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Biomedical subjects

L Basilico

Publications and source records attributed to L Basilico.

At least 19 recordsLinked to original sources
PubMed1999

Cross-tolerance and convergent dependence between morphine and cannabimimetic agent WIN 55,212-2 in the guinea-pig ileum myenteric plexus.

The cross-tolerance and convergent dependence between morphine and the cannabimimetic agent R(+)-[2,3-dihydro-5-methyl-3[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-+ ++benzoxazin-yl]-(1-naphthalenyl) methanone mesylate (WIN 55,212-2) were assessed in vitro on guinea-pig ileum. To induce tolerance and dependence the myenteric plexus-longitudinal muscle was incubated at 37 degrees C for 5 h with a fixed concentration representing the IC50 for each compound. Myenteric plexus-longitudinal muscle exposed to WIN 55,212-2 (5 x 10(-8) M) was less sensitive to its inhibitory effect on electrically evoked contractions than naive myenteric plexus-longitudinal muscle. The exposure to cannabinoid induced a parallel rightward shift in the lower part of the concentration-response curve of WIN 55,212-2 and a marked reduction in the maximal inhibitory effect of the drug. Myenteric plexus-longitudinal muscle tolerant to WIN 55,212-2 was subsensitive to the inhibitory effect of morphine on the twitch response. The cross-tolerance between WIN 55,212-2 and morphine was bidirectional. In fact, after 5 h the morphine (10(-7) M)-incubated myenteric plexus-longitudinal muscle was less sensitive to the inhibitory effect of WIN 55,212-2. The tissue tolerant to morphine or WIN 55,212-2 was tested for the presence of physical dependence. Naloxone (10(-5) M) produced a typical withdrawal contracture in morphine-tolerant myenteric plexus-longitudinal muscle which could be reduced by a 15-min pretreatment with WIN 55,212-2 (5 X 10(-8) M). In contrast, SR141716 (10(-6) M) [N-(piperidino)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyr azole-carboxamide], a concentration which fully antagonized the inhibitory effect of WIN 55,212-2 (10(-7) M) in control preparations, did not produce significant contracture in WIN 55,212-2-tolerant myenteric plexus-longitudinal muscle. The mechanisms underlying the cross-tolerance and convergent dependence remain to be ascertained.

Analgesics, Opioid↗
PubMed1997

Cholera toxin effects on body temperature changes induced by morphine.

The present study evaluates the influence of cholera toxin and its B-subunit on thermic responses to morphine in the rats. The holotoxin (1 microg/rat) and the B-subunit (5 microg) were administered ICV and three days later rats were challenged ICV with morphine and tested for changes of body temperature. Cholera toxin, but not its B-subunit, modified the time course of the hyperthermic response induced by a low dose of morphine (2.5 microg), converted the hypothermia due to a higher dose of morphine (18 microg) to a consistent hyperthermia and only partially reduced the greater hypothermia induced by 36 microg of morphine. Cholera toxin-induced modifications of thermic responses to morphine were paralleled with a decreased Gs(alpha) immunoreactivity and a reduced ability for the toxin to catalyse the "in vitro" ADP-ribosylation of Gs(alpha) in hypothalamic membranes. In contrast, at the same time when morphine-induced effects on body temperature were assessed, no changes in pertussis toxin-mediated ADP-ribosylation of Gi(alpha)/Go(alpha), or basal adenylate cyclase activity, or binding of mu-opioid receptor selective ligand [3H]-DAMGO were observed in hypothalamic areas from rats treated with cholera toxin. These findings suggest that adaptative events secondary to prolonged activation of Gs(alpha) play a role in the modifications of thermic responses to morphine induced by CTX.

Adenosine Diphosphate Ribose↗
PubMed1997

Molecular heterogeneity of regulatory elements of the mouse GATA-1 gene.

