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A C Ferrari

Publications and source records attributed to A C Ferrari.

25 records · Page 2Linked to original sources
PubMed1990

The effect of phentolamine on the pressor response to centrally administered clonidine in rats.

In the present study we investigate the effect of the previous injection of phentolamine (a nonspecific alpha-adrenergic antagonist) into the lateral hypothalamus (LH) and lateral ventricle (LV) on the pressor and bradycardic responses produced by the injection of clonidine (an alpha 2-adrenergic agonist) into these same areas of conscious rats. The injection of clonidine into the LV and LH produced pressor (39 +/- 5 and 38 +/- 3 mmHg, respectively) and bradycardic responses (-65 +/- 16 and -94 +/- 13 bpm, respectively). Previous injection of phentolamine into the LH or LV reduced the pressor response to clonidine injected into the same areas (delta MAP = 13 +/- 6 mmHg for LH and 1 +/- 3 mmHg for LV). No reduction was observed when clonidine was injected into the LV after the injection of phentolamine into the LH. No changes in bradycardic responses were observed after treatment with phentolamine. The present results show the participation of alpha-adrenergic receptors in the pressor response to centrally administered clonidine but not in the bradycardic response. The data also suggest that the pressor effect produced by the injection of clonidine into the LH is due to the activation of alpha-adrenergic receptors located specifically in this area. The pressor response after injection of clonidine into the LV and of phentolamine into the LH is due to the action of clonidine on other cerebral areas.

Animals↗
PubMed1988

The FGF-related oncogene, K-FGF, maps to human chromosome region 11q13, possibly near int-2.

The protein encoded in a novel human oncogene isolated by transfection of Kaposi's sarcoma DNA is a growth factor with significant homology to basic and acidic FGFs. The genomic structure of this oncogene (designated K-FGF), as originally isolated, carried DNA rearrangements upstream and downstream of the coding region. The normally discontinuous sequence upstream of the K-FGF coding region derived from the 3' end of the c-fms gene and thus originated from human chromosome 5. In order to determine the normal chromosomal location of the K-FGF gene and of the DNA sequences adjacent to its 3' end, we have correlated the presence of these sequences with retention of specific human chromosome regions in rodent-human somatic cell hybrids. These experiments mapped the K-FGF gene to human chromosome region 11q13----11q23, and in situ hybridization localized it more precisely to region 11q13 near int-2, which also belongs to the FGF family. The sequence downstream of the gene in transfectants and discontinuous with K-FGF in normal human DNA derives from chromosome region 12p12----12q13, possibly near the int-1 locus.

Chromosome Mapping↗
PubMed1985

Characterization of differentiation-inducer-resistant HL-60 cells.

Sub-lines of the cultured human promyelocytic leukemia cell line HL-60 were individually selected for their ability to sustain exponential growth in the presence of 3 structurally-unrelated inducers of granulocytic differentiation - retinoic acid (RA), dimethylsulfoxide (DMSO), and 6-thioguanine (6TG). Selections were made by step-wise augmentation to final drug concentrations of 10(-3)mM RA, 169mM (1.2%) DMSO and 0.12mM (20 micrograms ml-1) 6TG. In addition to growth resistance, cells in each sub-line displayed variable cytodifferentiation resistance to each of the 3 selective agents, which was quantitated as the ratio of the concentration of drug required to induce differentiation in 50% of the cells in each resistant sub-line versus comparably-passaged wild-type HL-60 cells. The levels of resistance/cross-resistance were as follows: RA-resistant (res) sub-line greater than 2700-fold to RA, 1.3-fold to DMSO and greater than 1.5-fold to hypoxanthine (HXN; the noncytotoxic purine base inducer analogue of 6TG); DMSO-res sub-line 2.5-fold to DMSO, 137-fold to RA and greater than 1.5-fold to HXN; and 6TG-res sub-line greater than 1.5-fold to HXN, 9-fold to RA and 1.6-fold to DMSO. These sub-lines were not cross-resistant to sodium butyrate (NaBut), a monocyte inducer, or to 12-0-tetradecanoylphorbol 13-acetate (TPA), a macrophage inducer. HL-60 sub-lines selected by exposure to a single high concentration of 5-bromo-2'-deoxyuridine (BUdR; 3.3 X 10(-2)mM) or oubain (Ou; 5 X 10(-3)mM) were not or were slightly cross-resistant to either granulocyte or monocyte inducers. Although some variations in line/sub-line phenotype were observed, this was minor compared to the quantitative variations in response to individual inducing agents. The RA-res and 6TG-res sub-lines contained numerous double minute chromosomes (indicators of amplified genes) which were either absent or present in much smaller numbers in the parental wild-type cells or in the other drug-resistant sub-lines. There was little change or a decrease in the amplification level of the known amplified oncogene c-myc in the various drug-resistant sub-lines compared to wild-type HL-60 cells. These results (a) confirm that the neutrophilic granulocytic and monocytic/macrophagic differentiation programs in HL-60 cells are mechanistically different and separable; (b) suggest that both agent-specific and common quantitative alterations contribute to the mechanism(s) for resistance to granulocyte differentiation; and (c) suggest that the latter quantitative defects could be related to amplification of genes other than c-myc.

