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C Orsini

Publications and source records attributed to C Orsini.

26 records · Page 2Linked to original sources
PubMed1998

Parallel strain-dependent effect of amphetamine on locomotor activity and dopamine release in the nucleus accumbens: an in vivo study in mice.

Vulnerability to develop drug abuse could be related to differential sensitivity to some central effects of such drugs. Several results point to mesoaccumbens dopamine release elicited by psychostimulants as the rate-limiting factor of their reinforcing, hence addictive, effects and to locomotor stimulation as an indirect index of such a response. In this paper, we report parallel differences in sensitivity to amphetamine-induced locomotor stimulation and mesoaccumbens dopamine release in two inbred strains of mice characterized by differential susceptibility to develop drug self-administration. Thus, mice of the C57BL/6 strain responded with a simultaneous increase of locomotor activity and mesoaccumbens dopamine release measured by intracerebral microdialysis to amphetamine challenge. On the contrary, mice of the DBA/2 strain did not present either response. No strain differences in mesoaccumbens dopamine outflow or 3,4-dihydroxyphenylacetic acid concentration were found in basal conditions or following saline challenges. However, mice of the C57BL/6 strain were characterized by higher levels of accumbal homovanillic acid in basal conditions, in line with the results obtained in rats rendered more sensitive to the locomotor effects of psychostimulants by repeated administration. Finally, in both strains amphetamine decreased accumbal levels of the two metabolites. These results suggest that genotype modulates the locomotor effects of amphetamine through sensitivity of the mesoaccumbens system to amphetamine-stimulated dopamine release. Moreover, they provide a basis to test the hypothesis of mesoaccumbens dopamine involvement in individual susceptibility to the addictive effects of drugs by quantitative trait loci analysis in recombinant inbred strains.

Amphetamine↗
PubMed1997

Recombinational construction in Escherichia coli of infectious adenoviral genomes.

A two-step gene replacement procedure was developed that generates infectious adenoviral genomes through homologous recombination in Escherichia coli. As a prerequisite, a human adenovirus serotype 5 (Ad5)-derived genome was first introduced as a PacI restriction fragment into an incP-derived replicon which, in contrast to ColE1-derivatives (e.g., pBR322 or pUC plasmids), is functional in a polA mutant of E. coli. Any modification can be introduced at will following two consecutive homologous recombinations between the incP/Ad5 replicon and the ColE1 plasmid. The overall procedure requires only the in vitro engineering of the ColE1-derivative by flanking the desired modification with small stretches of identical sequences. In the first step, a cointegrate between the tetracycline-resistant incP/Ad5 replicon and the kanamycin-resistant ColE1-derivative is selected by growing the polA host in the presence of both antibiotics. Resolution of this cointegrate is further selected in sucrose growth conditions due to the loss of a conditional suicide marker (the sacB gene of Bacillus subtilis) present in the ColE1 plasmid, leading to unmodified and modified incP/Ad5 replicons that can be differentiated upon restriction analysis. Consecutive rounds of this two-step cloning procedure allowed the introduction of multiple independent modifications within the virus genome, with no requirement for an intermediate virus. The potential of this procedure is demonstrated by the recovery of several E1E3E4-deleted adenoviruses following transfection of the corresponding E. coli-derived genomes in IGRP2 cells.

Adenovirus E1 Proteins↗
PubMed1997

Long-term gene delivery into the livers of immunocompetent mice with E1/E4-defective adenoviruses.