The GATA-1 gene encodes a transcription factor expressed in early multipotent haemopoietic progenitors, in more mature cells of the erythroid, megakaryocytic and other lineages, but not in late myeloid precursors; its function is essential for the normal development of the erythroid and megakaryocytic system. To define regulatory elements of the mouse GATA-1 gene, we mapped DNaseI-hypersensitive sites in nuclei of erythroid and haemopoietic progenitor cells. Five sites were detected. The two upstream sites, site 1 and site 2, represent a new and a previously defined erythroid enhancer respectively. The site 1 enhancer activity depends both on a GATA-binding site (also footprinted in vivo) and on several sites capable of binding relatively ubiquitous factors. A DNA fragment encompassing site 1, placed upstream of a GATA-1 minimal promoter, is able to drive expression of a simian virus 40 (SV40) T-antigen in the yolk sac, but not bone-marrow cells, obtained from mice transgenic for this construct, allowing in vitro establishment of immortalized yolk-sac cells. A similar construct including site 2, instead of site 1, and previously shown to be able to immortalize adult marrow cells is not significantly active in yolk-sac cells. Sites 4 and 5, located in the first large intron, have no enhancer activity; they include a long array of potential Ets-binding sites. MnlI restriction sites, overlapping some of the Ets sites, are highly accessible, in intact nuclei, to MnlI. Although these sites are present in all GATA-1-expressing cells studied, they are the only strong sites detectable in FDCP-mix multipotent progenitor cells, most of which do not yet express GATA-1. The data indicate that appropriate GATA-1 regulation may require the co-operation of different regulatory elements acting at different stages of development and cell differentiation.

Animals↗
PubMed1997

Redundant functions of B-Myb and c-Myb in differentiating myeloid cells.

We show in this report that the human myeloid leukemia cell line GFD8 is a useful model to compare the biological function of the structurally related c-Myb and B-Myb proto-oncogenes and to investigate the c-myb domains required for this function. GFD8 cells are dependent for growth on granulocyte-macrophage colony-stimulating factor and differentiate in response to phorbol myristate acetate (PMA). We have stably transfected this cell line with constructs constitutively expressing c-Myb or B-Myb. Deregulated expression of both c-Myb and B-Myb inhibited the differentiation observed in response to PMA and, in particular, the induction of the CD11b and CD11c antigens on the cell surface, and the induction of adherence. Furthermore, c-Myb and B-Myb enhanced expression of CD13 upon PMA treatment. Although deregulated Myb expression did not alter the growth factor dependence of the cells, it led to an increase in G2 relative to G1 arrest in cells induced to differentiate in response to PMA, whereas control vector-transfected cells were blocked mostly in G1. This decrease in G1 block took place despite normal induction of the cyclin-dependent kinase inhibitor protein p21 (CIP1/WAF1). Thus, GFD8 cells stably expressing the human B-Myb protein behaved in a manner indistinguishable from those stably expressing C-Myb for both differentiation and cell cycle parameters. In agreement with these findings and differently from most previous reports, transactivation assays show that B-myb can indeed act as a strong activator of transcription. Finally, we demonstrated that although the DNA-binding domain of c-myb is required for both the differentiation block and the shift in cell cycle after PMA treatment, phosphorylation by casein kinase II and mitogen-activated protein kinase at positions 11 and 12 or 532 of c-myb, respectively, are not. We conclude that c-Myb and B-Myb may activate a common cellular program in the GFD8 cell line involved in both differentiation and cell cycle control.

Antigens, Differentiation↗
PubMed1996

Regulation of hematopoietic cell proliferation and differentiation by the myb oncogene family of transcription factors.

The myb family of genes include the virally encoded v-myb oncogene, its normal cellular equivalent c-myb and two related members called A-myb and B-myb. They are all transcription factors that recognize the same DNA sequence (PyAACG/TG) and are all involved in the regulation of proliferation and differentiation in different cell types, including hematopoietic cells. C-myb is most highly expressed in hematopoietic cells and its oncogenic activation leads to transformation of these cells. Several lines of evidence have demonstrated that c-myb regulates both the proliferation and differentiation of hematopoietic cells of different lineages. The mechanisms of action of c-myb and v-myb are becoming clearer, mostly through the study of the different genes that are regulated by these transcription factors and the cofactors with which c-myb and v-myb co-operate. More recently the biological and biochemical functions of the B-myb and A-myb gene products have been investigated. Evidence for the function of the different members of the myb family in relation to hematopoietic proliferation and differentiation is presented, and the different roles of the myb genes are discussed.

Animals↗
PubMed1994

Intestinal effect of morphine 6-glucuronide: in vivo and in vitro characterization.