Bromodeoxyuridine↗
PubMed1984

Cytotoxic and cytodifferentiative components of 6-thioguanine resistance in HL-60 cells containing acquired double minute chromosomes.

As an experimental strategy for potentially dissociating and studying the cytotoxic and cytodifferentiative antileukemic effects of 6-thioguanine (6-TG), cultured human promyelocytic leukemia cells (HL-60) were serially selected for growth in increasing concentrations of 6-TG (0.5 to 50 micrograms/ml). Three acquired characteristics, cytotoxic resistance, cytodifferentiative resistance, and double minute chromosomes (DM), were monitored at successive 6-TG selection levels. Approximately 200-fold resistance to the cytotoxic effect of 6-TG was acquired at the first selection step, and it neither increased at higher 6-TG selection levels nor reverted to greater sensitivity in cells subcultured off of drug. This was due to the irreversible loss of hypoxanthine-guanine phosphoribosyltransferase (HPRT) activity. In contrast, a lesser, not completely quantifiable, degree of resistance developed to the cytodifferentiative effects of the purine nucleobases hypoxanthine and 6-TG which varied as a function of 6-TG selection pressure. Numerous DM, not observed in the parental wild-type HL-60 cells, appeared at 6-TG (0.5 micrograms/ml) selection which varied substantially in parallel with 6-TG selection pressure up to 6-TG (20 micrograms/ml). At higher selection levels (50 micrograms/ml or prolonged culture on 20 micrograms/ml), a marked decrease in DM occurred which was associated with the acquisition of new marker chromosomes. The most consistent marker was a chromosome 6 with additional material in the short arm (6p+); this was noted as a single copy in the basal 6-TG/20 subline but as two copies (trisomy 6; 2p+) in independently selected higher 6-TG-resistant subcultures. These cytogenetic findings suggest the presence of amplified genes which increased in number and shifted from a predominance in extra-chromosomal DM to intrachromosomal sites as a function of 6-TG selection. Among the 6-TG-resistant sublines, there was no change or a decrease in the amplification level of the known amplified oncogene c-myc from that demonstrated in parental HL-60 cells. Although proof requires detailed analyses with specific gene probes, the overall results imply that: (a) the cytotoxic component of the resistance is due to an invariant loss of HPRT which, therefore, is not likely to be related to amplified genes; (b) the cytodifferentiative component of the resistance is due to a positively selectable mechanism which could be directly or indirectly related to 6-TG-selected amplified genes; and (c) variations in the cytogenetic indicators of amplified genes and the resistance to 6-TG cannot be simply ascribed to quantitative variations in c-myc amplification.

Animals↗
PubMedDate not supplied

Cytogenetic methodologies for gene mapping and comparative analyses in mammalian cell culture systems.

Presented here are the detailed methods employed in our laboratory for gene mapping and cytogenetic analyses in human beings, in the domestic cat, and in other mammalian species. Induced in the procedures are: 1) establishment of primary fibroblast and lymphoid cell cultures; 2) heterologous cell fusion for production of rapidly proliferating cell hybrids; 3) cellular transformation of primary fibroblasts using an oncogenic retrovirus; 4) cell synchronization for high-resolution banding of promethaphase chromosomes; 5) chromosome-banding procedures, including G-banding, alkaline G-11, and Q-banding; and 6) in situ hybridization of radiolabeled molecular clones to metaphase chromosomes for regional gene localization.

Animals↗