We have compared the in vitro and in vivo behaviors of a set of isogenic E1- and E1/E4-defective adenoviruses expressing the lacZ gene of Escherichia coli from the Rous sarcoma virus long terminal repeat. Infection of tumor-derived established cell lines of human origin with the doubly defective adenoviruses resulted in (i) a lower replication of the viral backbone that correlated with reduced levels of E2A-specific RNA and protein, (ii) a significant shutoff of late gene and protein expression, and (iii) no apparent virus-induced cytotoxicity. Independently of the extent of the deletion, the additional inactivation of E4 from the viral backbone therefore drastically disabled the virus in vitro, with no apparent effect on transgene expression. A lacZ-transgenic model was used to compare the different recombinant adenoviruses in the livers of C57BL/6 mice. The immune response to the virally encoded beta-galactosidase was minimal in this model, as infusion of the E1-defective adenovirus resulted in a time course of transgene expression that mimicked that in immunodeficient (nu/nu) mice, with very little inflammation and necrosis in the liver. Administration of a doubly defective adenovirus to the transgenic animals led to long-term extrachromosomal persistence of viral DNA in the liver, with no detectable methylation of CpG dinucleotides. However, transient transgene expression was observed independently of the extent of the E4 deletion, suggesting that the choice of the promoter may be critical to maintain transgene expression from these attenuated adenovirus vectors.

Adenoviridae↗
PubMed1996

Efficient dual transcomplementation of adenovirus E1 and E4 regions from a 293-derived cell line expressing a minimal E4 functional unit.

Transgene expression after the administration of recombinant adenovirus with E1 deleted is constantly transient. It is admitted that E1A-substituting activities of cellular or viral origin allow viral antigen synthesis and trigger cytotoxic lymphocyte-mediated clearance of the recipient cells. Our approach to solving this problem relies on the additional deletion of the E4 region from the vector backbone as this region upregulates viral gene expression at both transcriptional and posttranscriptional levels. As a prerequisite to the construction of E1 E4 doubly defective adenoviruses, we investigated the possibility of transcomplementing both functions within a single cell. In particular, the distal ORF6+ORF7 segment from the E4 locus of adenovirus type 5 was cloned under the control of the dexamethasone-inducible mouse mammary tumor virus long terminal repeat. Following transfection into 293 cells, clone IGRP2 was retained and characterized as it can rescue the growth defect of all E1+ E4- adenoviral deletants tested. DNA and RNA analysis experiments verified that the mouse mammary tumor virus promoter drives the expression of the ORF6+ORF7 unit and permits its bona fide alternative splicing, generating ORF6/7 mRNA in addition to the ORF6-expressing primary transcript. Importantly, IGRP2 cells sustain cell confluence for a period longer than that of 293 parental cells and allow the plaque purification of E1- or E4- defective viruses. The dual expression of E1 and E4 regulatory genes within IGRP2 cells is demonstrated by the construction, plaque purification, and helper-free propagation of recombinant lacZ-encoding doubly defective adenoviruses harboring different E4 deletions. In addition, the emergence, if any, of replicative particles during viral propagation in this novel packaging cell line will be drastically impaired as only a limited segment of E4 has been integrated.

Adenovirus E1 Proteins↗
PubMed1985

An automated apparatus for the study of visual discriminations in pigeons.

A fully automated apparatus for the study of visual discriminations in pigeons is described. The apparatus allows the presentation of a single stimulus for successive discriminations and of two or more stimuli at the same time for simultaneous discriminations. It has proven advantageous for comparing successive and simultaneous discriminations in tests of interocular transfer.

Animals↗
PubMedDate not supplied

[Rare association of a mixed tumor of the skin with a carcinoma of low grade malignancy. Clinical case].

Chondroid syringoma, previously called mixed tumor of the skin is a fairly uncommon type of sweat gland tumor, most often diagnosed in the sixth and seventh decade of life. It presents as a well encapsulated dermal or subcutaneous module and it is most frequently found in the skin of the head and neck. The neoplasm is asymptomatic and is featured by a slow rate of growth. At histopathological examination, the tumor consists of an epithelial component, with glandular or ductal differentiation, either eccrine or apocrine, and a stromal component with myxoid or chondroid elements. Surgical removal is the treatment of choice and recurrence may occur. Malignant chondroid syringoma has been reported rarely, most frequently arising in previously benign lesions. They behave as lethal tumors and often metastasize to the regional lymph nodes and lung. We report a most unusual case of a mixed tumor of the skin localized in the sacral area associated with a peripheral low grade malignant component of the adenocystic type. Association of these two types of sweat gland tumors has never been previously described, to our knowledge.

Adenoma, Pleomorphic↗