Morphine 6-glucuronide, a major metabolite of morphine with potent analgesic actions, is a potent inhibitor of intestinal motility when administered to rats by the intracerebroventricular (i.c.v.) route. Morphine 6-glucuronide was 62-fold more active than morphine in inhibiting gastrointestinal transit, whereas it was only 25-fold more potent in abolishing intestinal migrating myoelectric complexes. Pretreatment with naloxone (5 micrograms/rat i.c.v.) completely prevented the disappearance of migrating myoelectric complexes induced by the morphine metabolite. In contrast, in the guinea pig ileum bioassay, morphine 6-glucuronide and morphine inhibited the electrically evoked contractions of the tissue with similar potency, although in the guinea pig ileum binding assay the metabolite showed 4-fold lower affinity for the opiate receptor. The low naloxone Ke values against morphine 6-glucuronide or morphine indicated that the action of both drugs in guinea pig ileum was mediated by mu-opioid receptors.

Animals↗
PubMed1992

Influence of pertussis toxin on thermic responses to morphine and neurotensin in rats.

The influence of pertussis toxin (PTX) on thermic responses elicited by morphine and neurotensin was evaluated in unrestrained rats kept at 22 degrees C. High doses of morphine (9-36 micrograms/rat i.c.v.) lowered body temperature and low doses (1.25, 2.5 micrograms/rat i.c.v.) produced hyperthermia. The hyperthermic effect was more resistant than the hypothermic effect to naloxone antagonism. Neurotensin (50, 100 micrograms/rat i.c.v.) induced marked hypothermia followed by hyperthermia. I.c.v. injection of PTX (1 microgram), six days before morphine (18 micrograms/rat i.c.v.), replaced the opiate hypothermia by consistent hyperthermia and reduced by 60% the hyperthermia elicited by morphine (2.5 micrograms/rat i.c.v.). The toxin also affected the thermic responses induced by neurotensin (50 micrograms/rat i.c.v.) administered six days after PTX (1 microgram/rat i.c.v.). The initial hypothermia was enhanced by 173% and the late hyperthermia was fully antagonized. It thus appears that PTX-sensitive G-proteins play different roles in the molecular events underlying the thermoregulatory responses to morphine and neurotensin.

Animals↗
PubMed1992

Influence of omega-conotoxin on morphine analgesia and withdrawal syndrome in rats.

The effect of omega-conotoxin on opiate analgesia and withdrawal syndrome was investigated in rats. omega-Conotoxin given i.c.v. and i.p. caused weak analgesia in the tail-flick test. When the toxin (20 ng/rat) was given i.c.v. immediately before morphine (1.5 micrograms/rat i.c.v.) the resultant analgesic effect was additive. In contrast, the analgesia elicited by morphine (3 micrograms/rat i.c.v.) was greatly reduced after 24-h pretreatment with the toxin (20 ng/rat i.c.v.). The systemic administration of the toxin (10 micrograms/kg i.p.) did not affect morphine analgesia whether omega-conotoxin was coadministered with morphine (2.5 mg/kg i.p.) or was given 24 h before the opiate (5 mg/kg i.p.). omega-Conotoxin i.c.v. injected in morphine-dependent rats 15 min before naloxone challenge significantly attenuated the abstinence syndrome. On the contrary systemic administration of omega-conotoxin failed to suppress the morphine withdrawal syndrome. The present results suggest that omega-conotoxin affects both acute and chronic effects of morphine.

Analgesia↗
PubMed1991

Bombesin receptor antagonists. 2. Analogues based on substance P antagonists.

Although bombesin (BN) and substance P share only the C-terminal dipeptide amide, some substance P receptor antagonists are also weak bombesin receptor antagonists. In order to increase the selectivity of the antagonism for the BN receptor, a series of hybrid peptides were synthesized by the solid-phase methodology, and screened on 3T3 fibroblasts for binding and mitogenic activity. The analogues inhibiting BN-induced thymidine incorporation were further tested for peripheral (amylase release and urinary bladder contraction) and central activity (grooming behaviour).

3T3 Cells↗
PubMed1990

[Familial paragangliomas of the neck: integrated imaging and the planning of family screening].

The authors have studied a case of familial paraganglioma of the neck with integrated diagnostic methods: sonography (US) and MR imaging. They verified, through personal experience and literature review, the utility of familial diagnostic screening and of clinico-diagnostic screening planning. The main aim was to detect the elements which could help plan the screening, thus improving the early diagnosis of paragangliomas.

