion↗
PubMed1986

Reproductive failure and parental chromosome abnormalities.

The effect of ascertaining on estimates of the frequency of parental chromosome abnormalities in couples with a previous history of pregnancy wastage was investigated by comparing three samples which differ in the ascertainment modality but not in the cytogenetical approach. The incidence of chromosome abnormalities was higher in the sample of 441 couples selected essentially on clinical criteria (6%) than in the two samples (659 and 479 couples) selected retrospectively from the files of two cytogenetic laboratories (4.6 and 3.2%). The comparison of these results with similar data, based on large samples reported in the literature, indicated that sample size may be relevant in producing the wide ranges of variation of the frequency of chromosomal abnormalities. Using our data and those from three other samples of greater than 300 couples a reasonable estimate of the overall incidence of chromosomal abnormalities in couples with a previous history of fetal wastage is approximately 5%.

Abortion, Habitual↗
PubMed1986

Methylation and expression of c-myc and c-abl oncogenes in human leukemic K562 cells before and after treatment with 5-azacytidine.

The correlation between expression and extent of DNA methylation of c-myc and c-abl oncogenes has been investigated in the human leukemic K-562 cell line before and after 5-azacytidine-mediated erythroid induction. RNA accumulation was analyzed by cytoplasmic dot hybridization and DNA methylation by using HpaII and MspI endonucleases, which differently cleave the CCGG sequence depending on cytosine methylation. Both the oncogenes are expressed in uninduced cells; however, whereas the c-myc expression does not change following 5-azacytidine treatment, the c-abl expression sharply decreases. The HpaII pattern shows that the c-myc DNA region is undermethylated and that the c-abl gene is hypermethylated both before and after the erythroid induction. Nevertheless, in both the genes 5-azacytidine produces variations in the MspI pattern compatible with mCmCGG to CmCGG demethylations.

Azacitidine↗
PubMed1985

Mapping of human thyroglobulin gene on the long arm of chromosome 8 by in situ hybridization.

We report the structural organization of a segment of the human thyroglobulin gene, located 70kb from the 3' end of the gene, containing the exons 8 and 9 starting from the 3' end. Selected probes from this region have been used for the chromosomal mapping of the thyroglobulin gene by in situ hybridization techniques. Only one site in the human haploid karyotype is labeled with the genomic DNA probes. Twenty percent of the grains are localized on the long arm of chromosome 8, mostly in the subregion q-2-23 q-2-24 of the long arm of chromosome 8. The localization of the autoradiographic grains suggests a subregional assignment of the human thyroglobulin gene locus to 8q 2-23 or 8q 2-24.

Base Sequence↗