Adult↗
PubMed1989

Antinociceptive properties of lysozyme fragments.

The in vitro digestion of hen egg white lysozyme with artificial gastric juice gave a complex mixture of peptides, from which a peptide corresponding to the aminoacid sequence 39-53 was isolated. Its further hydrolysis with artificial enteric juice gave two smaller fragments having the aminoacid sequence 39-45 and 46-53 respectively. These products, like lysozyme, showed antinociceptive activity in rats against foot hyperalgesia induced by a subplantar injection of brewer's yeast.

Analgesics↗
PubMed1988

Cerebral extract from morphine-tolerant rats shows antiopiate properties in guinea pig ileum bioassay.

The existence of an endogenous antiopiate system which counteracts endogenous opiate effects has been proposed. The present study set out to seek substance/s with morphine-antagonist activity in the brain and serum of morphine-tolerant rats. Cerebral extracts were partly purified on Sephadex G 25 and serum was ultrafiltered through membranes with pore diameter smaller than 0.005 micron. On the guinea pig ileum myenteric plexus longitudinal muscle a fraction of the cerebral extract and the serum ultrafiltrate in toto did increase electrically induced contractions, and antagonized the depressant effect of morphine. The serum ultrafiltrate also enhanced longitudinal smooth muscle tone. Preliminary findings suggest that levels of endogenous morphine-antagonist substance/s are higher in morphine-tolerant rats than in controls. Only cerebral extract, not serum ultrafiltrate, inhibited [3H]-naloxone binding to cerebral opiate receptors. In the guinea pig bioassay both the cerebral extract and serum ultrafiltrate antagonized, to some extent, the inhibition elicited by morphine, norepinephrine and adenosine. These observations support the existence of endogenous compound/s which may be functional antagonist/s of opiates and play a role in the development of tolerance and dependence.

Animals↗
PubMed1987

Binding studies of dermorphin and its L-form on rat brain opioid receptors.

It is well known dermorphin is a potent and long-acting opioid peptide while its synthetic L-form is almost completely devoid of biological activity. We investigated whether the L-Ala2 residue might affect the affinity of the compound for opioid receptors or make [L-Ala2] dermorphin more sensitive to metabolic degradation. Dermorphin and [L-Ala2] dermorphin were assayed in [3H]naloxone binding to opioid receptors in rat brain preparations in the absence and presence of peptidase inhibitors bestatin, captopril and thiorphan. The synthetic [L-Ala2] dermorphin showed very low affinity for the opioid receptors. This was only slightly increased in the presence of the peptidase inhibitor bestatin, alone and in combination with captopril and thiorphan. The low affinity of [L-Ala2] dermorphin was not improved even when the binding assay was carried out at 0 degrees C. We suggest that the D-Ala2 residue is essential for the binding of dermorphin to the opioid receptors as well as for its pharmacological activity.

Alanine↗
PubMed1986

[Radiotherapy of inoperable, loco-regional epidermoid carcinoma of the lung. 5-year experience].

Results of chest radiotherapy on 48 patients with inoperable squamous-cell carcinoma are reported; 25 patients had continuous treatment whereas the remaining 23 patients had split-course. Objective remission was obtained in 71% of the cases; mean survival was 11.7 months for the whole series, and 14 months for responders. An advantage in objective remission rate for patients having a dose of 60 Gy or more was found. Split-course resulted in similar survival and objective remission rate but was less toxic than continuous treatment. In 43% of cases the disease progressed only loco-regionally. Radiotherapy was interrupted because of toxicity in 23% of cases and there was only a case of life-threatening toxicity.

Carcinoma, Squamous Cell↗
PubMed1984

[Palliative radiotherapy of bone metastases. Comparison between 2 fractionations].

One hundred and twenty two symptomatic osseous metastases in 74 patients were treated with palliative irradiation, using two dose/time treatment plans. Pain relief was obtained in 92% of valuable cases (complete response in 68% and improvement in 24%). The complete responses were obtained in 4 weeks in 64% of responsive patients. The median duration of response was 166 days. In advanced cancer patients the short course radiotherapy achieved the same quality and duration of pain relief as conventional treatment.

Bone Neoplasms↗